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[(am)19.7(m)12.3(a)0(t)16.9(o)0(r)22.6(y)-359.6(d)12.8(i)0(s)21.3(e)0(a)17.5(s)11.9(es)16.1(,)-354.9(i)0(n)19.2(c)0(l)21.5(u)0(d)19.5(i)0(n)19.2(g)-359.6(r)11.9(h)11.8(eu)17(m)12.3(a)0(t)22.9(o)0(i)20(d)-357.2(ar)19.2(th)21.4(ri)15.3(t)15.5(i)0(s)-348.7(\()0(R)20.1(A)0(\))21.5(,)]TJ -3.0196 -1.2114 TD 0.0368 Tc [(ank)-5.3(y)5.5(los)-5(i)4.4(ng)-549.5(spo)5.7(n)-1.1(dylitis)-548.1(\()-2.1(AS\),)-550.8(ju)]TJ 14.1433 0 TD 0.037 Tc [(venile)-549.6(i)4.6(d)-4(iopathic)-549.6(arthritis)]TJ -14.1433 -1.2055 TD 0 Tc [(\(JIA\))10.9(,)-504.1(syst)14(emic)-495(lupus)-499.5(eryt)12.3(hema)11.8(tosu)15(s)-507.3(\(SL)11.2(E\),)-500.2(dif)68.4(fere)13(nt)-505.7(type)13.1(s)-507.3(o)0(f)]TJ 0 -1.2114 TD 0.0167 Tc [(vasculi)-3.8(t)2.4(is,)-529.2(s)-1.2(arc)-2.9(o)3.5(i)-3.8(d)-0.4(osis,)-529.2(f)3.4(a)-5.8(m)-0.8(ilial)-527(M)-5.4(edi)-3.8(t)2.4(e)-2.9(rrane)-2.9(an)-528.4(feve)-2.9(r)-526.4(\()1.6(FM)-5.4(F\),)]TJ T* 0 Tc [(seconda)-10.6(ry)-508.8(amylo)-7.7(idosis,)-515.7(etc.,)-518.7(especially)-521.7(in)-511.9(the)-511.5(er)-7.7(a)-511.9(o)0(f)-509.9(biologic)]TJ T* [(im)21.7(mu)19.1(no)20.5(su)18.7(pp)19.5(r)11.9(e)0(s)16.1(s)11.9(iv)19.8(e)-288.2(t)0(h)21.4(e)0(r)16.1(a)13.3(py)17.2(.)]TJ 1.2651 -1.2114 TD [(The)-468(aim)-466.3(of)-474.1(this)-464.6(review)-470.4(is)-474(to)-463.1(give)-472.8(a)-470.1(brief)-466.6(insight)-470.7(into)-473.8(the)]TJ -1.2651 -1.2114 TD [(complex)-306(network)-303.5(of)-301.1(the)-296.6(multiple)-304.3(SAA)-300.4(roles)-302.1(in)-303(the)-302.6(pathogenesis)]TJ 0 -1.2055 TD [(of)-229.5(in)]TJ /F12 1 Tf 1.8261 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammation,)-234.3(as)-231.4(well)-233.1(as)-237.4(to)-230.4(summarize)-235.9(and)-232.6(discuss)-235.5(the)-236.9(current)]TJ -2.3572 -1.2114 TD [(evidences)-251(of)-247.4(its)-243.7(clinical)-249.3(utility)-249.9(in)-243.3(assessing)-251.3(an)-245.4(early)-247.2(diagnosis)-252.6(and)]TJ 27.4512 67.6672 TD [(monitoring)-230.2(the)-225(disease)-230.7(activity)-228.1(and)-226.7(response)-232.9(to)-224.4(therapy)-230.4(in)-225.4(a)-225.4(wide)]TJ 0 -1.2114 TD [(range)-302.4(of)-301.1(IRD.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 667.2754 Tm [(LITERATURE)-305.2(REVIEW)]TJ /F11 1 Tf 9.5 0 0 9.5 306.1417 647.2628 Tm [(A)-220.1(comprehensive)-228.2(literature)-224.1(review)-219.8(was)-222.8(conducted)-223.3(using)-220.2(PubMed)]TJ T* [(and)-322.1(Scopus)-321.2(databases)-316.8(to)-319.9(identify)-323.7(articles)-318.1(exploring)-322.8(the)-320.5(role)-320(and)]TJ 0 -1.2055 TD [(utility)-351.4(of)-354.8(SAA)-348.1(in)-350.8(IRD,)-355.8(according)-354.9(to)-349.8(the)-350.3(published)-356.1(guidance)-352.8(on)]TJ 0 -1.2114 TD [(narrative)-317.9(reviews)-315.3(\()]TJ 0 0 0 0.7 k 7.5133 0 TD (8)Tj 0 0 0 1 k 0.4774 0 TD [(\).)-316.2(We)-316.8(used)-316.4(search)-318.6(terms)-314.1(of)]TJ /F13 1 Tf 11.2431 0 TD ()Tj /F11 1 Tf 0.3939 0 TD [(serum)-316.9(amyloid)]TJ -19.6276 -1.2114 TD (A)Tj /F13 1 Tf 0.6863 0 TD ()Tj /F11 1 Tf 0.3939 0 TD (,)Tj /F13 1 Tf 0.4595 0 TD ()Tj /F11 1 Tf 0.3939 0 TD [(serum)-239.3(biomarkers)]TJ /F13 1 Tf 7.2268 0 TD ()Tj /F11 1 Tf 0.3939 0 TD (,)Tj /F13 1 Tf 0.4535 0 TD ()Tj /F11 1 Tf 0.3939 0 TD [(markers)-239.1(of)-235.4(in)]TJ /F12 1 Tf 5.3172 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (ammation)Tj /F13 1 Tf 4.1057 0 TD ()Tj /F11 1 Tf 0.3939 0 TD (,)Tj /F13 1 Tf 0.4535 0 TD ()Tj /F11 1 Tf 0.3939 0 TD (rheumatic)Tj -21.597 -1.2114 TD 0.028 Tc [(diseas)4.1(e)]TJ /F13 1 Tf 2.9719 0 TD 0 Tc ()Tj /F11 1 Tf 0.4237 0 TD (,)Tj /F13 1 Tf 0.7698 0 TD ()Tj /F11 1 Tf 0.4237 0 TD 0.027 Tc (autoin)Tj /F12 1 Tf 2.7272 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0288 Tc [(amma)6.3(tory)-521.7(disease)]TJ /F13 1 Tf 7.8415 0 TD 0 Tc ()Tj /F11 1 Tf 0.9489 0 TD 0.0272 Tc (and)Tj /F13 1 Tf 2.1126 0 TD 0 Tc ()Tj /F11 1 Tf 0.4177 0 TD 0.0295 Tc [(CO)4.6(VI)4.4(D-19)]TJ /F13 1 Tf 4.6906 0 TD 0 Tc ()Tj /F11 1 Tf 0.9489 0 TD 0.0265 Tc (in)Tj -24.8314 -1.2114 TD 0 Tc [(dif)62.5(ferent)-331.6(combinations.)-328.6(The)-324.8(latter)-328(term)-326(was)-324.2(added)-332.1(since)-324.4(we)-327.3(are)]TJ T* [(currently)-307.7(experiencing)-306.9(a)-303(pandemic)-309.1(of)-307.1(Coronavirus)-305.5(disease)-308.3(2019)]TJ 0 -1.2055 TD [(\(COVID-19\).)-233.7(Search)-226.5(terms)-230.5(were)-227.6(used)-226.9(as)-231.4(key)-224.4(words)-230.6(and)-226.7(as)-231.4(MeSH)]TJ 0 -1.2114 TD [(terms)-254.4(to)-254.3(maximize)-260.6(the)-254.8(output)-254.2(from)-258.9(the)-254.9(literature.)-256.8(Only)-255.8(available)]TJ T* [(full-text)-272.5(articles)-270.3(in)-273.2(English)-268.5(published)-272.5(until)-275.4(September)-273.7(2020)-268.2(were)]TJ T* [(included)-12.3(.)-498.1(Add)-9.6(itional)-505.5(exclusio)-10.6(n)-503.3(criteria)-511(were)-502.1(stu)-7.5(dies)-504.8(on)-504.6(non-)]TJ T* 0.57 Tc [(h)534.1(u)535(m)534.6(a)535.6(ns)534.2(p)535(e)538.4(c)532.5(i)537.6(e)532.5(s)534.2(,c)532.5(a)535.6(s)540.1(er)534.2(e)538.4(p)535(o)532.9(r)534.2(t)537.8(s)534.2(,r)534.2(e)538.4(v)532.7(i)537.6(e)532.5(w)536.8(s)534.2(,c)532.5(o)538.9(m)534.6(m)534.6(e)532.5(n)538.1(t)531.8(a)535.6(r)534.2(i)537.6(e)532.5(sa)535.6(n)532.1(d)]TJ T* 0 Tc [(stu)-7.5(di)-7.7(es)-503(no)-9.3(t)-503.6(concer)-14.6(ning)-509.5(rhe)-7.9(uma)-9.4(tic)-507.9(di)-7.7(seas)-12.4(es)-503.1(or)-508.6(not)-507(di)-7.7(sc)-7.7(ussin)-9.9(g)]TJ 0 -1.2055 TD [(SAA.)-386.7(The)-390.4(reference)-394.2(lists)-387.6(of)-390.6(the)-386.1(selected)-391.1(articles)-389.7(were)-388.7(reviewed)]TJ 0 -1.2114 TD [(to)-278.1(identify)-282(additional)-281.7(articles)-282.3(meeting)-280.1(the)-278.7(eligibility)-282.6(criteria.)-281(The)]TJ T* [(database)-292.9(search)-294.7(resulted)-291.4(in)-291.1(2675)-292(articles)-294.2(of)-289.1(which)-294.3(300)-287.7(remained)]TJ T* 0.0127 Tc [(af)5.3(te)5(r)-506.5(t)4.4(he)-508.2(r)12.7(e)-7(mo)5.4(v)5.2(a)2.1(l)-507.1(o)-0.5(f)-507.9(d)12.7(upli)4.2(c)5(a)2.1(te)5(s)-506.5(a)]TJ 14.3582 0 TD 0.0096 Tc [(nd)-514.7(title/abstract)-511.9(screening.)]TJ -14.3582 -1.2114 TD 0 Tc [(Finally,)-473.5(after)-475.6(assessing)-484.1(the)-469.7(full-text)-475.4(articles)-479.2(for)-474.2(eligibility)-479.5(and)]TJ T* [(screening)-407.3(of)-396.6(the)-404(reference)-406.1(lists,)-402.3(a)-404.4(total)-399.1(of)-402.5(180)-401(full-text)-403.7(articles)]TJ T* [(were)-317.1(included)-322.6(in)-315(the)-320.5(present)-317.5(review.)-324(The)-318.8(included)-316.6(articles)-324(were)]TJ 0 -1.2055 TD [(divided)-262.6(in)-261.2(two)-263.6(groups:)-266.6(articles)-264.4(reporting)-261.4(on)-265.9(the)-260.8(role)-260.3(of)-265.3(the)-260.8(SAA-)]TJ 0 -1.2114 TD [(related)-213.2(genes)-210(and)-208.8(proteins)-218.1(in)-207.5(the)-207.1(pathogenesis)-214.2(of)-211.6(IRD)-209.8(\(n=72\))-214.9(and)]TJ T* [(ar)-16.6(t)-8.3(i)0(c)-10.3(l)-6.6(e)-7.7(s)-519.2(re)-13.7(po)-12.4(r)-12(t)0(i)-10.9(n)-8(g)-514.7(o)-7.2(n)-515.3(c)-7.7(o)-7.3(r)0(r)-18(e)-7.7(l)-6.6(a)0(t)-12.9(i)-8.5(o)-7.3(n)-8(s)-513.2(b)-7.3(e)-7.7(t)-8.3(we)-11(e)-7.7(n)-515.3(S)-9.4(A)0(A)-523.7(a)0(n)-12.6(d)-518.4(c)-7.7(l)-6.6(i)-8.5(n)-8(ic)-10.3(a)-10.6(l)]TJ T* [(features)-410.9(of)-408.5(various)-415(IRD)-406.7(\(n=102\))-410.3(or)-413.1(COVID-19)-409.6(\(n=6\))-413.4(\()]TJ /F14 1 Tf 0 0 0 rg 22.9516 0 TD (Figure)Tj -22.9516 -1.2114 TD (1)Tj /F11 1 Tf 0 0 0 1 k 0.5013 0 TD [(\).)-381.9(Results)-386.6(from)-384.3(the)]TJ /F12 1 Tf 8.1458 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rst)-384.3(group)-383.1(are)-382.3(summarized)-390.2(in)-386.6(the)]TJ /F13 1 Tf 13.8867 0 TD ()Tj /F11 1 Tf 0.3998 0 TD (SAA-)Tj -23.4648 -1.2114 TD [(related)-434(genes)-430.8(and)-435.5(proteins)]TJ /F13 1 Tf 10.9686 0 TD ()Tj /F11 1 Tf 0.8235 0 TD (and)Tj /F13 1 Tf 1.9335 0 TD ()Tj /F11 1 Tf 0.3939 0 TD [(SAA)-431.7(in)-434.3(rheumatic)-435.7(diseases)]TJ /F13 1 Tf 11.1476 0 TD ()Tj /F11 1 Tf -25.2671 -1.2055 TD [(sections,)-253.3(while)-253.1(results)-254.7(from)-253(the)-254.9(latter)-256.4(group)-251.9(are)-251(summarized)-258.9(in)-255.3(a)]TJ 0 -1.2114 TD 0.0247 Tc [(narrati)4.2(ve)-520.1(man)4.7(n)-1.2(er)-518.4(in)-520.4(each)-524.4(re)5.1(levan)4.7(t)-526.7(se)5.1(cti)4.2(o)-0.5(n)-520.4(o)-0.5(f)-519.8(t)-1.5(hi)4.2(s)-524.4(r)0.8(evi)4.2(e)-0.9(w.)]TJ T* 0 Tc [(Summary)-354.1(tables)-350.8(with)-348.5(characteristics)-360.5(of)-348.8(each)-348.4(article)-353.8(included)-358.4(in)]TJ T* [(each)-300.6(section)-304.2(are)-298.8(provided)-309.1(\()]TJ /F14 1 Tf 0 0 0 rg 10.9268 0 TD [(Tables)-305.7(1)]TJ /F15 1 Tf 0 0 0 1 k 3.497 0 TD ()Tj /F14 1 Tf 0 0 0 rg 0.5132 0 TD (9)Tj /F11 1 Tf 0 0 0 1 k 0.5013 0 TD (\).)Tj /F1 1 Tf 11.9999 0 0 11.9999 306.1417 271.559 Tm [(SAA-RELATED)-302.2(GENES)-303.6(AND)-301.7(PROTEINS)]TJ /F11 1 Tf 9.5 0 0 9.5 306.1417 251.5464 Tm [(Th)23.1(e)-264.3(S)0(A)21.1(A)-261.9(ge)20.6(ne)-248.5(fa)17.8(m)12.3(i)0(l)20.6(y)-264.1(is)-253.2(lo)21.9(ca)23.5(te)19.8(d)-261.8(o)0(n)-248(t)0(h)15.4(e)-258.3(s)11.9(h)0(o)16.5(r)11.9(t)-259(a)0(r)19.2(m)-262.2(of)-247.4(ch)16(r)11.9(o)0(m)23(o)0(s)16.6(o)0(m)23(e)]TJ 0 -1.2114 TD [(1)13.5(1)-326.6(\(1)16.4(1)13.5(p)0(1)20.3(5)0(.)16.7(1)13.5(\).)-316.2(It)-319.8(co)20.9(nt)19.5(a)13.3(i)0(n)19.2(s)-328.3(fo)21.2(ur)-315.5(ge)14.7(ne)20.1(s)11.9(,)-325.1(na)17.2(m)12.3(e)0(l)21.5(y)]TJ /F16 1 Tf 17.9686 0 TD [(SA)21.9(A1)]TJ /F11 1 Tf 2.1961 0 TD (,)Tj /F16 1 Tf 0.543 0 TD [(SA)15.9(A2)]TJ /F11 1 Tf 2.2021 0 TD (,)Tj /F16 1 Tf 0.543 0 TD [(SA)21.9(A3)]TJ /F11 1 Tf -23.4529 -1.2055 TD -0.0133 Tc [(an)-13.3(d)]TJ /F16 1 Tf 1.6709 0 TD 0 Tc [(SA)21.9(A4)]TJ /F11 1 Tf 2.399 0 TD (\()Tj 0 0 0 0.7 k 0.3282 0 TD [(11)15.1(5)]TJ 0 0 0 1 k 1.4084 0 TD [(\).)-185(A)12.7(l)0(l)-180.3(t)0(h)21.4(e)-192.7(ge)20.6(ne)20.1(s)-191(c)0(o)20.9(n)0(s)21.8(i)0(s)15.3(t)-187.3(of)-181.7(4)-189.4(e)0(x)18.7(o)0(n)20.5(s)-191(an)17.2(d)-190.1(3)-189.4(in)19.2(tr)21.5(on)20.5(s,)-181.9(an)17.2(d)]TJ -5.8065 -1.2114 TD [(th)21.4(ei)19.6(r)-244.7(i)0(n)19.2(i)0(t)18.9(i)0(a)22.7(l)-245.3(tr)21.5(an)17.2(s)11.9(c)0(r)22.1(i)0(p)16.1(t)0(s)-235.1(h)11.8(av)17.7(e)-246.4(1)13.5(8)-243.1(a)0(a)-236(s)0(i)21.3(g)0(n)20.3(a)0(l)-238(s)11.9(eq)18.9(ue)17(nc)20.1(e)-246.4(t)15.6(ha)19.1(t)-247(i)0(s)-235.3(r)11.9(em)16.6(ov)21.1(ed)]TJ T* [(in)-189.6(th)21.4(e)-198.7(s)0(e)16.1(r)11.9(um)-189.8(pr)18.7(ot)20.2(ei)19.6(ns)21.8(.)-199.7(W)0(i)16.6(t)0(h)21.4(i)0(n)-189.6(t)0(h)21.4(e)-198.7(SA)15.2(A)-196.2(g)0(e)20.6(n)0(e)-194.8(c)0(l)21.5(u)12.8(st)15.5(er)22.1(,)-199.7(o)0(n)20.5(l)0(y)-193.1(t)15.5(he)]TJ /F16 1 Tf 23.4529 0 TD [(SA)21.9(A1)]TJ /F11 1 Tf -23.4529 -1.2114 TD -0.0133 Tc [(an)-13.3(d)]TJ /F16 1 Tf 1.6829 0 TD 0 Tc [(SA)15.9(A2)]TJ /F11 1 Tf 2.4169 0 TD [(ge)20.6(ne)20.1(s)-208.9(e)0(n)20.1(c)0(o)20.8(d)0(e)-197.9(a)0(n)-197.6(a)0(c)17.5(u)0(t)22.3(e)-210.6(p)12.8(h)0(a)19.1(s)0(e)-198.7(s)11.9(er)16.1(u)12.7(m)-208.5(pr)18.7(ot)20.2(ei)19.6(ns)-199(\(S)23.3(AA)19.3(1)-207.3(a)0(n)17.2(d)]TJ -4.0998 -1.2114 TD [(SA)21.1(A2)-242.4(is)21.3(ot)20.2(yp)17.2(es)22.1(\))-253.8(w)0(i)18(t)0(h)-241.2(a)0(p)20.1(p)0(r)18.7(o)0(x)19.1(i)0(m)21.7(a)0(t)22.9(e)0(l)15.5(y)-252.2(9)13.5(5)0(%)-245(s)11.9(eq)18.9(ue)17(nc)20.1(e)-252.4(i)0(d)22.1(e)0(n)20.1(t)0(i)18.9(t)0(y)20(,)-253.4(wh)20.4(ic)19.6(h)]TJ T* [(a)13.3(r)0(e)-198.7(c)0(o)20.8(o)0(r)16.6(d)12.7(in)19.2(a)13.3(t)0(e)19.8(l)0(y)-199.1(i)0(n)19.2(d)12.7(uc)17(ed)-197.9(i)15.3(n)-210.9(r)11.9(e)0(s)22.1(p)0(o)17.4(n)0(s)21.8(e)-210.6(t)15.5(o)-210.1(in)]TJ /F12 1 Tf 16.2022 0 TD ()Tj /F11 1 Tf 0.5192 0 TD -0.0133 Tc [(am)-13.3(m)5.4(a)-13.3(t)9.6(i)-13.3(o)6.7(n)-224.2(\()]TJ 0 0 0 0.7 k 4.5653 0 TD 0 Tc [(11)15.1(6)]TJ 0 0 0 1 k 1.4084 0 TD (\).)Tj /F16 1 Tf 0.7579 0 TD [(SA)21.9(A3)]TJ /F11 1 Tf -23.4529 -1.2055 TD [(co)20.9(nt)19.5(a)13.3(i)0(n)19.2(s)-447.6(an)-442.3(ea)23.5(rl)17.2(y)-449.1(s)11.9(to)20.2(p)-446.8(c)0(o)20.9(d)0(o)17.4(n)-449.6(s)11.9(u)12.7(gg)14.9(es)22.1(ti)18.9(ng)-439.2(i)15.3(t)-449.9(is)-438.2(a)-446.2(n)0(o)20.5(n)0(-)17.8(t)0(r)21.5(a)0(n)17.2(s)11.9(la)18.6(te)19.8(d)]TJ 0 -1.2114 TD [(p)12.7(s)0(e)16.1(u)12.7(do)17.4(ge)20.6(ne)-224.6(\()]TJ 0 0 0 0.7 k 5.1501 0 TD [(11)21.1(7)]TJ 0 0 0 1 k 1.4084 0 TD [(\).)-226.7(Th)23.1(e)-240.4(c)0(o)20.9(r)11.9(r)11.9(e)0(s)16.1(p)12.7(on)20.5(di)16.1(ng)-224.4(pr)18.7(ot)20.2(ei)19.6(n)-234.8(o)0(f)-229.5(t)15.5(he)]TJ /F16 1 Tf 14.0061 0 TD [(SA)21.9(A4)]TJ /F11 1 Tf 2.4467 0 TD [(ge)20.6(ne)-224.6(is)]TJ -23.0113 -1.2114 TD [(co)20.9(ns)21.8(ti)18.9(tu)22.3(ti)18.9(ve)20.6(ly)-282.6(sy)16.4(nt)19.5(h)11.8(e)0(s)22.1(i)0(z)19.6(e)0(d)17(,)-295.2(m)12.3(e)0(a)17.5(n)0(i)19.2(n)0(g)-284.1(i)0(t)-279.4(i)0(s)-289.1(n)0(o)20.5(t)-294.8(i)15.3(n)0(d)16.7(u)12.7(ce)14.4(d)-291.6(i)0(n)-285.1(t)0(h)21.4(e)-294.2(ac)17.5(u)12.7(t)0(e)]TJ T* [(p)12.7(h)0(a)19.1(s)0(e)-419.5(r)11.9(es)22.1(po)17.4(ns)21.8(e)-425.4(\()]TJ 0 0 0 0.7 k 6.827 0 TD -0.0135 Tc [(11)-13.5(8)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc [(\).)-417.7(Th)17.1(e)-419.5(i)0(n)19.2(d)0(u)19.5(c)0(i)19.6(b)0(l)21.9(e)-425.4(SA)15.2(A)-423(i)0(s)21.3(o)0(f)21.2(o)0(r)16.6(m)12.3(s)11.9(,)-426.5(SA)21.1(A1)-415.4(an)17.2(d)]TJ -8.2294 -1.2114 TD [(SA)21.1(A2)20.2(,)-289.2(a)0(r)19.2(e)-288.2(te)19.8(rm)18.3(ed)-281.4(a)13.3(c)0(u)17(t)0(e)19.8(-)0(p)20.6(h)11.8(as)19.2(e)-294.1(S)14.5(AA)19.3(.)]TJ 1.2651 -1.2114 TD [(SAA)-306.4(has)-315.1(sev)14.6(era)17.5(l)-322.9(a)0(l)12.6(lel)14.9(ic)-314.6(var)11.7(ian)14.6(ts)-318.7(\()]TJ /F17 1 Tf 13.1467 0 TD (a)Tj /F11 1 Tf 0.6206 0 TD (,)Tj /F17 1 Tf 0.5371 0 TD (b)Tj /F11 1 Tf 0.5371 0 TD (,)Tj /F17 1 Tf 0.5431 0 TD (g)Tj /F11 1 Tf 0.7221 0 TD (in)Tj /F16 1 Tf 1.116 0 TD (SAA1)Tj /F11 1 Tf 2.5482 0 TD [(an)11.2(d)]TJ /F17 1 Tf 1.8082 0 TD (a)Tj /F11 1 Tf 0.6206 0 TD (,)Tj /F17 1 Tf 0.5371 0 TD (b)Tj /F11 1 Tf 0.8593 0 TD (in)Tj /F16 1 Tf -24.8613 -1.2114 TD [(SAA)15.5(2)]TJ /F11 1 Tf 2.22 0 TD [(\).)-274.5(Two)-267.8(sin)13.2(gle)-272.4(nu)10.7(cle)13.8(oti)11.7(de)-275.4(po)11.5(lym)16.1(orp)11.4(his)15.2(ms)-274.2(\(S)11.3(NPs)11.9(\))-283.6(w)0(i)12(thi)12.8(n)-276.6(the)]TJ -2.22 -1.2055 TD [(exo)17.4(n)-479.5(3)-475.8(of)-468.2(the)]TJ /F16 1 Tf 6.3138 0 TD [(SAA)15.5(1)]TJ /F11 1 Tf 2.6974 0 TD [(gen)12.6(e)-473.2(gen)12.6(era)11.5(te)-469.6(thr)15.4(ee)-469(com)15.3(mon)-468.4(iso)14(for)15.2(mes)16.5(:)]TJ -9.0112 -1.2114 TD [(SAA)15.9(1)]TJ /F17 1 Tf 2.3035 0 TD (a)Tj /F11 1 Tf 1.0264 0 TD [(\(52)17.9(Val)11.4(in)13.3(e/5)11.5(7)-404.2(A)0(l)12(a)0(n)11.2(ine)11.5(\),)-393.8(SAA1)]TJ /F17 1 Tf 11.8876 0 TD (b)Tj /F11 1 Tf 0.9429 0 TD [(\(52)12(Al)12(an)11.2(ine)11.5(/57)-391(Al)12(anin)18.5(e\))]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT /F6 1 Tf 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -16.83 0 TD (2)Tj ET endstream endobj 24 0 obj<>stream Hbd`ad`ddprvL)I23M4Os62Jf!#[ ?O~ D1q4RpLOJU,.I-VK/*/J,IMSpQL()VJ-N-* )())d) RR28ANa1G SD endstream endobj 25 0 obj<> endobj 26 0 obj<> endobj 27 0 obj<> endobj 28 0 obj<> endobj 29 0 obj<> endobj 30 0 obj<> endobj 31 0 obj<> endobj 32 0 obj<> endobj 33 0 obj<> endobj 34 0 obj<> endobj 35 0 obj<> endobj 36 0 obj<> endobj 37 0 obj<> endobj 38 0 obj<> endobj 39 0 obj<> endobj 40 0 obj<> endobj 41 0 obj<> endobj 42 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 43 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 44 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 45 0 obj<>/Font<>/ProcSet[/PDF/Text/ImageC]/ExtGState<>>> endobj 46 0 obj<>stream /GS1 gs BT /F11 1 Tf 9.5 0 0 9.5 45.3543 288.7369 Tm 0 0 0 1 k 0.0164 Tc 0 Tw [(and)-519.9(S)1(AA1)]TJ /F17 1 Tf 4.4519 0 TD 0 Tc (g)Tj /F11 1 Tf 0.9369 0 TD 0.0167 Tc [(\(5)6.4(2Ala)6.1(nine/57)-518.8(V)-2.4(aline\).)-517.2(S)1.3(ome)-516.2(o)3.5(f)-521.8(t)2.4(hese)-516.2(variants)]TJ -5.3888 -1.2055 TD 0 Tc [(con)12.8(tri)18.9(but)15.1(e)-312.1(t)0(o)-296.1(the)-296.6(sus)12.7(cept)18.9(ibi)11.5(lit)18.3(y)-305.9(t)0(o)-302(A)0(A)-302.9(amy)12.2(loi)19.4(dos)11.4(is.)-297.8(In)-301.6(par)14.1(ti)13(cula)17.7(r,)]TJ /F16 1 Tf 0 -1.2114 TD [(SAA)15.5(1)]TJ /F18 1 Tf 2.22 0 TD (a)Tj /F11 1 Tf 0.9966 0 TD [(al)12.7(lel)14.9(e)-377.7(i)0(s)-366.6(a)-374.6(ris)15.3(k)-376.3(f)0(a)11.9(cto)12.5(r)-370(for)-366.8(de)11(vel)14(op)11.5(ing)-364.2(AA)-368.6(amy)12.2(loi)13.4(do)11.5(sis)-366.7(in)]TJ -3.2166 -1.2114 TD [(Cau)13.7(ca)11.6(sia)10.7(n)-264.6(\()]TJ 0 0 0 0.7 k 4.6369 0 TD (119)Tj /F13 1 Tf 0 0 0 1 k 1.4203 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5072 0 TD (121)Tj 0 0 0 1 k 1.4203 0 TD [(\).)-268.5(Con)20.1(tra)10.9(ril)14.7(y,)-260.9(in)-267.2(the)-254.9(Jap)13.9(anes)15.4(e)-270.3(p)0(o)11.5(pul)12.9(ati)14.3(on)-260(thi)12.9(s)]TJ -7.9847 -1.2114 TD [(al)12.7(lel)14.9(ic)-231.1(var)11.8(ian)14.6(t)-235.1(has)-225.6(pro)11.4(te)13.8(cti)11.2(ve)-230(pro)11.4(pe)11(rti)12.9(es,)-225.4(whi)17.9(le)]TJ /F16 1 Tf 17.9805 0 TD [(SAA)15.5(1)]TJ /F18 1 Tf 2.214 0 TD (g)Tj /F11 1 Tf 0.6445 0 TD [(al)12.7(lel)14.9(e)-234.5(car)11.5(rie)13.6(s)]TJ -20.8391 -1.2114 TD [(a)-195.6(hig)13.7(her)-186.9(ris)15.3(k)-197.3(o)0(f)-193.7(d)0(e)11(vel)14(op)11.5(ing)-191.1(AA)-189.5(amy)12.2(lo)16(ido)14.9(sis)-187.6(\()]TJ 0 0 0 0.7 k 17.2764 0 TD (122)Tj /F13 1 Tf 0 0 0 1 k 1.4203 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5073 0 TD (124)Tj 0 0 0 1 k 1.4203 0 TD [(\).)-190.9(Blan)14.7(k)-197.3(e)0(t)-189.1(a)0(l)12.7(.)]TJ -20.6242 -1.2114 TD (\()Tj 0 0 0 0.7 k 0.3402 0 TD (119)Tj 0 0 0 1 k 1.4203 0 TD [(\))-373.1(rep)17(ort)14.2(ed)-365(a)-374.6(100)16.7(%)-371.9(i)0(n)13.3(cide)12.7(nc)14.1(e)-371.7(o)0(f)]TJ /F16 1 Tf 13.0811 0 TD [(SAA)15.5(1)]TJ /F18 1 Tf 2.22 0 TD (a)Tj /F16 1 Tf 0.6206 0 TD (/)Tj /F18 1 Tf 0.3044 0 TD (a)Tj /F11 1 Tf 0.9966 0 TD [(gen)12.6(ot)14.3(ype)-366.5(am)13.7(ong)]TJ -18.9831 -1.2114 TD [(pat)11.8(ients)-486.2(with)-491.8(idio)12.3(pat)11.8(hic)-493.8(AA)-493.9(amyl)11.5(oidso)13.5(sis.)-488.8(More)10.7(ove)13.4(r,)-498.1(anot)13.6(her)]TJ 0 -1.2055 TD [(SNP)-510.7(in)-511.9(the)]TJ /F16 1 Tf 5.353 0 TD [(SA)-7.9(A1)]TJ /F11 1 Tf 2.7511 0 TD [(g)-7.5(ene)-512.8(at)-508.2(posi)-9(tion)-509.6(-13)-514.1(in)-511.9(the)-511.5(5)]TJ /F13 1 Tf 12.7409 0 TD ()Tj /F11 1 Tf 0.7281 0 TD [(re)-7.7(gulat)-8.3(ory)]TJ -21.5731 -1.2114 TD [(reg)14.6(ion)-286.4(\(pr)15.6(omo)15.7(ter)-290.6(reg)14.6(io)14(n\),)-288.5(is)-289.1(ass)13.2(oci)12.3(ate)15.2(d)-297.6(w)0(i)12(t)0(h)-288.9(the)-284.7(AA)-291(amy)12.2(loi)13.4(do)11.5(sis)]TJ T* 0.0381 Tc [(occurrence)-542.5(in)-542.8(both)-546.9(J)2(apanese)-548.5(a)3.7(nd)-545.9(Caucasian)-542.8(r)2.3(heumatoid)]TJ T* 0.0143 Tc [(arthri)5.8(tisnbsp;patients,)-519.6(w)-0.9(hich)]TJ 12.5321 0 TD 0.0141 Tc [(might)-519.4(e)0.4(xplain)-519.1(the)-518.8(d)-3(iscrepancy)]TJ -12.5321 -1.2114 TD 0 Tc [(bet)12.5(we)12.9(en)-326(pre)11(vi)13.8(ous)-322.8(rep)11(ort)20.2(s)-334.2(\()]TJ 0 0 0 0.7 k 10.7418 0 TD [(12)15.1(5)]TJ 0 0 0 1 k 1.4203 0 TD (,)Tj 0 0 0 0.7 k 0.549 0 TD (126)Tj 0 0 0 1 k 1.4203 0 TD [(\).)-328.2(Th)11.1(e)-330(lat)16.3(ter)-320.4(SNP)-325.7(al)12.7(so)-323.6(af)71.6(fec)13(ts)]TJ -14.1314 -1.2114 TD 0.0166 Tc [(the)-522.2(S)-4.7(AA)-519.8(tran)-3.4(scri)-3.9(pti)-3.9(o)3.4(n)-522.5(w)1.4(i)-3.9(t)2.3(h)-526.6(t)2.3(he)-522.2(-13T)-521.2(allele)-522.2(hav)-2.8(i)2.1(n)-3.4(g)-522(gre)-3(a)0.1(te)-3(r)]TJ 0 -1.2055 TD 0 Tc [(ac)11.6(tiv)11.5(it)13(y)-293.9(\()]TJ 0 0 0 0.7 k 3.4911 0 TD (127)Tj 0 0 0 1 k 1.4203 0 TD (\).)Tj -3.6462 -1.2114 TD [(S)14.5(A)0(A)-422.3(t)0(r)15.5(a)13.3(ns)21.8(cr)16.1(ip)22.1(ti)18.9(on)-421.1(ca)17.5(n)-431.7(b)0(e)-420.8(u)12.8(p-)20.6(re)16.1(gu)23.2(la)18.6(te)19.8(d)-428.9(b)0(y)-420.5(s)0(e)16.1(v)0(e)20.6(r)11.9(al)-423(cy)20.6(to)20.2(k)11.6(i)0(n)19.2(e)0(s)]TJ -1.2651 -1.2114 TD [(in)19.2(cl)21.5(ud)19.5(in)19.2(g)-228.3(t)0(h)21.4(e)-228.5(tu)22.3(mo)17(r)-226.8(n)0(e)20.1(c)0(r)16.1(o)0(s)22.6(i)0(s)-217.4(f)0(a)17.8(c)0(t)19.8(o)0(r)-216.2(a)0(l)18.6(p)12.7(h)11.8(a)-231.4(\(T)20.1(NF)]TJ /F17 1 Tf 18.4699 0 TD (a)Tj /F11 1 Tf 0.6147 0 TD [(\),)-214.8(IL)16.6(-)13.8(1)]TJ /F17 1 Tf 2.4348 0 TD (b)Tj /F11 1 Tf 0.7698 0 TD -0.0133 Tc [(an)-13.3(d)-235.3(I)-13.3(L)9.3(-)-13.3(6)]TJ -22.2892 -1.2114 TD 0 Tc (\()Tj 0 0 0 0.7 k 0.3342 0 TD -0.0135 Tc [(12)-13.5(8)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc [(\).)-292.4(TN)22.2(F)]TJ /F17 1 Tf 2.6974 0 TD (a)Tj /F11 1 Tf 0.925 0 TD -0.0143 Tc [(an)-14.3(d)-302(I)-14.3(L-1)]TJ /F17 1 Tf 3.4314 0 TD 0 Tc (b)Tj /F11 1 Tf 0.8414 0 TD [(a)13.3(c)0(t)19.8(i)0(v)19.8(a)0(t)22.9(e)-300.1(th)21.4(e)-300.1(n)0(u)16.7(c)0(l)21.5(e)0(a)17.5(r)-298.4(fa)23.8(ct)19.8(or)16.6(-)13.8(k)0(a)18.9(p)0(p)19.5(a)-297(B)-300.2(\()0(N)19.8(F)0(-)]TJ /F17 1 Tf -9.6318 -1.2114 TD (k)Tj /F11 1 Tf 0.5311 0 TD [(B\))-333.2(s)11.9(i)0(t)18.9(e)0(.)-332.8(I)0(L)22.6(-)0(6)-336.7(b)0(i)20(n)0(d)22.6(s)-346.1(to)-331.9(a)-338.8(t)0(r)15.5(a)13.3(ns)21.8(me)16.6(m)12.3(b)0(r)16.6(a)13.3(ne)-332(G-)17.7(co)20.9(up)19.5(le)21.5(d)-345.3(p)12.7(ro)16.6(te)19.8(in)-332.9(1)13.5(3)0(0)]TJ -0.5311 -1.2114 TD [(\(g)19.2(p)12.7(1)0(3)21.1(0)0(\))-228.3(l)0(e)15.5(a)13.3(di)22.1(ng)-230.3(to)-230.4(t)15.6(h)0(e)-228.6(a)0(c)17.5(t)0(i)18.9(v)0(a)23.7(t)0(i)18.9(o)0(n)-224.1(o)0(f)-229.5(J)0(a)19(n)0(u)16.7(s)-232.8(ki)15(na)23.2(se)-228.5(2)-237.1(\()0(J)20.5(A)0(K)16.2(-)13.8(2\))16.4(,)-235.5(w)0(h)20.4(i)0(c)19.6(h)]TJ 27.4512 22.9993 TD [(r)11.9(e)0(s)16.1(u)12.8(lt)20.9(s)-244.7(i)0(n)-231.4(t)0(h)21.4(e)-246.4(r)11.9(e)0(c)20.4(r)0(u)18.7(i)0(t)18.9(m)12.3(en)20.1(t)-247(o)0(f)-229.5(t)0(h)21.4(e)-246.4(s)11.9(i)0(g)19.8(n)0(a)17.2(l)-239.3(tr)21.5(an)17.2(s)11.9(d)0(u)19.5(c)0(e)20.4(r)-244.7(an)17.2(d)-243.9(a)13.3(ct)19.8(iv)19.8(a)13.3(t)0(o)20.2(r)-244.7(of)]TJ 0 -1.2055 TD [(tr)21.5(an)17.2(s)11.9(c)0(r)22.1(i)0(p)16.1(t)0(i)24.9(o)0(n)-355.4(3)-362.4(\(S)23.3(TA)18(T3)18.8(\),)]TJ /F12 1 Tf 10.3121 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(na)17.2(ll)22.6(y)-365.5(r)11.9(es)22.1(ul)18.1(ti)18.9(ng)-349.7(in)-350.8(an)-352.8(im)15.7(p)12.7(r)11.9(es)16.1(s)11.9(i)0(v)19.8(e)-365.8(S)14.5(A)0(A)]TJ -10.8313 -1.2114 TD [(ge)20.6(ne)-212.7(tr)21.5(an)17.2(s)11.9(c)0(r)16.1(i)15.3(pt)16.4(io)20(n)-222.9(\()]TJ 0 0 0 0.7 k 7.6267 0 TD [(12)15.1(9)]TJ 0 0 0 1 k 1.4084 0 TD (,)Tj 0 0 0 0.7 k 0.4416 0 TD [(13)21.1(0)]TJ 0 0 0 1 k 1.4084 0 TD [(\))14.8(.)-223.6(Ho)18.7(we)18.8(ve)20.6(r)11.9(,)-223.6(a)-225.4(w)14.6(ea)17.5(k)-221.1(e)0(x)18.7(p)12.7(re)16.1(s)11.9(s)0(i)21.3(o)0(n)-212.2(o)0(f)-217.5(S)14.5(AA)]TJ -10.885 -1.2114 TD [(m)12.3(e)0(s)16.1(s)11.9(en)20.1(ge)20.6(r)-256.6(R)0(N)16.2(A)-255.9(\()14.8(m)0(R)17.6(N)0(A)17.6(\))-253.8(is)-247.3(in)19.2(d)12.7(u)0(c)17(e)0(d)-245.6(b)0(y)-247.5(t)0(h)21.4(e)-252.4(st)15.5(im)21.7(u)12.7(l)0(a)18.6(t)0(i)18.9(o)0(n)-242(w)0(i)18(t)0(h)-247.2(I)0(L)22.6(-)0(6)]TJ T* [(a)13.3(l)0(o)16(n)0(e)20.1(,)-229.6(w)14.6(h)0(e)16(r)11.9(ea)17.5(s)-226.8(a)0(l)18.6(m)12.3(os)16.6(t)-229.1(n)0(o)-218.2(e)0(x)18.7(p)12.7(r)11.9(e)0(s)16.1(s)11.9(io)20(n)-228.8(i)0(s)-223.4(i)0(n)19.2(d)12.7(uc)17(ed)-215.8(by)-223.6(t)15.6(h)0(e)-222.7(s)11.9(ti)18.9(m)12.3(u)0(l)18.1(a)0(t)22.9(i)0(o)20(n)]TJ T* [(wi)23.9(th)-390.4(TN)22.2(F)]TJ /F17 1 Tf 3.9804 0 TD (a)Tj /F11 1 Tf 1.0205 0 TD [(or)-389.2(IL)22.6(-1)]TJ /F17 1 Tf 2.9122 0 TD (b)Tj /F11 1 Tf 0.9369 0 TD [(al)18.6(on)20.5(e.)-386.5(On)-390.9(th)21.4(e)-395.6(o)0(t)20.2(h)11.8(er)-389.7(h)11.8(a)0(n)17.2(d)0(,)-389.9(t)0(h)21.4(e)-395.6(sy)16.4(ne)20.1(r)11.9(g)0(i)19.8(s)11.9(ti)18.9(c)]TJ -8.85 -1.2114 TD [(in)19.2(d)12.7(u)0(c)17(t)0(i)18.9(o)0(n)-295.8(o)0(f)-295.1(S)0(A)21.1(A)-309.6(m)12.3(R)0(N)16.2(A)-303.6(h)11.8(a)0(s)-297.1(b)0(e)14.9(e)0(n)-296.2(o)0(b)21.3(s)11.9(er)16.1(ve)20.6(d)-303.5(b)0(y)-295.2(a)-309(co)20.9(-s)19.8(ti)18.9(m)12.3(u)0(l)18.1(a)13.3(ti)18.9(on)]TJ T* [(wi)23.9(th)-211.3(IL)16.6(-)13.8(6)-219.2(an)17.2(d)-220(T)0(N)22.2(F)]TJ /F17 1 Tf 7.388 0 TD (a)Tj /F11 1 Tf 0.8414 0 TD [(or)-210.2(IL)22.6(-1)]TJ /F17 1 Tf 2.7332 0 TD (b)Tj /F11 1 Tf 0.7579 0 TD (\()Tj 0 0 0 0.7 k 0.3342 0 TD [(13)21.1(1)]TJ 0 0 0 1 k 1.4084 0 TD [(\))14.8(.)-223.6(It)-206.4(se)16.1(em)22.5(s)-220.8(t)0(h)21.4(a)0(t)-209.9(t)0(h)21.4(e)-222.5(a)13.3(c)0(t)19.8(i)0(v)19.8(a)0(t)16.9(i)0(o)20(n)-216.9(of)]TJ -13.463 -1.2055 TD [(ST)19.8(A)12.7(T)0(3)-184.1(b)0(y)-181.8(a)0(n)-185.7(I)0(L)22.6(-)0(6)-187.5(s)11.9(ti)18.9(m)12.3(u)0(l)18.1(a)13.3(te)19.8(d)-196.1(J)11.7(AK)-186.7(is)-181.6(es)16.1(s)11.9(e)0(n)20.1(t)0(i)18.9(a)13.3(l)-191.6(f)0(o)15.2(r)-191(th)21.4(e)-192.7(p)0(r)18.7(o)0(d)17.4(u)12.7(ct)19.8(io)20(n)-193(o)0(f)]TJ 0 -1.2114 TD [(SA)21.1(A)-405.1(a)0(n)17.2(d)-399(th)15.4(e)-401.6(s)11.9(up)19.5(pl)18.1(em)22.5(en)20.1(ta)16.9(ti)18.9(on)-391.2(of)-396.6(NF)23.7(-)]TJ /F17 1 Tf 15.4741 0 TD (k)Tj /F11 1 Tf 0.5311 0 TD [(B)-401.7(a)0(c)17.5(t)0(i)18.9(v)0(i)25.7(t)0(y)-397.7(s)11.9(ti)18.9(m)12.3(u)0(l)18.1(a)13.3(te)19.8(d)-405(b)0(y)]TJ -16.0053 -1.2114 TD (TNF)Tj /F17 1 Tf 1.8738 0 TD (a)Tj /F11 1 Tf 1.1279 0 TD [(or)-508.6(IL-1)]TJ /F17 1 Tf 3.0674 0 TD (b)Tj /F11 1 Tf 1.0503 0 TD [(strengthens)-503.4(the)-505.5(SAA)-509.3(expression)-507.4(\()]TJ 0 0 0 0.7 k 14.2687 0 TD (132)Tj 0 0 0 1 k 1.4322 0 TD [(\).)-513.2(This)]TJ -22.8203 -1.2114 TD [(ev)20.6(id)22.1(en)20.1(ce)-385.4(is)-390.5(i)15.3(m)0(p)19.1(o)0(r)16.6(t)0(a)22.9(n)0(t)-386.3(f)0(o)21.2(r)-393.9(th)21.4(e)-395.6(t)0(h)21.4(e)0(r)16.1(a)13.3(pe)17(u)12.7(t)0(i)18.9(c)-395.6(ef)80.4(fe)20.7(ct)19.8(s)-393.9(o)0(f)-384.6(m)12.3(on)20.5(oc)20.8(lo)16(na)23.2(l)]TJ T* [(an)11.2(ti)18.9(bod)16.1(ie)13.6(s:)-486.2(JA)12.4(K)-497.7(i)0(n)13.3(hib)19.9(it)13(or)16.6(s)-501.3(\()0(t)18.4(ofa)16.6(ci)13.6(ti)13(ni)13.3(b\))-487.8(an)11.2(d)-494.5(a)0(n)11.2(t)0(i)13(-)0(I)12.7(L)11.8(-6)-491.8(re)16.1(cep)15.2(to)14.3(r)]TJ T* 0.021 Tc [(anti)-5.5(bodi)-5.4(e)1.4(s)-534(\()0(to)-4.2(cilizumab)-529.3(a)-1.5(n)-4.9(d)-533.2(sarilumab)-4.2(\))-531.1(almo)-4.2(st)-536.3(complete)-4.6(ly)]TJ 0 -1.2055 TD 0 Tc [(inhi)10.6(bit)-495.6(the)-499.5(expre)11.8(ssion)-495.3(of)-498(the)-499.5(SAA)-503.3(mRN)10.7(A,)-503.4(wher)12.7(eas)-501.7(the)-499.5(IL-1)]TJ 0 -1.2114 TD 0.0299 Tc [(an)-8(ta)-4.5(gonists)-543(\()-3.1(a)-4.5(n)-2(ak)-6.3(inr)-5.9(a)1.4(\))-546.1(a)-4.5(nd)-542.2(TNF)]TJ /F17 1 Tf 14.5551 0 TD 0 Tc (a)Tj /F11 1 Tf 1.1995 0 TD 0.0284 Tc [(an)-3.5(t)-3.8(i)-4(bod)-6.6(ie)-9.1(s)-544.5(\()-4.6(in)]TJ /F12 1 Tf 6.1944 0 TD 0 Tc ()Tj /F11 1 Tf 0.5669 0 TD 0.032 Tc [(ix)4.7(imab,)]TJ 9.5 0 0 9.5 306.1417 104.7685 Tm 0 Tc [(a)13.3(d)0(a)14.1(l)0(i)20.7(m)12.3(u)12.7(m)0(a)19.7(b)0(,)-398(e)0(t)19.8(a)13.3(ne)20.1(r)11.9(c)0(e)14.4(p)12.7(t\))-393.4(ac)17.5(h)11.8(i)0(e)19.6(v)0(e)-391.1(o)0(n)20.5(l)0(y)-396(a)-404.4(p)12.8(a)0(r)19.2(t)0(i)18.9(a)13.3(l)-406.4(i)0(n)19.2(h)11.8(ib)20(it)18.9(io)20(n)-401.9(\()]TJ 0 0 0 0.7 k 24.0377 0 TD -0.0135 Tc [(10)-13.5(8)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc (,)Tj 0 0 0 0.7 k -25.4401 -1.2114 TD -0.0135 Tc [(13)-13.5(0)]TJ 0 0 0 1 k 1.4084 0 TD 0 Tc [(\))14.8(.)-283.3(Ho)18.7(w)14.6(e)0(v)20.6(e)0(r)16.1(,)-277.3(SA)15.2(A)-279.8(m)12.3(RN)16.2(A)-279.8(t)15.6(ra)19.2(ns)15.8(la)24.6(ti)18.9(on)-271.9(is)-271.2(1)13.5(0)0(-)21.4(f)0(o)21.2(l)0(d)-274.3(l)0(o)21.9(w)0(e)18.8(r)-280.5(th)21.4(a)13.3(n)-282.5(th)21.4(e)]TJ -1.4084 -1.2114 TD [(r)11.9(a)0(t)16.9(e)-419.5(of)-414.5(m)12.3(R)0(N)22.2(A)-423(s)11.9(y)0(n)20.3(t)0(h)15.4(e)0(s)22.1(i)0(s)-408.4(d)0(u)19.5(e)-425.4(to)-409.4(po)17.4(s)11.9(t)0(-)23.4(t)0(r)15.5(a)13.3(ns)21.8(cr)16.1(ip)22.1(ti)18.9(on)20.5(al)-411.1(r)11.9(e)0(g)20.6(u)0(l)18.1(a)0(t)22.9(i)0(o)20(n)0(.)]TJ T* [(SAA)-509.3(mRNA)-507.8(undergoes)-508.1(poly\(A\))-503.5(tail)-505.5(shortening)-509.1(over)-505.9(time,)-510.4(a)]TJ ET 0 0 0 0.7 k 45.354 717.505 m 549.921 717.505 l 549.694 717.222 l 45.581 717.222 l f* 549.921 717.505 m 549.921 315.779 l 549.694 316.063 l 549.694 717.222 l f* 549.921 315.779 m 45.354 315.779 l 45.581 316.063 l 549.694 316.063 l f* 45.354 315.779 m 45.354 717.505 l 45.581 717.222 l 45.581 316.063 l f* q 311.754272 0 0 357.165314 141.732254 342.595123 cm /Im1 Do Q BT /F1 1 Tf 6.9999 0 0 6.9999 50.6268 321.5621 Tm 0 0 0 1 k [(FIGURE)-299.4(1)]TJ /F6 1 Tf 5.0053 0 TD [(|)-429.9(Flow)-301.2(chart)-300.1(illustrating)-306.3(the)-304.1(literature)-299.1(search)-306.7(and)-298.4(study)-301.3(selection)-304.6(process.)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -16.83 0 TD (3)Tj ET endstream endobj 47 0 obj<>stream HKI' 2 Mp!y,^nM+ n]LڳfzHAAWUO2fȪ:?fddͦR[l 2vz G #uA'Np RW׭[f͚U H6׮];4 !DH)cs˺fXh{ Ad%rRA3(ᐼsÇ` 翸|wrC R>{ڱc !B׎@J5ݼy={,8p (__WG110;t۷/M6RJ]; bЪU7n<~3! 9=u !B׎@J5?߿Z\o4A\C}GvwA J)0 64k5 K'O!YZ b)%c t?|ϵA%̣GoJ ,PJ{ֺzhu ȒG%"pQB­(RJi8s*4ltzQ|yw.``>ܶm8*GGAlcǾRJ yGZ2 Q ~ GEࢄ!k-1XFp]JIX8F7! cQ)CAjR a #"pQBµRJip]AYq>8*ԵA JUCa0L+Gy:Y}o5zFLi5zVRV_<+ "8BCꁔ1khsS|StW}YP \b7I,bQ)GAc8! 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-1.3526 TD [(involvement)-304.3(in)-304.4(RA)-296.5(patients)]TJ -47.5662 -1.3607 TD [(Chambers)-305.1(et)-300.5(al.)]TJ 0 -1.3526 TD (\()Tj 0 0 0 0.7 k 0.243 0 TD (14)Tj 0 0 0 1 k 1.1015 0 TD (\))Tj 8.0829 1.3526 TD [(To)-305.3(assess)-295.6(SAA)-303.7(as)-298.8(a)-299.9(marker)-306.1(of)]TJ 0 -1.3526 TD [(disease)-302.4(activity)-302.9(in)-304.4(RA)-296.4(patients)]TJ 17.567 1.3526 TD [(385)-2539.4(RA)-304.6(\(n=185\))]TJ 4.1953 -1.3526 TD [(HC)-306.8(\(n=200\))]TJ 8.2935 1.3526 TD (Radioimmuno-)Tj 0 -1.3526 TD (assay)Tj /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-307.8(a)-299.9(more)-298.6(sensitive)-300(marker)-306.1(of)-299.5(disease)-302.4(activity)-302.9(in)]TJ -1.9195 -1.3526 TD [(RA)-304.6(than)-299.5(CRP)]TJ -47.5662 -1.3607 TD [(Cunnane)-305.9(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.7466 0 TD (15)Tj 0 0 0 1 k 1.1015 0 TD [(\))-1340.3(T)0(o)-305.3(compare)-302.2(SAA)-295.6(with)-303(CRP)-304.1(and)]TJ 1.5793 -1.3607 TD [(ESR)-304.7(in)-296.3(relation)-301.2(to)-307.1(diagnosis)-296(and)]TJ 0 -1.3526 TD [(disease)-302.4(activity)-302.9(in)-304.4(early)]TJ 0 -1.3607 TD (in)Tj /F7 1 Tf 0.7127 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-299.1(arthritis)]TJ 16.4169 4.0739 TD [(140)-2539.4(RA)-304.6(\(n=64\))]TJ 4.1953 -1.3607 TD [(PsA)-303.9(\(n=19\))]TJ 0 -1.3526 TD [(UA)-301.7(\(n=57\))]TJ 8.2935 2.7132 TD (ELISA)Tj /F19 1 Tf 8.0829 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(Compared)-304.5(with)-303(CRP)-304.1(and)-298.4(ESR,)-302(SAA)-295.6(correlates)-307.8(best)]TJ -1.9195 -1.3607 TD [(with)-303(disease)-302.4(activity)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA,)-301(unlike)-303.5(CRP)-296(or)-302.3(ESR,)-302(can)-303.7(be)-303(used)-297.3(for)]TJ -1.9195 -1.3607 TD [(distinguishing)-309.4(patients)-299.9(with)-303(a)]TJ /F7 1 Tf 12.578 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(nal)-296.6(diagnosis)-304.1(of)-299.5(RA)-304.6(in)]TJ -13.0153 -1.3526 TD [(early)-300.8(in)]TJ /F7 1 Tf 2.9805 0 TD ()Tj /F6 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[(disease)-302.4(activity)-302.9(during)-305.5(pregnancy)]TJ 0 -1.3526 TD [(in)-304.4(RA)-296.4(and)-306.5(AS)-297(patients)]TJ 17.8424 2.7132 TD [(52)-2816(RA)-304.6(\(n=11\))]TJ 3.92 -1.3607 TD [(AS)-305.1(\(n=13\))]TJ 0 -1.3526 TD [(HC)-306.8(\(n=28\))]TJ 8.2935 2.7132 TD (Radioimmuno-)Tj 0 -1.3607 TD (assay)Tj /F19 1 Tf 8.0829 1.3607 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-307.8(a)-299.9(reliable)-302.8(marker)-298(of)-299.5(disease)-302.4(activity)-302.9(in)-304.4(RA)-296.4(and)]TJ -1.9195 -1.3607 TD [(AS)-305.1(even)-299.3(during)-305.5(pregnancy)]TJ -47.5662 -2.7132 TD [(Hwang)-299.8(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 5.9286 0 TD (18)Tj 0 0 0 1 k 1.1096 0 TD [(\))-2150.2(T)0(o)-305.3(evaluate)-301.6(use)-302.3(of)-299.5(SAA)-295.6(in)]TJ 2.3892 -1.3526 TD [(monitoring)-305.9(disease)-302.4(activity)-302.9(and)]TJ 0 -1.3607 TD [(therapy)-306.8(response)-299(in)-304.4(RA)-296.4(patients)]TJ 17.567 2.7132 TD [(594)-2539.4(RA)-7002.5(Immunonephelo-)]TJ 6.9999 0 0 6.9999 321.7322 269.1779 Tm [(metric)-301.9(assay)]TJ /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(correlates)-307.8(better)-300.2(than)-307.6(CRP)-296(with)-303(RA)-304.6(disease)]TJ -1.9195 -1.3526 TD [(activity,)-308.3(especially)-301.7(during)-305.5(treatment)-297.5(with)-303(TNF)]TJ /F17 1 Tf 19.0006 0 TD (a)Tj /F6 1 Tf -19.0006 -1.3607 TD (antagonists)Tj -47.5662 -1.3526 TD [(Wild)-298.1(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 4.7299 0 TD (19)Tj 0 0 0 1 k 1.1096 0 TD [(\))-3348.9(T)0(o)-305.3(compare)-302.2(the)-295.9(utility)-303.5(of)-299.5(dif)59.5(ferent)]TJ 3.5879 -1.3607 TD [(biomarkers)-308(as)-298.8(diagnostic)]TJ T* [(indicators)-303.1(of)-299.5(RA)]TJ 17.567 2.7213 TD [(645)-2539.4(RA)-304.6(\(n=364\))]TJ 4.1953 -1.3607 TD [(OA)-304.4(\(n=281\))]TJ 8.2935 1.3607 TD (ELISA)Tj /F19 1 Tf 8.0829 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-307.8(the)-295.9(only)-298.7(biomarker)-309.1(\(among)-301(131)-304(initially)]TJ -1.9195 -1.3607 TD [(considered)-304.7(in)-304.4(the)-296(study\))-305.3(that)-304.6(increases)-299(sensitivity)-305.1(of)-299.5(anti-)]TJ T* [(CCP)-305.5(for)-295.3(RA)-304.5(diagnosis)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(sensitivity)-305.1(and)-298.4(speci)]TJ /F7 1 Tf 8.496 0 TD ()Tj /F6 1 Tf 0.4373 0 TD [(city)-297.2(of)-307.6(SAA)-295.6(are)-304(higher)-302.8(than)]TJ -10.8528 -1.3607 TD [(those)-301.7(of)-299.5(CRP)-304.1(for)-303.4(diagnosing)-299.5(RA)]TJ -47.5662 -1.3526 TD [(De)-303.3(Seny)-297.7(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.5117 0 TD (20)Tj 0 0 0 1 k 1.1015 0 TD [(\))-1575.2(T)0(o)-305.3(compare)-302.2(SAA)-295.6(levels)-305.1(in)-296.3(serum)]TJ 1.8142 -1.3606 TD [(and)-306.5(synovial)]TJ /F7 1 Tf 5.556 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(uid)-307.5(between)-297.6(OA)-304.4(and)]TJ -5.9934 -1.3526 TD [(RA)-304.6(patients)]TJ 17.8424 2.7132 TD [(91)-2816(RA)-304.6(\(n=27\))]TJ 3.92 -1.3606 TD [(OA)-304.4(\(n=29\))]TJ 0 -1.3526 TD [(HC)-306.8(\(n=35\))]TJ 8.2935 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[(metric)-301.9(assay)]TJ /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-307.8(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(correlated)-303.9(with)-303(disease)-302.4(activity)-302.9(in)]TJ -7.4026 -1.3526 TD [(DMARD-naive)-308.6(patients)-299.9(with)-303(early)-300.8(RA)]TJ -47.5662 -2.7132 TD (Targonska-)Tj 0 -1.3607 TD [(Stepniak)-301.3(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.617 0 TD (22)Tj 0 0 0 1 k 1.1096 0 TD (\))Tj 1.7008 1.3607 TD [(To)-305.3(investigate)-300.7(ef)63.5(fects)-300.7(of)]TJ 0 -1.3607 TD (le)Tj /F7 1 Tf 0.6884 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(unomide)-306.1(therapy)-298.7(on)-302(SAA)]TJ -1.1258 -1.3526 TD [(concentrations)-305.9(and)-298.4(disease)-302.4(activity)]TJ 0 -1.3607 TD [(in)-304.4(RA)-296.4(patients)]TJ 17.8424 4.0739 TD [(50)-2816(RA)-304.6(\(13)-301.1(with)]TJ 3.92 -1.3607 TD [(SAA<50)-307.6(mg/L)-300(+)]TJ 0 -1.3526 TD [(37)-305.3(with)-303(SAA>)]TJ 0 -1.3607 TD (50mg/L\))Tj 8.2935 4.0739 TD 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[(li)20.7(ne)-314.1(wi)23.9(th)-312.8(th)15.4(e)-318(n)0(o)20.5(t)0(i)18.9(o)0(n)-313.7(t)0(h)21.4(a)0(t)-311.3(S)0(A)15.2(A)12.7(ca)17.5(n)-324.3(b)0(e)-313.3(r)11.9(ea)23.5(di)16.1(ly)-312.5(p)12.7(r)0(o)16.6(d)12.8(uc)17(ed)-311.2(lo)21.9(ca)17.5(ll)22.6(y)-323.8(b)0(y)]TJ ET 0 0 0 0.7 k 45.354 471.288 504.567 0.28345 re f 45.354 706.053 504.567 0.28351 re f 45.354 668.806 177.165 0.22675 re f 263.679 668.806 m 222.52 668.806 l 222.52 669.033 l 263.679 669.033 l f* 263.679 668.806 286.242 0.22675 re f BT /F1 1 Tf 6.9999 0 0 6.9999 45.3543 712.2896 Tm 0 0 0 1 k [(TABLE)-301(1)-428(|)]TJ /F6 1 Tf 5.1349 0 TD (Continued)Tj /F1 1 Tf -5.1349 -2.6079 TD [(First)-305.4(author)]TJ 0 -1.3526 TD (\(reference)Tj 0 -1.3607 TD (number\))Tj 9.6704 2.7132 TD [(The)-298.2(aim)-299.7(of)-305.1(the)-300(study)-304.3(regarding)]TJ 1.5388 -1.3526 TD [(the)-300(clinical)-305.2(utility)-305.8(of)-297(SAA)]TJ 14.7242 1.3526 TD (Number)Tj -0.6236 -1.3526 TD [(of)-297(patients)]TJ 7.2649 1.3526 TD (Diagnosis)Tj -0.2349 -1.3526 TD [(\(number)-298.7(of)]TJ 0.5183 -1.3607 TD (patients\))Tj 7.1353 2.7132 TD [(Method)-300(used)]TJ 1.2959 -1.3526 TD [(for)-300.8(SAA)]TJ -0.6803 -1.3607 TD (measuring)Tj 14.3841 2.7132 TD [(Results)-303(/)-300.1(Comments)]TJ /F6 1 Tf -54.9931 -5.1754 TD [(De)-303.3(Seny)-297.7(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.5117 0 TD (39)Tj 0 0 0 1 k 1.1015 0 TD [(\))-1575.2(T)0(o)-305.3(identify)-298(RA)-304.6(serum)-302.2(biomarkers)]TJ 1.8142 -1.3606 TD [(by)-306.4(a)-299.9(proteomic)-302.4(approach)]TJ 17.567 1.3606 TD [(103)-2539.4(RA)-304.6(\(n=34\))]TJ 4.1953 -1.3606 TD [(AS)-305.1(\(n=19\))]TJ 0 -1.3526 TD [(PsA)-303.9(\(n=22\))]TJ 0 -1.3606 TD [(OA)-304.4(\(n=20\))]TJ 0 -1.3526 TD [(HC)-306.8(\(n=16\))]TJ 8.2935 5.4264 TD [(SELDI-TOF)-298.8(MS,)]TJ 0 -1.3606 TD [(Western)-300.1(blot)]TJ /F19 1 Tf 8.0829 1.3606 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(and)-306.5(its)-300.3(truncated)-307.5(forms)-298.3(are)-304(signi)]TJ /F7 1 Tf 15.9634 0 TD ()Tj /F6 1 Tf 0.4374 0 TD (cantly)Tj -18.3202 -1.3606 TD [(elevated)-309.2(in)-296.3(sera)-302.9(from)-299.4(RA)-304.6(patients)-299.9(compared)-305.2(to)-299(healthy)]TJ 0 -1.3526 TD [(controls)-305.5(and)-298.4(patients)-308(with)-303(osteoarthritis)]TJ -47.5662 -4.0739 TD [(Li)-296.3(et)-308.6(al.)-298.4(\()]TJ 0 0 0 0.7 k 3.6122 0 TD (40)Tj 0 0 0 1 k 1.1015 0 TD [(\))-4474.7(T)0(o)-305.3(screen)-298.6(candidate)-304(RA)]TJ 4.7137 -1.3526 TD [(associated)-302(serum)-302.2(proteins)-309.8(by)]TJ 0 -1.3606 TD [(comparative)-307.8(proteomics)]TJ 17.8424 2.7132 TD [(76)-2816(RA)-304.6(\(n=38\))]TJ 3.92 -1.3526 TD [(HC)-306.8(\(n=38\))]TJ 8.2935 1.3526 TD [(2-DE,)-299.7(MS,)]TJ 0 -1.3526 TD (ELISA)Tj /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(serum)-302.2(concentration)-307(is)-299.7(signi)]TJ /F7 1 Tf 14.1168 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(higher)-302.7(in)-296.3(RA)]TJ -16.4736 -1.3526 TD [(patients)-308(compared)-305.2(to)-299(HC)]TJ -47.5662 -2.7213 TD [(Seok)-299.5(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 5.0863 0 TD (41)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3000.7(T)0(o)-305.3(identify)-298(biomarkers)-308(for)]TJ 3.2397 -1.3526 TD [(improving)-301.6(the)-304(accuracy)-304(of)-299.5(RA)]TJ 0 -1.3607 TD (prescreening)Tj 17.8424 2.7132 TD [(80)-2816(RA)-304.6(\(n=40\))]TJ 3.92 -1.3526 TD [(HC)-306.8(\(n=40\))]TJ 8.2935 1.3526 TD (LC-MS/MS,)Tj 0 -1.3526 TD (ELISA)Tj /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA4)-302.5(is)-299.7(signi)]TJ /F7 1 Tf 5.5965 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-309.2(higher)-294.7(in)-304.4(sera)-302.9(with)-303(high)]TJ -7.9534 -1.3526 TD [(rheumatoid)-310.8(factor)-296.4(values)-307.4(and)-298.4(may)-299.6(represent)-306.2(a)-299.9(novel)]TJ 0 -1.3607 TD [(prescreening)-309.3(marker)-298(for)-303.4(RA)-296.4(diagnosis)]TJ -47.5662 -1.3526 TD [(Nys)-301.7(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 4.5355 0 TD (42)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3551.4(T)0(o)-305.3(explore)-297.8(SAA)-303.7(isoforms)-297.1(in)]TJ 3.7904 -1.3607 TD [(dif)59.5(ferent)-301.2(rheumatic)-301.1(diseases)]TJ 17.567 1.3607 TD [(224)-2539.4(RA)-304.6(\(n=46:)-300.2(14)]TJ 4.1953 -1.3607 TD [(early)-300.8(onset)-301.7(+)-306(2)0(0)]TJ 0 -1.3526 TD [(low)-305.7(activity)-302.9(+)-297.9(1)0(2)]TJ 0 -1.3607 TD [(high)-306.7(activity\))]TJ T* [(AS)-305.1(\(n=30\))]TJ 0 -1.3526 TD [(SLE)-302(\(n=23\))]TJ 0 -1.3606 TD [(SSc)-305.3(\(n=20\))]TJ 0 -1.3526 TD [(OA)-304.4(\(n=43\))]TJ 0 -1.3607 TD [(HC)-306.8(\(n=62\))]TJ 8.2935 10.8609 TD (LC-MS/MS)Tj /F19 1 Tf 8.0829 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA2)-302.5(and)-298.4(SAA1)]TJ /F17 1 Tf 7.0705 0 TD (b)Tj /F6 1 Tf 0.8423 0 TD [(isoforms)-297.1(are)-304(potential)-301(RA)]TJ -9.8323 -1.3607 TD [(diagnostic)-306.1(biomarkers)-299.9(prior)-302.3(the)-304(onset)-301.7(of)-299.5(symptomatic)-307(RA)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD (SAA1)Tj /F17 1 Tf 2.4297 0 TD (a)Tj /F6 1 Tf 0.6236 0 TD 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1.5388 -1.3607 TD [(the)-300(clinical)-305.2(utility)-305.8(of)-297(SAA)]TJ 14.951 1.3607 TD (Number)Tj -0.6236 -1.3607 TD [(of)-297(patients)]TJ 6.8033 1.3607 TD (Diagnosis)Tj -0.2349 -1.3607 TD [(\(number)-298.7(of)]TJ 0.5264 -1.3526 TD (patients\))Tj 6.6656 2.7132 TD [(Method)-308.1(used)]TJ 1.304 -1.3607 TD [(for)-300.8(SAA)]TJ -0.6884 -1.3526 TD (measuring)Tj 13.9062 2.7132 TD [(Results)-303(/)-300.1(Comments)]TJ /F6 1 Tf -55.471 -5.1834 TD (Filipowicz-Sonowska)Tj 0 -1.3526 TD [(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 2.5998 0 TD (43)Tj 0 0 0 1 k 1.1015 0 TD (\))Tj 7.1596 1.3526 TD [(To)-297.2(investigate)-300.7(SAA)-303.7(levels)-297(and)-306.5(its)]TJ 0 -1.3526 TD [(correlations)-303(in)-296.3(Polish)-301.9(and)-298.4(American)]TJ 0 -1.3607 TD [(children)-300.4(with)-303(JIA)-301.1(and)-298.4(secondary)]TJ 0 -1.3526 TD (amyloidosis)Tj 18.2878 4.0658 TD [(86)-2816(JIA)-301.1(\(21)-301.1(with)]TJ 3.92 -1.3526 TD (secondary)Tj 0 -1.3607 TD (amyloidosis,)Tj 0 -1.3526 TD 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[(monitoring)-297.8(and)-306.5(predicting)-299.2(response)]TJ 0 -1.3526 TD [(to)-299(therapy)-298.7(in)-304.4(JIA)]TJ 18.2878 2.7132 TD [(23)-2816(Systemic)-307.3(JIA)-1848.1(SELDI-TOF)-306.9(MS,)]TJ 11.2902 -1.3606 TD (Immunonephelo-)Tj 0 -1.3526 TD [(metric)-301.8(assay)]TJ /F19 1 Tf 8.091 2.7132 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(is)-299.7(signi)]TJ /F7 1 Tf 5.0539 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(correlated)-303.9(with)-303(response)-299.1(to)]TJ -7.4026 -1.3606 TD [(both)-297.5(conventional)-307.2(and)-298.4(biologic)-302.8(therapy)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9114 0 TD [(Baseline)-303.4(SAA)-303.7(level)-298.1(may)-307.7(be)-294.9(used)-305.4(for)-303.4(predicting)]TJ -1.9114 -1.3607 TD [(response)-299(to)-299(therapy)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -16.83 0 TD (6)Tj ET endstream endobj 114 0 obj<> endobj 115 0 obj<> endobj 116 0 obj<> endobj 117 0 obj<> endobj 118 0 obj<> endobj 119 0 obj<> endobj 120 0 obj<> endobj 121 0 obj<> endobj 122 0 obj<> endobj 123 0 obj<> endobj 124 0 obj<> endobj 125 0 obj<> endobj 126 0 obj<> endobj 127 0 obj<> endobj 128 0 obj<> endobj 129 0 obj<> endobj 130 0 obj<> endobj 131 0 obj<> endobj 132 0 obj<> endobj 133 0 obj<> endobj 134 0 obj<> endobj 135 0 obj<> endobj 136 0 obj<> endobj 137 0 obj<> endobj 138 0 obj<> endobj 139 0 obj<> endobj 140 0 obj<> endobj 141 0 obj<> endobj 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237.6 Tm [(SAA)-301.8(IN)-302.3(RHEUMATIC)-301.1(DISEASES)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 217.644 Tm [(Th)11.1(e)-306.1(rol)15.9(e)-300.1(o)0(f)-301.1(SAA)-294.4(in)-297(pat)17.7(hog)15(ene)12.4(sis)-295(of)-295.1(rhe)16(umat)18.1(ic)-302.7(dis)16.1(ea)11.6(ses)-294.2(has)-291.2(bee)13.1(n)]TJ T* 0.0492 Tc [(most)-555.9(extensive)5.7(l)0.8(y)-555(i)-1.1(nve)5.7(s)-4.5(t)5.1(i)-1.1(gated)-552.7(i)-1.1(n)-549.6(R)0.8(A,)-550.4(a)-552.2(I)0.3(RD)-552.6(prot)5.1(otype,)]TJ T* 0 Tc [(cha)11.4(ra)13.3(cte)12.1(riz)13.6(ed)-490.3(by)-486.2(syn)14.3(ovi)12.5(al)-488.6(in)]TJ /F12 1 Tf 11.7026 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(amm)14.1(ati)14.3(on)-486.7(lea)10.9(din)14.1(g)-490.9(t)0(o)-493(a)-494(ca)11.6(rti)12.9(la)12.7(ge)]TJ -12.2277 -1.2114 TD [(de)11(stru)16.3(cti)17.2(on.)-400(Th)11.1(e)]TJ /F12 1 Tf 7.0359 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(nd)10.7(ing)-400(tha)16.8(t)-408.2(the)-392.1(SAA)-401.8(co)14.9(nce)12.4(ntr)13.5(ati)14.3(on)-403.2(mig)14.2(ht)-396.3(be)]TJ -7.561 -1.2114 TD [(eve)12.9(n)-210.9(hig)13.7(her)-204.8(in)-207.5(syn)14.3(ovi)12.5(al)]TJ /F12 1 Tf 9.2379 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(uid)-203.9(tha)16.8(n)-216.9(p)0(l)12.1(asm)13.7(a,)-210.3(led)-204.5(to)-206.5(dis)16.1(cov)13.4(ery)-200.2(of)-211.6(loc)14.2(al)]TJ -9.7631 -1.2114 TD [(SAA)-509.3(producti)-11.5(on)-504.6(by)-510(rheumatoid)-518(synovial)-509.5(cells)-512(\()]TJ 0 0 0 0.7 k 20.29 0 TD (20)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.7221 0 TD (29)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.7221 0 TD (138)Tj 0 0 0 1 k 1.4442 0 TD (\).)Tj -25.1 -1.2055 TD 0.0437 Tc [(Connolly)-542.6(e)0.2(t)-549.4(a)-2.7(l.)-549.9(demonstrated)-546.3(a)-545.7(S)-1.5(AA-induced)-546.3(leukocyte)]TJ 0 -1.2114 TD 0 Tc [(mig)14.2(rat)16.9(ion)-292.4(an)11.2(d)-297.6(t)0(i)13(ssu)12.7(e)-300.1(i)0(n)]TJ /F12 1 Tf 9.2737 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(lt)14.9(rat)10.9(io)14(n,)-297.3(an)11.2(gio)12.5(gen)18.6(esi)13.6(s)-298.4(and)-292.3(in)]TJ /F12 1 Tf 11.2669 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(amm)14.1(ati)14.3(on)]TJ -21.591 -1.2114 TD [(in)-219.5(syn)14.3(ov)15.1(ial)-216.7(cel)13.8(ls)-215.5(in)-213.5(rheu)16.8(mat)17.3(oid)-211.9(art)10.9(hr)11.8(iti)16.4(s)-226.8(\()]TJ 0 0 0 0.7 k 15.9336 0 TD (98)Tj 0 0 0 1 k 0.9489 0 TD (,)Tj 0 0 0 0.7 k 0.4416 0 TD (139)Tj 0 0 0 1 k 1.4203 0 TD [(\).)-220.8(Mo)12.4(reo)14.8(ver)14.6(,)-223.6(SAA)]TJ -18.7444 -1.2114 TD [(exh)12.6(ib)14(its)-410.8(cyt)12.3(oki)13.7(ne-)16(lik)14.3(e)-419.5(pro)11.4(pe)11(rti)12.9(es)-413.5(an)11.2(d)-422.9(can)-414.2(in)13.3(duc)11.8(e)-419.5(syn)14.3(the)13.7(sis)-408.4(and)]TJ T* [(sec)14.4(ret)13.8(ion)-244.6(of)-253.3(sev)14.6(era)11.5(l)-251.3(pro)11.4(in)]TJ /F12 1 Tf 9.9302 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(am)13.7(mat)11.3(ory)-241.5(cyt)12.3(oki)13.7(nes)14.1(,)-253.4(inc)11.5(lu)12.1(din)14.1(g)-258.1(TNF)]TJ /F17 1 Tf 14.3641 0 TD (a)Tj /F11 1 Tf 0.6147 0 TD (,)Tj -25.4401 -1.2114 TD [(IL-)12.5(6)-320.7(a)0(n)11.2(d)-327.4(IL-)18.5(1)-316.8(\()]TJ 0 0 0 0.7 k 6.6957 0 TD (140)Tj 0 0 0 1 k 1.4203 0 TD (,)Tj 0 0 0 0.7 k 0.5431 0 TD (141)Tj 0 0 0 1 k 1.4203 0 TD [(\).)-322.2(SAA)-312.3(pl)12.1(ays)-316.5(a)-320.9(pat)11.8(hog)15(eni)17.5(c)-324(rol)15.9(e)-324(i)0(n)-320.9(joi)13.4(nt)]TJ -10.0794 -1.2055 TD 0.0202 Tc [(leading)-524.4(t)-0.1(o)-524.1(t)-0.1(he)-524.6(cartilage)-524.6(d)-2.9(estruction)-524.9(by)-530.3(ac)-5.4(t)5.9(i)-0.3(v)-5.2(a)3.7(ting)-530.3(multiple)]TJ 0 -1.2114 TD 0 Tc [(rec)14.4(ep)11(tor)14.2(s,)-450.4(in)13.3(clud)17.1(ing)-441.8(N-f)11.4(orm)17(yl)-443.8(pep)11.8(tid)13.8(e)-449.3(rec)14.4(epto)19.3(r-l)13.2(ike)-440.3(1)-452(\(FP)10.7(RL)11.1(1,)]TJ 27.4512 30.262 TD [(al)12.7(so)-407.1(ca)11.6(lle)14.9(d)-411(lip)15.5(oxi)16.6(n)-413.8(A)0(4)-403.5(rec)14.4(ep)11(tor)14.2(\))-408.9(\()]TJ 0 0 0 0.7 k 13.7196 0 TD (142)Tj 0 0 0 1 k 1.4203 0 TD (,)Tj 0 0 0 0.7 k 0.6266 0 TD (143)Tj 0 0 0 1 k 1.4203 0 TD [(\),)-405.8(sca)11.5(ven)18.6(ger)-403.1(rec)14.4(ep)11(tor)]TJ -17.1868 -1.2114 TD [(cla)16.9(ss)-399.9(B)-395.7(type)-386.7(1)-404.2(\()0(S)11.3(R-B)11.3(1\))-395.4(\()]TJ 0 0 0 0.7 k 10.0495 0 TD (144)Tj 0 0 0 1 k 1.4263 0 TD (,)Tj 0 0 0 0.7 k 0.6147 0 TD (145)Tj 0 0 0 1 k 1.4263 0 TD [(\),)-393.8(Tol)15.3(l-)13.2(lik)14.3(e)-401.6(rec)14.4(ept)14.6(or)-401.1(4)-398.3(\(TL)14(R4)12.9(\))]TJ -13.5167 -1.2055 TD (\()Tj 0 0 0 0.7 k 0.3402 0 TD [(14)15.1(6)]TJ 0 0 0 1 k 1.4203 0 TD (,)Tj 0 0 0 0.7 k 0.4177 0 TD (147)Tj 0 0 0 1 k 1.4203 0 TD [(\),)-196.9(Tol)15.3(l-)13.2(lik)14.3(e)-198.7(rec)14.4(ep)11(tor)-188.7(2)-201.3(\(TL)14(R2)12.9(\))-200.1(\()]TJ 0 0 0 0.7 k 11.8756 0 TD (148)Tj /F13 1 Tf 0 0 0 1 k 1.4203 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5073 0 TD (151)Tj 0 0 0 1 k 1.4203 0 TD [(\))-200.1(a)0(n)11.2(d)-202.1(rec)14.4(ep)11(tor)14.2(s)-197(o)0(f)]TJ -18.822 -1.2114 TD 0.0184 Tc [(advanced)-523.8(glycation)-520.7(e)-1.2(nd)-523.8(products)-518.7(\(RAGE\))-521.8(\()]TJ 0 0 0 0.7 k 19.1979 0 TD 0.0223 Tc [(14)6(7)]TJ 0 0 0 1 k 1.4919 0 TD 0 Tc (,)Tj 0 0 0 0.7 k 0.7579 0 TD 0.0223 Tc [(15)6(2)]TJ 0 0 0 1 k 1.4919 0 TD 0.0197 Tc [(\).)-520.2(The)]TJ -22.9397 -1.2114 TD 0 Tc [(exp)13.5(res)16.1(sio)14(n)-360.1(o)0(f)-354.8(the)19.7(se)-353.9(rece)18.6(ptor)15(s)-358.1(i)0(s)-354.7(i)0(n)13.3(cre)14.4(ase)11.5(d)-357.2(i)0(n)-356.7(R)0(A)-352(syn)14.3(ovi)12.5(al)-351.4(ti)13(ssu)12.7(e)]TJ T* [(and)-513.1(medi)-9.1(ates)-510(SA)-8.7(A-induce)-15.8(d)-506.4(proi)-9.1(n)]TJ /F12 1 Tf 14.1732 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(amma)-8.4(tory)-512.4(and)-513.1(angioge)-9.3(nic)]TJ -14.7043 -1.2114 TD [(ef)74.4(fec)13(ts)-288.8(by)-295.2(th)15.4(e)-300.1(a)0(c)11.6(tiv)17.4(ati)14.3(on)-289.8(of)-295.1(MA)14.4(PKs)-287.8(an)11.2(d)-297.6(NF-)]TJ /F17 1 Tf 17.5509 0 TD (k)Tj /F11 1 Tf 0.5371 0 TD 0.2942 Tc (B\()Tj 0 0 0 0.7 k 1.2174 0 TD 0 Tc (153)Tj 0 0 0 1 k 1.4203 0 TD [(\).)-292.4(Mo)12.4(reo)14.9(ver)14.6(,)]TJ -20.7257 -1.2114 TD [(SA)-8.7(A)-506.5(s)0(t)-8.4(i)0(m)-8.1(ula)-10.4(tes)-517.3(the)-517.4(prod)-11.6(uct)-9.2(io)-9.8(n)-509.3(o)0(f)-515.9(matr)-12.6(ix)-513.3(me)-7.3(ta)-7(llo)-8.5(prot)-8.8(e)-7.7(ina)-9.2(se)-7.7(s)]TJ 0 -1.2055 TD [(\(MM)12.4(Ps\))-491.5(by)-492.1(chon)12.7(dro)11.4(cyt)12.3(es)-497.1(and)-489.2(syno)13(vial)]TJ /F12 1 Tf 16.8288 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(brob)14(las)12.6(ts)-497.7(\()]TJ 0 0 0 0.7 k 4.3922 0 TD (154)Tj /F13 1 Tf 0 0 0 1 k 1.4203 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5072 0 TD (156)Tj 0 0 0 1 k 1.4263 0 TD (\).)Tj -25.1 -1.2114 TD [(St)12.1(imu)10.6(la)12.7(tio)11.7(n)-360.1(o)0(f)-354.8(the)13.7(se)-353.9(car)11.5(ti)13(lag)11.1(e-)12.1(degr)15.4(adi)17.5(ng)-355.7(pro)11.4(tei)17.2(nas)11.2(es)-353.9(con)12.8(tri)13(bu)11.5(tes)]TJ T* [(to)-224.4(the)-219(chro)14.7(ni)13.3(c)-234.5(t)0(i)13(ssu)12.7(e)-234.5(i)0(n)13.3(jur)12.1(y)-228.3(i)0(n)-231.4(a)0(r)13.3(thr)15.4(itis)16.3(.)-229.6(Mat)12.7(rix)-220.9(met)14.2(al)12.6(lopr)16.8(ote)18.5(inas)14.6(e-)]TJ T* [(3)-410.2(\(MM)12.4(P-3)16.5(\))-414.9(i)0(s)-408.4(fou)16(nd)-413(hig)13.7(hly)-402.1(con)18.8(cen)12.4(tra)10.9(te)13.8(d)-416.9(i)0(n)-404.5(the)-404(syn)14.3(ovi)12.5(al)]TJ /F12 1 Tf 23.8408 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (uid)Tj -24.3719 -1.2114 TD [(as)-505.9(well)-507.6(as)-511.9(in)-505.9(the)-511.5(serum)-507.8(of)-510(RA)-507.2(patients)-516.2(and)-507.1(correlates)-515.5(with)]TJ T* [(pro)17.4(gres)14.6(sio)14(n)-401.9(o)0(f)-396.6(ero)14.9(sio)14(n)-401.9(i)0(n)-392.5(R)0(A)-399.8(\()]TJ 0 0 0 0.7 k 12.7469 0 TD (21)Tj 0 0 0 1 k 0.9429 0 TD (,)Tj 0 0 0 0.7 k 0.6206 0 TD (157)Tj 0 0 0 1 k 1.4263 0 TD [(\).)-393.8(MMP)16.5(-3)-396.3(pro)11.4(duc)11.8(ti)13(on)-397.2(is)]TJ -15.7367 -1.2055 TD [(sim)15.7(ult)15.7(aneo)20.1(usl)12.1(y)-407.3(up-)15.5(reg)14.6(ula)13.5(ted)-397.1(by)-402.6(the)-392.1(pro)11.4(in)]TJ /F12 1 Tf 16.9302 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(am)13.7(mat)11.3(ory)-396.7(cyt)18.3(oki)13.7(nes)]TJ -17.4614 -1.2114 TD [(IL-)12.5(1)]TJ /F17 1 Tf 1.6769 0 TD (b)Tj /F11 1 Tf 0.5371 0 TD [(,)-193.8(TNF)]TJ /F17 1 Tf 2.2737 0 TD (a)Tj /F11 1 Tf 0.8176 0 TD [(an)11.2(d)-196.1(IL-)12.5(17.)-184.6(Cyt)13.6(oki)13.7(ne)14.1(-)-195(and)-190.9(SAA)15.9(-dr)14.6(ive)12.1(n)-193(pro)11.4(du)13.6(cti)11.2(on)-188.3(of)]TJ -5.3052 -1.2114 TD [(MMP)16.5(-3)-283(in)-279.1(the)-272.8(rheu)16.8(mat)11.3(oi)14(d)-285.6(joi)13.4(nt)-278.9(app)14.9(ear)11.5(s)-286.5(t)0(o)-278.1(b)0(e)-277.5(a)-285.1(key)-278.1(med)11.4(iat)14.3(or)-275.8(of)]TJ T* [(the)-278.7(car)11.5(til)12.3(ag)11.8(e)-294.2(d)0(e)11(str)15.5(uc)11(tio)11.7(n.)-285.3(Fur)13.5(the)13.7(rm)12.3(ore)14.9(,)-295.2(SAA)-282.5(ind)14.1(uc)11(es)-288.2(pe)11(ntr)13.5(axi)13.2(n)-294.5(3)]TJ T* [(\(PT)15.1(X3\))-239.8(in)-249.3(rh)11.8(eum)11.4(ato)15.6(id)-246.4(syn)14.3(ovi)12.5(oc)14.9(yte)12.3(s.)-247.5(PT)12.3(X3)-248.6(is)-247.3(al)12.7(so)-246(an)-245.4(ac)11.6(ute-)16.5(pha)14(se)]TJ T* [(rea)11.5(ct)13.8(ant)-277.6(inv)11.8(olv)20.4(ed)-287.4(in)-279.1(amp)14.5(li)]TJ /F12 1 Tf 10.4613 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(ca)11.6(tio)11.7(n)-288.5(o)0(f)-277.2(the)-278.7(in)]TJ /F12 1 Tf 6.1109 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(am)13.7(mat)11.3(ory)-277.3(res)16.1(po)11.5(nse)14.1(.)]TJ -17.6225 -1.2114 TD [(Th)11.1(is)-366.6(loo)14.7(p)-369.2(see)14.4(ms)-363.7(to)-367.7(in)13.3(vol)14.5(ve)-367.3(N-)12.8(for)15.2(myl)-359.8(pep)11.8(tid)13.8(e)-371.7(rec)14.4(ep)11(tor)-361.7(lig)13.2(an)11.2(d-1)]TJ 9.5 0 0 9.5 306.1417 114.1795 Tm [(\(FR)14.9(LP-)14.8(1\))-294(\()]TJ 0 0 0 0.7 k 4.3445 0 TD (158)Tj 0 0 0 1 k 1.4263 0 TD (\).)Tj -4.5056 -1.2114 TD [(A)-375.2(new)-383.1(subset)-380.6(of)-378.7(interleukin)-385.3(17)-378.8(\(IL-17\))-378.5(producing)-388.7(T)-376.6(helper)]TJ -1.2651 -1.2114 TD [(cells)-231.6(\(Th17)-233.5(cells\))-234.7(has)-231.5(been)-233.6(recently)-238.6(reported)-232.3(to)-236.4(play)-232.7(a)-231.4(critical)-231.1(role)]TJ T* [(in)-380.6(in)]TJ /F12 1 Tf 1.9813 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-383.6(joint)-378.9(diseases)-379.9(including)-387.5(RA,)-378.7(AS)-378.7(and)-381.8(psoriatic)]TJ -2.5124 -1.2114 TD [(arthritis)-265.3(\(PsA\))-267.1(\()]TJ 0 0 0 0.7 k 6.3615 0 TD (159)Tj /F13 1 Tf 0 0 0 1 k 1.4382 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5073 0 TD (165)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-262.5(In)-265.8(contrast)-265.1(to)-266.2(the)-260.8(other)-268.1(ef)62.5(fector)-265.2(T-cell)]TJ ET 0 0 0 0.7 k 45.354 706.053 504.567 0.28345 re f 45.354 386.646 504.567 0.28345 re f 45.354 669.656 504.567 0.22681 re f BT /F1 1 Tf 6.9999 0 0 6.9999 45.3543 712.2896 Tm 0 0 0 1 k [(TABLE)-301(3)-428(|)]TJ /F6 1 Tf 5.1349 0 TD [(Characteristics)-305(and)-306.5(results)-298.7(of)-299.5(articles)-306.1(investigating)-303.9(clinical)-300.6(utility)-303.5(of)-299.5(SAA)-295.6(in)-304.4(patients)-299.9(with)-303(ankylosing)-303.5(spondylitis.)]TJ /F1 1 Tf -5.1349 -2.4864 TD [(First)-305.4(author)]TJ 0 -1.3526 TD [(\(reference)-309(number\))]TJ 11.2335 1.3526 TD [(The)-306.3(aim)-299.7(of)-297(the)-308.1(study)-296.2(regarding)]TJ 1.5388 -1.3526 TD [(the)-308.1(clinical)-297.1(utility)-305.8(of)-297(SAA)]TJ 14.8619 1.3526 TD (Number)Tj -0.6236 -1.3526 TD [(of)-305.1(patients)]TJ 7.0382 1.3526 TD (Diagnosis)Tj -0.2349 -1.3526 TD [(\(number)-298.7(of)]TJ 0.5183 -1.3607 TD (patients\))Tj 6.9005 2.7132 TD [(Method)-308.1(used)]TJ 1.2959 -1.3526 TD [(for)-300.8(SAA)]TJ -0.6803 -1.3607 TD (measuring)Tj 13.7685 2.7132 TD [(Results)-303(/)-300.1(Comments)]TJ /F6 1 Tf -55.6167 -5.1753 TD [(Lange)-297.9(et)-308.6(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.5317 0 TD (49)Tj 0 0 0 1 k 1.1096 0 TD [(\))-3980.6(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(as)-298.8(marker)-298(of)]TJ 4.2196 -1.3607 TD (in)Tj /F7 1 Tf 0.7046 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammation)-304.4(in)-296.3(AS)]TJ 16.9677 1.3607 TD [(72)-2824.1(AS)-6573.8(ELISA)]TJ /F19 1 Tf 19.8429 0 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(correlates)-299.7(signi)]TJ /F7 1 Tf 8.5608 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(with)-303(disease)-302.4(activity)-302.9(in)]TJ -10.9095 -1.3607 TD [(AS)-297(patients)-299.9(\(assessed)-302.9(by)-306.4(BASDAI)-297.8(score\),)-302.9(but)-306.9(is)-299.7(not)]TJ 0 -1.3525 TD [(superior)-296.9(to)-307.1(CRP)-296(or)-302.3(ESR)]TJ -48.8135 -1.3607 TD [(Jung)-299.6(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 5.0134 0 TD (50)Tj 0 0 0 1 k 1.1015 0 TD [(\))-4507.1(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(as)-298.8(marker)-298(of)]TJ 4.7461 -1.3526 TD [(disease)-302.4(activity)-302.9(in)-296.3(AS)-297(patients)]TJ 18.1097 1.3526 TD [(76)-2824.1(AS)-297(\(n=38\))]TJ 3.9281 -1.3526 TD [(HC)-298.7(\(n=38\))]TJ 7.8238 1.3526 TD (Immunonephelo-)Tj 0 -1.3526 TD [(metric)-301.9(assay)]TJ /F19 1 Tf 8.091 1.3526 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(is)-299.7(a)-299.9(more)-298.6(sensitive)-308.1(marker)-298(than)-299.5(ESR)-304.7(and)]TJ -1.9114 -1.3526 TD [(CRP)-296(in)-304.4(assessing)-299.1(disease)-302.4(activity)-302.9(in)-304.4(AS)-297(\(evaluated)-308.6(by)]TJ 0 -1.3606 TD [(BASDAI)-297.8(score\))]TJ -48.8135 -1.3526 TD [(De)-303.3(Vries)-295.9(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.4469 0 TD (51)Tj 0 0 0 1 k 1.1096 0 TD [(\))-3065.4(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(as)-298.8(disease)-302.4(activity)]TJ 3.3044 -1.3607 TD [(marker)-298(in)-304.4(AS)-297(patients)-299.9(receiving)]TJ T* [(anti-TNF)-299.5(therapy)]TJ 17.8343 2.7213 TD [(155)-2547.5(AS)-6573.8(ELISA)]TJ /F19 1 Tf 20.1182 0 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(correlates)-299.7(signi)]TJ /F7 1 Tf 8.5608 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(with)-303(disease)-302.4(activity,)]TJ -10.9095 -1.3607 TD [(response)-299(to)-299(anti-TNF)-307.6(therapy,)-304.1(and)-298.4(has)-302.3(high)-298.6(predictive)]TJ T* [(value)-300.5(for)-295.3(response)-307.1(to)-299(anti-TNF)-307.6(therapy)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(may)-299.6(be)-303(indicator)-304.3(of)-299.5(anti-drug)-298.8(antibodies)]TJ -1.9114 -1.3606 TD (development)Tj -48.8135 -1.3526 TD [(Li)-296.3(et)-308.6(al.)-298.4(\()]TJ 0 0 0 0.7 k 3.6122 0 TD (52)Tj 0 0 0 1 k 1.1015 0 TD 5.9082 Tc [(\)T)5908.2(o)]TJ /F7 1 Tf 7.5484 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(a)-299.9(diagnostic)-306.1(marker)-306.1(for)-295.3(AS)]TJ -1.8385 -1.3607 TD [(by)-298.3(proteomic)-302.4(approach)]TJ 18.1097 1.3607 TD [(76)-2824.1(AS)-297(\(n=38\))]TJ 3.9281 -1.3607 TD [(HC)-298.7(\(n=38\))]TJ 7.8238 1.3607 TD (2-DE+MALDI-)Tj 0 -1.3607 TD [(TOF)-300(MS,)]TJ 0 -1.3526 TD (ELISA)Tj /F19 1 Tf 8.091 2.7132 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(may)-299.6(be)-303(used)-297.3(as)-306.9(a)-299.9(diagnostic)-298(indicator)-304.3(of)-299.5(AS)]TJ -1.9114 -1.3607 TD [(,)-296.9(since)-303.8(it)-301.4(is)-299.7(over-expressed)-305.9(by)-298.3(more)-306.7(than)-299.5(3-fold)-303(in)-296.3(the)]TJ 0 -1.3526 TD [(sera)-294.8(of)-299.5(AS)-305.1(patients)-299.9(compared)-305.2(to)-299(healthy)-304.6(controls)]TJ -48.8135 -1.3607 TD [(Rademacher)-305.6(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 8.3583 0 TD (53)Tj 0 0 0 1 k 1.1015 0 TD 1.1622 Tc [(\)T)1162.2(o)]TJ /F7 1 Tf 2.8023 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(biomarkers)-308(for)-303.4(predicting)]TJ -1.8385 -1.3607 TD [(radiographic)-301.5(progression)-301.4(of)-299.5(AS)]TJ 17.8343 1.3607 TD [(117)-2547.5(AS)-297(\(28)]TJ 4.2034 -1.3607 TD [(progressors)-299.4(+)]TJ 0 -1.3526 TD (89)Tj 0 -1.3607 TD (nonprogressors\))Tj 7.8238 4.0739 TD (ELISA)Tj /F19 1 Tf 8.091 0 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(levels)-297(are)-304.1(signi)]TJ /F7 1 Tf 8.3421 0 TD 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[(\))-4920.1(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(as)-298.8(a)-299.9(marker)-306.1(of)]TJ 5.1591 -1.3526 TD [(disease)-302.4(activity)-302.9(and)-298.4(treatment)]TJ 0 -1.3606 TD [(response)-299(in)-304.4(TA)]TJ 17.7857 2.7132 TD [(TA)-305.2(\(n=99:)-300.2(43)-297.2(active)-305.9(+)]TJ 0 -1.3526 TD [(48)-305.3(inactive)-302.5(+)-297.9(8)]TJ 0 -1.3606 TD (indeterminate\),)Tj 0 -1.3526 TD [(HC)-306.8(\(n=40\))]TJ 10.2535 4.0658 TD (ELISA)Tj /F19 1 Tf 7.1677 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(is)-299.7(a)-299.9(more)-298.6(sensitive)-300(biomarker)-309.1(of)-299.5(disease)-302.4(activity)]TJ -1.9195 -1.3526 TD [(and)-306.5(treatment)-305.6(response)-299(than)-299.5(CRP)-304.1(or)-302.3(ESR)-296.6(in)-304.4(TA)-297.1(patients)]TJ -46.0679 -4.0739 TD [(Hocevar)-306.3(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.455 0 TD (58)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3065.4(T)0(o)-297.2(explore)-305.9(serum)-302.2(biomarkers)-299.9(utility)-303.5(for)]TJ 3.3044 -1.3607 TD [(predicting)-299.2(relapse)-307.4(in)-296.3(GCA)-304(patients)]TJ 0 -1.3526 TD [(receiving)-296.5(GCs)]TJ 17.7857 2.7132 TD (GCA)Tj 0 -1.3607 TD [(\(n=68:)-308.3(31)-297.2(relapsed)-302.4(+)]TJ 0 -1.3526 TD [(37)-305.3(nonrelapsed\))]TJ 10.2535 2.7132 TD (ND)Tj /F19 1 Tf 7.1677 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(High)-302.7(baseline)-300.2(SAA)-303.7(values)-299.4(are)-304(predictors)-305.3(of)-299.5(early)-300.8(relapse)]TJ -1.9195 -1.3607 TD [(in)-304.4(GCA)-304(patients)-299.9(treated)-300.4(with)-303(GCs)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(Baseline)-303.4(SAA)-295.6(is)-307.8(better)-300.2(correlated)-303.9(with)-303(future)-304.5(relapses)]TJ -1.9195 -1.3606 TD [(than)-307.6(CRP)-296(or)-302.3(ESR)]TJ -46.0679 -1.3526 TD [(Burja)-298.6(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 5.0944 0 TD (59)Tj 0 0 0 1 k 1.1096 0 TD [(\))-4418(T)0(o)-297.2(identify)-306.1(serum)-302.2(biomarkers)-299.9(for)]TJ 4.657 -1.3607 TD [(monitoring)-297.8(disease)-302.4(activity)-302.9(in)-304.4(patients)]TJ 0 -1.3526 TD [(with)-294.9(GCA)]TJ 17.7857 2.7132 TD [(GCA)-304(\(n=82:)-300.3(35)]TJ 0 -1.3607 TD [(relapsed)-302.4(+)-306(4)0(7)]TJ 0 -1.3526 TD (nonrelapsed\),)Tj 0 -1.3607 TD [(HC)-306.8(\(n=46\))]TJ 10.2535 4.0739 TD (Immuno-)Tj 0 -1.3607 TD (nephelometric)Tj 0 -1.3526 TD (assay)Tj /F19 1 Tf 7.1677 2.7132 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(may)-299.6(be)-303(used)-297.3(as)-298.8(a)-299.9(marker)-306.1(for)-303.4(GCA)-295.9(diagnosis)-304.1(and)]TJ -1.9195 -1.3607 TD [(disease)-302.4(activity)-302.9(\(more)-302.6(sensitive)-308.1(than)-299.5(CRP)-304.1(or)-294.2(ESR\))]TJ -46.0679 -4.0739 TD [(Dartavel)-305(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.3497 0 TD (60)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3170.7(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(as)-298.8(a)-299.9(marker)-306.1(of)]TJ 3.4097 -1.3526 TD [(disease)-302.4(activity)-302.9(in)-296.3(GCA)]TJ 17.7857 1.3526 TD [(GCA)-304(\(n=80:)-300.3(21)-305.3(active)]TJ 0 -1.3526 TD [(+)-306(5)0(9)-297.2(inactive\),)]TJ 0 -1.3607 TD [(microbial)-305.5(infections)]TJ 0 -1.3525 TD (\(n=8\))Tj 10.2535 4.0658 TD (ND)Tj /F19 1 Tf 7.1677 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(is)-299.7(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(dif)59.5(ferent)-301.2(between)-305.7(GCA)-304(patients)-299.9(with)]TJ -7.4026 -1.3526 TD [(active)-305.9(and)-298.4(inactive)-302.5(disease)]TJ /F19 1 Tf 0 -1.3607 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(levels)-297(are)-304.1(not)-302.6(dif)67.6(ferent)-301.2(between)-305.7(patients)-308(with)-303(active)]TJ -1.9195 -1.3525 TD [(GCA)-304(and)-298.4(microbial)-305.5(infections)]TJ -46.0679 -1.3607 TD [(Van)-303.6(Sleen)-295.5(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 7.1758 0 TD (61)Tj 0 0 0 1 k 1.1096 0 TD 2.3365 Tc [(\)T)2336.5(o)]TJ /F7 1 Tf 3.9767 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(biomarkers)-308(for)-303.4(predicting)]TJ -1.8385 -1.3526 TD [(disease)-302.4(course)-297.1(in)-304.4(GCA)-295.9(and)-306.5(for)]TJ 0 -1.3606 TD [(monitoring)-297.8(response)-307.1(too)-297.7(therapy)]TJ 17.7857 2.7132 TD [(GCA)-304(\(n=41\))]TJ 0 -1.3526 TD [(HC)-306.8(\(n=33\))]TJ 0 -1.3606 TD [(microbial)-305.5(infections)]TJ T* (\(n=13\))Tj 10.2535 4.0739 TD (ELISA)Tj /F19 1 Tf 6.9999 0 0 6.9999 367.8235 478.1479 Tm ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(is)-299.7(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(elevated)-309.2(in)-296.3(GCA)-304(compared)-305.2(to)-299(HCs,)]TJ -7.4026 -1.3526 TD [(but)-306.8(not)-302.6(compared)-297.1(to)-307.1(patients)-299.9(with)-303(infection)]TJ /F19 1 Tf 0 -1.3606 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(correlates)-299.7(with)-303(disease)-302.4(activity)-302.9(in)-296.3(GCA)-304(patients)]TJ -1.9195 -1.3607 TD [(receiving)-304.6(GCs)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(Baseline)-303.4(SAA)-295.6(levels)-305.1(do)-301.5(not)-302.6(have)-299.3(a)-299.9(predictive)-308.9(value)-300.5(for)]TJ -1.9195 -1.3607 TD [(disease)-302.4(course)-305.2(in)-296.3(GCA)]TJ -46.0679 -1.3526 TD [(Mitani)-302.5(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.4102 0 TD (62)Tj 0 0 0 1 k 1.1015 0 TD 4.1102 Tc [(\)T)4110.2(o)]TJ /F7 1 Tf 5.7504 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(potential)-309.1(biomarkers)-299.9(of)]TJ -1.8385 -1.3607 TD [(coronary)-296.5(artery)-304.1(lesions)-302.3(late)-301.9(after)-305.7(KD)]TJ 17.7857 1.3607 TD [(KD)-305.9(\(n=65:)-300.3(20)-297.2(with)]TJ 0 -1.3607 TD [(coronary)-304.6(artery)]TJ 0 -1.3526 TD [(lesions,)-307.7(45)-297.2(without\))]TJ 10.2535 2.7132 TD (Immuno-)Tj 0 -1.3607 TD (nephelometric)Tj 0 -1.3526 TD (assay)Tj /F19 1 Tf 7.1677 2.7132 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(is)-299.7(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(higher)-302.8(in)-304.4(patients)-299.9(with)-303(coronary)]TJ -7.4026 -1.3607 TD [(artery)-304.1(lesion)-303.5(persistence)-302.6(late)-301.9(after)-305.7(KD)-297.9(than)-299.5(in)-304.4(patients)-299.9(with)]TJ 0 -1.3526 TD [(regressed)-307.7(or)-302.3(without)-297.8(lesions)]TJ -46.0679 -1.3607 TD [(Whitin)-302.7(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.5155 0 TD (63)Tj 0 0 0 1 k 1.1015 0 TD 4.0049 Tc [(\)T)4004.9(o)]TJ /F7 1 Tf 5.6451 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(a)-299.9(serum)-302.2(biomarker)-309.1(for)]TJ -1.8385 -1.3607 TD [(diagnosis)-296(of)-299.5(KD)]TJ 17.7857 1.3607 TD [(KD)-305.9(\(n=68\))]TJ 0 -1.3607 TD [(Febrile)-304.9(controls)]TJ 0 -1.3526 TD (\(n=61\))Tj 10.2535 2.7132 TD (SELDI-TOF)Tj 0 -1.3607 TD (MS)Tj 0 -1.3526 TD [(+)-306(hybrid)-301.8(MS)]TJ 0 -1.3607 TD (immunoassay)Tj /F19 1 Tf 7.1677 4.0739 TD ()Tj /F6 1 Tf 1.9195 0 TD [(A)-298.3(truncated)-307.5(form)-299.4(of)-299.5(SAA)-303.7(\(7860)-298.7(Da\))-299.1(may)-307.7(be)-294.9(a)-299.9(diagnostic)]TJ -1.9195 -1.3607 TD [(marker)-306.1(for)-303.4(KD)]TJ -46.0679 -4.0658 TD [(Purevdorj)-300.3(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.9491 0 TD (64)Tj 0 0 0 1 k 1.1096 0 TD 2.5633 Tc [(\)T)2563.3(o)]TJ /F7 1 Tf 4.2034 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(a)-299.9(serum)-302.2(biomarker)-309.1(for)]TJ -1.8385 -1.3607 TD [(diagnosis)-296(of)-299.5(HSP)]TJ 17.7857 1.3607 TD [(HSP)-304.6(\(n=127\),)]TJ 0 -1.3607 TD [(Infections)-308.4(\(n=110\),)]TJ 0 -1.3526 TD [(HC)-306.8(\(n=121\))]TJ 10.2535 2.7132 TD (ELISA)Tj /F19 1 Tf 7.1677 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-303.7(is)-299.7(a)-299.9(sensitive)-300(and)-298.4(speci)]TJ /F7 1 Tf 12.0191 0 TD ()Tj /F6 1 Tf 0.4373 0 TD [(c)-299.9(diagnostic)-306.1(biomarker)-301(for)]TJ -14.376 -1.3607 TD [(HSP)-304.6(\(better)-304.1(than)-299.5(CRP\))]TJ -46.0679 -2.7132 TD [(Kuret)-302.8(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.1915 0 TD (65)Tj 0 0 0 1 k 1.1015 0 TD [(\))-4328.9(T)0(o)-297.2(evaluate)-301.6(serum)-302.2(biomarkers)-308(for)]TJ 4.5679 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6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -16.83 0 TD (8)Tj ET endstream endobj 186 0 obj<> endobj 187 0 obj<> endobj 188 0 obj<> endobj 189 0 obj<> endobj 190 0 obj<> endobj 191 0 obj<> endobj 192 0 obj<> endobj 193 0 obj<> endobj 194 0 obj<> endobj 195 0 obj<> endobj 196 0 obj<> endobj 197 0 obj<> endobj 198 0 obj<> endobj 199 0 obj<> endobj 200 0 obj<> endobj 201 0 obj<> endobj 202 0 obj<> endobj 203 0 obj<> endobj 204 0 obj<> endobj 205 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 206 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 207 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 208 0 obj<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 209 0 obj<>stream /GS1 gs BT /F11 1 Tf 9.5 0 0 9.5 45.3543 158.9669 Tm 0 0 0 1 k 0 Tc 0 Tw [(targeted)-431.3(IL-1)]TJ /F17 1 Tf 5.347 0 TD (b)Tj /F11 1 Tf 0.9668 0 TD [(blockade)-428.6(is)-432.3(the)-427.9(mainstay)-429.1(of)-432.4(treatment,)-431.4(and)-429.6(its)]TJ -6.3138 -1.2055 TD [(remarkable)-295.1(ef)]TJ /F12 1 Tf 5.4902 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cacy)-290.1(is)-295(well)-292.8(established.)-291.6(Biological)-293.2(therapies)-298.8(such)]TJ -6.0214 -1.2114 TD 0.0373 Tc [(as)-535.6(anakinra)-534.2(\(recombi)4.9(n)-0.6(an)5.4(t)-537.9(I)0.3(L-1)-540(r)1.5(ecepto)6.2(r)-535.6(a)-3.1(nt)5.1(agon)5.4(ist\))-532.8(and)]TJ T* 0.0314 Tc [(canakinumab)-530.8(\()4.4(monoclonal)-536.2(anti-IL-1)]TJ /F17 1 Tf 16.1127 0 TD 0 Tc (b)Tj /F11 1 Tf 1.104 0 TD 0.0313 Tc [(antibody\))-532.8(are)-531.4(both)]TJ -17.2167 -1.2114 TD 0 Tc [(licensed)-302.1(for)-301.1(several)-308.7(autoin)]TJ /F12 1 Tf 10.515 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-300.1(diseases.)]TJ -9.781 -1.2114 TD [(I)-7.2(n)-509.3(19)-14.7(74)-8.8(,)-516(H)0(u)-9(s)0(b)-13.2(y)-514.7(e)-7.7(t)-509.6(al)-11.2(.)-516(i)0(d)-7.7(e)-7.7(n)-8(t)-8.3(i)]TJ /F12 1 Tf 12.2039 0 TD ()Tj /F11 1 Tf 0.5371 0 TD 0.0087 Tc [(ed)-503.7(am)8.7(yloid)-503.7(p)8.7(rote)8.7(in)-506.6(A)-503.8(a)8.7(s)-509.2(a)]TJ -14.0061 -1.2114 TD 0.5338 Tc [(p)516.7(r)515.9(o)520.6(t)513.5(e)520.1(o)514.6(l)521.2(y)514.4(t)519.5(i)519.3(cd)516.7(e)514.2(r)515.9(i)519.3(v)520.4(a)517.3(t)513.5(eo)520.6(fS)518.4(A)516.6(A)-2.6(b)520.6(y)1.2(as)521.8(e)514.2(q)518.6(u)516.7(e)514.2(n)519.8(c)514.2(ea)517.3(n)519.8(a)517.3(l)515.3(y)520.4(s)515.9(i)519.3(so)520.6(ft)519.5(h)515.8(e)]TJ 0 -1.2055 TD 0 Tc [(protein)-313.6(puri)]TJ /F12 1 Tf 4.8815 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ed)-317.2(from)-312.7(amyloid)-307.8(deposits.)-319.5(Amyloid)-314.4(protein)-313.6(A)-309.6(i)0(s)-312.9(a)]TJ -5.4127 -1.2114 TD [(76)-289.2(amino)-290.6(acids)-288.6(N-terminal)-293.2(derivate)-288.3(of)-289.1(SAA)-288.5(\()]TJ 0 0 0 0.7 k 18.1596 0 TD (171)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-286.4(The)-289(aberrant)]TJ 7.8534 9.6795 TD 0.057 Tc [(pro)-4(c)1.6(e)-4.4(s)3.3(sing)-559.2(of)-559.1(SAA)-556.9(i)0.7(n)-559.7(m)-2.3(acrophag)-4.2(e)-553.4(l)-3.3(ysosomes)-557.7(l)-3.3(e)1.6(ads)-557.7(t)0.9(o)]TJ 0 -1.2055 TD 0.0482 Tc [(accumulation)-544.7(of)-550(n)4.4(e)-1.3(wly)-550.1(f)5(ormed)-547.8(A)1.2(A)-547.8(a)1.8(mylo)5.1(id)]TJ /F12 1 Tf 20.9644 0 TD 0 Tc ()Tj /F11 1 Tf 0.5789 0 TD 0.0482 Tc [(brils)-548.6(a)1.8(nd)]TJ -21.5432 -1.2114 TD 0 Tc [(development)-381(of)-378.7(AA)-380.5(amyloidosis)-377.4(\()]TJ 0 0 0 0.7 k 13.9046 0 TD (172)Tj 0 0 0 1 k 1.4382 0 TD (,)Tj 0 0 0 0.7 k 0.5908 0 TD (173)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-381.9(The)-378.5(generation)-378(of)]TJ -17.3718 -1.2114 TD [(SAA)-413.8(N-terminal)-412.5(fragments)-413.2(has)-410.6(been)-412.6(related)-416.1(to)-409.4(the)-410(activity)-413.1(of)]TJ T* [(MMPs)-281.9(\()]TJ 0 0 0 0.7 k 3.318 0 TD (174)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-280.4(MMP1)-280.3(has)-279.3(a)-279.1(putative)-282.1(cleavage)-280.7(site)-281.2(next)-278.1(to)-278.2(the)-278.7(site)]TJ -4.7562 -1.2114 TD [(of)-313(SAA1)-316.7(amino)-314.5(acid)-318.4(substitutions)-319.7(at)-317.3(positions)-315.7(52)-313.1(and)-316.2(57)-313.1(\()]TJ 0 0 0 0.7 k 23.6618 0 TD (175)Tj 0 0 0 1 k 1.4382 0 TD (\).)Tj -25.1 -1.2114 TD (SAA1)Tj /F17 1 Tf 2.3214 0 TD (a)Tj /F11 1 Tf 0.9011 0 TD [(has)-273.3(a)-273.2(higher)-274.7(af)]TJ /F12 1 Tf 5.8125 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(nity)-277(for)-271.3(cleavage)-274.7(by)-277.3(MMP1)-274.3(than)-271.7(SAA1)]TJ /F17 1 Tf 15.5517 0 TD (b)Tj /F11 1 Tf -25.1179 -1.2055 TD 0.0434 Tc [(or)-541.5(SAA1)]TJ /F17 1 Tf 3.9804 0 TD 0 Tc (g)Tj /F11 1 Tf 0.9906 0 TD 0.0432 Tc [(con)5.3(s)-4.6(e)5.7(q)-1.8(uentl)6.8(y)-543.1(leadi)4.8(n)-0.6(g)-543.1(t)]TJ 10.3479 0 TD 0.5849 Tc [(oal)542.5(a)544.5(r)543.1(g)541.6(e)541.4(r)0(a)544.5(m)537.6(o)547.8(u)538(n)541.1(t)546.7(so)541.8(f)]TJ -15.319 -1.2114 TD 0 Tc [(amyloidogenic)-330.7(truncated)-329.5(SAA)-330.2(forms)-330.6(\()]TJ 0 0 0 0.7 k 15.4861 0 TD (175)Tj 0 0 0 1 k 1.4322 0 TD [(\).)-328.2(These)-332.5(data)-327(indicate)]TJ ET 0 0 0 0.7 k 45.354 706.053 504.567 0.28345 re f 45.354 405.638 504.567 0.28348 re f 45.354 669.656 504.567 0.22681 re f BT /F1 1 Tf 6.9999 0 0 6.9999 45.3543 712.2896 Tm 0 0 0 1 k [(TABLE)-301(5)-428(|)]TJ /F6 1 Tf 5.1349 0 TD [(Characteristics)-305(and)-306.5(results)-298.7(of)-299.5(articles)-306.1(investigating)-303.9(clinical)-300.6(utility)-303.5(of)-299.5(SAA)-295.6(in)-304.4(patients)-299.9(with)-303(sarcoidosis.)]TJ /F1 1 Tf -5.1349 -2.4864 TD [(First)-305.4(author)]TJ 0 -1.3526 TD [(\(reference)-309(number\))]TJ 11.2335 1.3526 TD [(The)-306.3(aim)-299.7(of)-297(the)-308.1(study)-296.2(regarding)]TJ 1.5469 -1.3526 TD [(the)-300(clinical)-305.2(utility)-297.7(of)-305.1(SAA)]TJ 16.0363 1.3526 TD (Diagnosis)Tj -0.243 -1.3526 TD [(\(number)-306.8(of)]TJ 0.5264 -1.3607 TD (patients\))Tj 7.5484 2.7132 TD [(Method)-300(used)]TJ 1.2959 -1.3526 TD [(for)-300.8(SAA)]TJ -0.6803 -1.3607 TD (measuring)Tj 16.2064 2.7132 TD [(Results)-303(/Comments)]TJ /F6 1 Tf -53.4705 -5.1753 TD [(Rothkrantz-Kos)-307.7(et)-300.5(al.)]TJ 0 -1.3607 TD (\()Tj 0 0 0 0.7 k 0.243 0 TD (66)Tj 0 0 0 1 k 1.1015 0 TD (\))Tj 9.5165 1.3607 TD [(To)-297.2(evaluate)-301.6(the)-304(clinical)-300.6(usefulness)]TJ 0 -1.3607 TD [(of)-299.5(SAA)-295.6(for)-303.4(assessing)-299.1(sarcoidosis)]TJ 0 -1.3525 TD (severity)Tj 16.1497 2.7132 TD (Sarcoidosis)Tj 0 -1.3607 TD [(\(n=144:)-307.1(73)]TJ 0 -1.3525 TD [(untreated)-307.5(+)-297.9(7)0(1)]TJ 0 -1.3607 TD (treated\))Tj 0 -1.3526 TD [(HC)-306.8(\(n=282\))]TJ 9.1277 5.4264 TD (Immunonephelo-)Tj 0 -1.3607 TD [(metric)-301.8(assay)]TJ /F19 1 Tf 8.0829 1.3607 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(does)-300.6(not)-302.6(correlate)-309(with)-294.9(the)-304(disease)-302.4(severity)-303.9(in)]TJ -1.9195 -1.3607 TD (sarcoidosis)Tj -44.2213 -5.4264 TD [(Miyoshi)-302.9(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.0986 0 TD (67)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3421.8(T)0(o)-297.2(identify)-306.1(marker)-298(predictive)-308.9(of)]TJ 3.6608 -1.3526 TD [(increased)-303.1(parenchymal)-299.4(in)]TJ /F7 1 Tf 10.869 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ltration)-301.5(in)]TJ -11.3064 -1.3607 TD (sarcoidosis)Tj 16.1497 2.7132 TD [(Sarcoidosis)-303.4(\(n=43\))-1173.6(Immunoturbidi-)]TJ 9.1277 -1.3526 TD [(metric)-301.8(assay)]TJ /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(concentration)-307(at)-300.5(diagnosis)-304.1(is)-299.7(not)-302.6(predictive)-300.8(of)]TJ -1.9195 -1.3526 TD [(increased)-303.1(parenchymal)-307.5(in)]TJ /F7 1 Tf 10.869 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ltration)-309.6(later)-297.7(in)-304.4(sarcoidosis)]TJ -55.5277 -2.7213 TD [(Salazar)-299.7(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.0015 0 TD (68)Tj 0 0 0 1 k 1.1096 0 TD [(\))-3510.9(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(as)-298.8(a)-299.9(marker)-306.1(of)]TJ 3.7499 -1.3526 TD [(disease)-302.4(activity)-302.9(in)-296.3(patients)-308(with)]TJ 0 -1.3606 TD (sarcoidosis)Tj 16.1497 2.7132 TD (Sarcoidosis)Tj 0 -1.3526 TD [(\(n=85:)-308.3(40)-297.2(active)-305.9(+)]TJ 0 -1.3606 TD [(45)-305.3(inactive\))]TJ 9.1277 2.7132 TD (ELISA)Tj /F19 1 Tf 8.0829 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-299.7(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(higher)-302.8(in)-304.4(sarcoidosis)-303.6(patients)-299.9(with)-303(active)]TJ -7.4026 -1.3526 TD [(disease)-302.4(than)-299.5(in)-304.4(those)-301.7(with)-303(inactive)-302.5(disease)]TJ -44.2213 -2.7132 TD [(Bargagli)-302.1(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.3578 0 TD (69)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3162.6(T)0(o)-297.2(investigate)-300.7(possible)-304.9(bene)]TJ /F7 1 Tf 15.5341 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ts)-307.2(of)]TJ -12.5699 -1.3607 TD [(SAA)-295.6(as)-298.8(a)-299.9(biomarker)-309.1(in)-296.3(sarcoidosis)]TJ 16.1497 1.3607 TD [(sarcoidosis)-303.6(\(n=55\))]TJ 0 -1.3607 TD [(HC)-306.8(\(n=24\))]TJ 9.1277 1.3607 TD (2-DE+western)Tj 0 -1.3607 TD (blot,)Tj 0 -1.3526 TD (ELISA)Tj /F19 1 Tf 8.0829 2.7132 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(and)-306.5(SAA1)-294.4(may)-307.7(be)-303(used)-297.3(as)-298.8(a)-299.9(diagnostic)-306.1(marker)-306.1(for)]TJ -1.9195 -1.3607 TD [(sarcoidosis,)-309(marker)-298(of)-299.5(disease)-302.4(activity)-302.9(and)-306.5(a)-299.9(predictor)-298.4(of)-307.6(severe)]TJ 0 -1.3526 TD [(disease)-302.4(\(requiring)-306.8(steroid)-298.1(therapy\))]TJ -44.2213 -1.3607 TD [(Gungor)-298.1(et)-308.6(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.1148 0 TD (70)Tj 0 0 0 1 k 1.1096 0 TD 3.3975 Tc [(\)T)3397.5(o)]TJ /F7 1 Tf 5.0377 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(a)-299.9(sensitive)-308.1(marker)-298(of)]TJ -1.8385 -1.3607 TD [(sarcoidosis)-303.6(disease)-302.4(activity)]TJ 16.1497 1.3607 TD [(Sarcoidosis)-303.4(\(n=48:)]TJ 0 -1.3607 TD [(37)-305.3(active)-297.8(+)-306(1)0(1)]TJ 0 -1.3526 TD (inactive\))Tj 0 -1.3607 TD [(HC)-306.8(\(n=20\))]TJ 9.1277 4.0739 TD (ELISA)Tj /F19 1 Tf 8.0829 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(can)-303.7(be)-303(used)-297.3(as)-306.9(a)-299.9(marker)-298(of)-299.5(sarcoidosis)-303.6(activity)-302.9(since)-303.8(it)]TJ -1.9195 -1.3607 TD [(correlates)-307.8(with)-294.9(disease)-302.4(activity)-311(\(better)-304.2(than)-299.5(CRP\))]TJ -44.2213 -4.0658 TD [(Zhang)-300.7(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 5.5965 0 TD (71)Tj 0 0 0 1 k 1.1015 0 TD 3.924 Tc [(\)T)3924(o)]TJ /F7 1 Tf 5.5641 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(a)-299.9(serum)-302.2(marker)-306.1(for)]TJ -1.8385 -1.3607 TD [(dif)67.6(ferential)-303.8(diagnosis)-304.1(of)-299.5(sarcoidosis)]TJ 0 -1.3526 TD [(from)-299.4(other)-298.6(lung)-298.6(diseases)]TJ 16.1497 2.7132 TD [(Sarcoidosis)-303.4(\(n=37\))]TJ 0 -1.3607 TD (Tuberculosis)Tj 0 -1.3526 TD (\(N=20\))Tj 0 -1.3606 TD [(Other)-306(pulmonary)]TJ T* (diseases\(n=20\))Tj 0 -1.3526 TD [(HC)-306.8(\(n=20\))]TJ 9.1277 6.7871 TD [(MALDI-TOF)-302.8(MS,)]TJ 0 -1.3607 TD (ELISA)Tj /F19 1 Tf 6.9999 0 0 6.9999 354.8976 487.6723 Tm ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(levels)-305.1(are)-304.1(signi)]TJ /F7 1 Tf 8.334 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(higher)-302.8(in)-304.4(sarcoidosis)-303.6(patients)]TJ -10.6909 -1.3607 TD [(compared)-305.2(to)-299(other)-306.7(lung)-298.6(diseases)-301.3(and)-306.5(can)-295.6(be)-303(used)-305.4(as)-298.8(a)]TJ 0 -1.3526 TD [(diagnostic)-306.1(marker)-298(for)-303.4(sarcoidosis)]TJ /F19 1 Tf 0 -1.3606 TD ()Tj /F6 1 Tf 1.9195 0 TD [(Truncated)-305.7(SAA)-295.6(forms)-306.4(might)-299.8(be)-303(an)-295.4(even)-307.4(more)-298.6(speci)]TJ /F7 1 Tf 21.9729 0 TD ()Tj /F6 1 Tf 0.4374 0 TD (c)Tj -24.3298 -1.3607 TD [(diagnostic)-306.1(marker)-298(for)-303.4(sarcoidosis)]TJ -44.2213 -2.7132 TD [(Enyedi)-303.4(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.7342 0 TD (72)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3786.3(T)0(o)-297.2(evaluate)-301.6(markers)-305(for)-303.4(dif)67.6(ferential)]TJ 4.0253 -1.3526 TD [(diagnosis)-296(of)-299.5(sarcoidosis)-303.6(from)-307.5(other)]TJ 0 -1.3607 TD [(lung)-298.6(diseases)]TJ 16.1497 2.7132 TD [(Sarcoidosis)-303.4(\(n=69\))]TJ 0 -1.3526 TD [(Other)-306(lung)]TJ 0 -1.3607 TD [(diseases)-309.4(\(n=35\))]TJ 9.1277 2.7132 TD (Immunonephelo-)Tj 0 -1.3526 TD [(metric)-301.8(assay)]TJ /F19 1 Tf 8.0829 1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(does)-300.6(not)-302.6(signi)]TJ /F7 1 Tf 8.1801 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(dif)59.5(fer)-296.8(between)-305.7(patients)-308(with)]TJ -10.537 -1.3526 TD [(biopsy-proven)-305.7(sarcoidosis)-303.6(and)-306.5(biopsy)-300.1(negative)-300.1(patients)]TJ ET 0 0 0 0.7 k 45.354 376.951 504.567 0.22678 re f 45.354 181.02 504.567 0.22676 re f 45.354 340.498 76.025 0.28348 re f 227.849 340.498 m 121.38 340.498 l 121.38 340.781 l 227.849 340.781 l f* 227.849 340.498 322.072 0.28348 re f BT /F1 1 Tf 6.9999 0 0 6.9999 45.3543 383.1873 Tm 0 0 0 1 k [(TABLE)-301(6)-428(|)]TJ /F6 1 Tf 5.1349 0 TD [(Characteristics)-305(and)-306.5(results)-298.7(of)-299.5(articles)-306.1(investigating)-303.9(clinical)-300.6(utility)-303.5(of)-299.5(SAA)-295.6(in)-304.4(patients)-299.9(with)-303(systemic)-307.5(sclerosis,)-299(systemic)-307.5(lupus)-301.8(erythematosus)-300.7(o)]TJ 59.0034 0 TD [(r)-302.3(psoriatic)-307.7(arthritis.)]TJ /F1 1 Tf -64.1383 -2.4864 TD [(First)-305.4(author)]TJ 0 -1.3607 TD [(\(reference)-309(number\))]TJ 10.8609 1.3607 TD [(The)-257.7(aim)-267.3(of)-264.6(the)-267.6(study)-263.8(regarding)]TJ 1.4416 -1.3607 TD [(the)-308.1(clinical)-297.1(utility)-305.8(of)-305.1(SAA)]TJ 13.9224 1.3607 TD (Number)Tj 1.4254 -1.3607 TD (of)Tj -1.4416 -1.3526 TD (patients)Tj 5.9772 2.7132 TD (Diagnosis)Tj -0.243 -1.3607 TD [(\(number)-306.8(of)]TJ 0.5264 -1.3526 TD (patients\))Tj 7.3945 2.7132 TD [(Method)-300(used)-301.8(for)]TJ 0.2673 -1.3607 TD [(SAA)-301.2(measuring)]TJ 15.8419 1.3607 TD [(Results)-303(/)-300.1(Comments)]TJ /F6 1 Tf -55.9731 -5.1834 TD [(Brandwein)-303.5(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 7.4512 0 TD (73)Tj 0 0 0 1 k 1.1015 0 TD [(\))-2069.3(T)0(o)-297.2(explore)-305.9(SAA)-295.6(as)-298.8(a)-299.9(marker)-306.1(of)]TJ 2.3083 -1.3526 TD [(SSc)-297.2(severity)]TJ 16.7004 1.3526 TD [(74)-2346.2(SSc)-297.2(\(n=62\))]TJ 3.4502 -1.3526 TD [(HC)-298.7(\(n=12\))]TJ 7.8643 1.3526 TD (Radioimmuno-assay)Tj /F19 1 Tf 10.6504 0 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(is)-299.7(signi)]TJ /F7 1 Tf 5.0539 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(correlated)-303.9(with)-303(SSc)-297.2(severity)]TJ -7.4026 -1.3526 TD [(\(assessed)-302.9(by)-298.3(extension)-305.5(of)-299.5(skin)-297.3(thickening\))]TJ -49.5262 -1.3607 TD [(Lakota)-305.2(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.799 0 TD (74)Tj 0 0 0 1 k 1.1015 0 TD [(\))-3721.5(T)0(o)-297.2(determine)-300.6(clinical)-308.7(correlations)]TJ 3.9605 -1.3526 TD [(of)-299.5(SAA)-295.6(in)-304.4(patients)-299.9(with)-303(SSc)]TJ 16.425 1.3526 TD [(227)-2069.6(SSc)-297.2(\(n=129\))]TJ 3.7256 -1.3526 TD [(HC)-298.7(\(n=98\))]TJ 7.8643 1.3526 TD (ELISA)Tj /F19 1 Tf 10.6504 0 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(signi)]TJ /F7 1 Tf 4.0982 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(correlates)-299.7(with)-303(pulmonary)]TJ -6.4469 -1.3526 TD [(function)-304.1(and)-298.4(is)-299.7(a)-299.9(sensitive)-300(marker)-306.1(of)-299.5(pulmonary)]TJ 0 -1.3607 TD [(involvement)-304.3(in)-296.3(SSc)]TJ -49.5262 -1.3526 TD [(Lis)-303.3(Swiety)-302(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 7.192 0 TD (75)Tj 0 0 0 1 k 1.1015 0 TD [(\))-2328.4(T)0(o)-297.2(evaluate)-301.6(SAA)-303.7(in)-296.3(SSc)-305.3(patients)]TJ 2.5674 -1.3607 TD [(in)-296.3(relation)-301.2(to)-299(skin)-305.4(and)-298.4(pulmonary)]TJ T* (involvement)Tj 16.7004 2.7213 TD [(48)-2346.2(SSc)-297.2(\(n=33:)-308.3(18)]TJ 3.4502 -1.3607 TD [(early)-300.8(dSSc)-300.3(+)-306(1)0(5)]TJ T* [(late)-301.9(dSSc\))]TJ 0 -1.3526 TD [(HC)-298.7(\(n=15\))]TJ 7.8643 4.0739 TD (ELISA)Tj /F19 1 Tf 10.6504 0 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(is)-299.7(superior)-305(to)-299(CRP)-304.1(as)-298.8(a)-299.9(biomarker)-301(of)]TJ -1.9114 -1.3607 TD [(pulmonary)-305.5(involvement)-304.3(in)-296.3(SSc)]TJ -49.5262 -4.0739 TD [(Wang)-303.4(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.4021 0 TD (76)Tj 0 0 0 1 k 1.1015 0 TD [(\))-4118.3(T)0(o)-297.2(investigate)-300.7(correlation)]TJ 4.3573 -1.3526 TD [(between)-297.6(SAA)-303.7(levels)-297(and)-306.5(disease)]TJ 0 -1.3606 TD [(activity)-302.9(in)-296.3(SLE)]TJ 16.425 2.7132 TD [(284)-2069.6(SLE)-302(\(n=135:)-299(52)]TJ 3.7256 -1.3526 TD [(active)-305.9(+)-297.9(8)0(3)]TJ 0 -1.3606 TD [(inactive)-302.5(disease\))]TJ 0 -1.3526 TD [(HC)-298.7(\(n=149\))]TJ 7.8643 4.0658 TD (Immunonephelometric)Tj 0 -1.3526 TD (assay)Tj /F19 1 Tf 10.6504 1.3526 TD ()Tj /F6 1 Tf 1.9114 0 TD [(SAA)-303.7(is)-299.7(independently)-302.6(signi)]TJ /F7 1 Tf 11.2983 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(correlated)]TJ -13.647 -1.3526 TD 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[(acute)-304.6(febrile)-302.5(respiratory)-301.7(infection)]TJ -45.8087 -4.0739 TD [(Bilginer)-299.7(et)-300.5(al.)-306.5(\()]TJ 0 0 0 0.7 k 6.0015 0 TD (85)Tj 0 0 0 1 k 1.1096 0 TD 3.5109 Tc [(\)T)3510.9(o)]TJ /F7 1 Tf 5.151 0 TD 0 Tc ()Tj /F6 1 Tf 0.4374 0 TD [(nd)-298.2(biomarkers)-308(for)]TJ -1.8385 -1.3607 TD [(predicting)-299.2(atherosclerosis)-309.1(in)]TJ 0 -1.3526 TD [(FMF)-294.7(patients)]TJ 14.2302 2.7132 TD [(FMF)-294.7(\(n=70,)-308.3(attack-)]TJ 0 -1.3607 TD [(free)-297(period\))]TJ 0 -1.3526 TD [(HC)-298.7(\(n=50\))]TJ 10.3669 2.7132 TD (ELISA)Tj /F19 1 Tf 10.3507 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-299.7(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(cantly)-301.1(higher)-302.8(in)-296.3(FMF)-302.8(patients)-308(even)-299.3(in)-296.3(attack-)]TJ -7.4026 -1.3607 TD [(free)-305.1(periods)-300.6(compared)-305.2(to)-299(HC)]TJ /F19 1 Tf 0 -1.3526 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(is)-299.7(signi)]TJ /F7 1 Tf 5.0458 0 TD ()Tj /F6 1 Tf 0.4374 0 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12.9021 0 TD 0.0521 Tc (180)Tj 0 0 0 1 k 1.5874 0 TD 0.0496 Tc [(\).)-555.9(The)-560.8(e)0.1(arliest)-561.4(p)2.7(hase)-560.8(of)]TJ -14.4895 -1.2114 TD 0 Tc [(at)22.9(he)16(r)11.9(o)0(g)21.1(e)0(n)20.1(e)0(s)16.1(i)15.3(s)-292.4(i)0(n)19.2(v)0(o)21.1(l)0(v)21.7(e)0(s)-282.2(v)0(a)17.8(s)11.9(cu)22.9(la)18.6(r)-292.4(e)0(n)20.1(d)12.7(ot)20.2(he)16(li)20.7(a)13.3(l)-293.1(ce)20.4(ll)-275.8(\(E)15.8(C\))-278.1(dy)17.2(s)11.9(f)0(u)17.3(n)0(c)20.1(t)0(i)24.9(o)0(n)20.5(.)]TJ T* [(Th)23.1(e)-413.5(S)0(A)15.2(A)12.7(-i)17.2(nd)22.6(uc)17(ed)-400.8(pr)18.7(o-)18.5(i)15.3(n)]TJ /F12 1 Tf 10.1331 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(a)13.3(m)0(m)18.7(a)13.3(to)20.2(ry)-407.3(cy)20.6(to)20.2(k)11.6(i)0(n)19.2(e)-413.5(TN)22.2(F)]TJ /F17 1 Tf 10.0316 0 TD (a)Tj /F11 1 Tf 1.0324 0 TD [(st)15.5(i)15.3(m)0(u)19.1(l)0(a)18.6(t)0(e)19.8(s)]TJ -21.7223 -1.2114 TD [(th)21.4(e)-324(e)0(x)18.7(p)0(r)18.7(e)0(s)22.1(s)0(i)15.3(o)0(n)-313.7(o)0(f)-313(a)0(d)20.1(h)0(e)16(s)11.9(io)20(n)-324.3(m)0(o)17(l)0(e)21.5(c)0(u)22.9(l)0(e)15.5(s)-322.3(on)-313.7(EC)18.5(s)-328.2(a)13.3(nd)-317.5(s)11.9(t)0(i)18.9(m)12.3(ul)18.1(at)22.9(es)-318(th)21.4(e)]TJ 0 -1.2055 TD [(pr)18.7(od)23.4(uc)17(ti)18.9(on)-242(of)-241.4(ti)18.9(s)11.9(s)0(u)18.7(e)-252.4(fa)17.8(ct)19.8(or)-246(\()14.8(T)0(F)18(\))-253.8(wh)20.4(ic)19.6(h)-256.7(p)12.8(r)11.9(o)0(m)17(o)0(t)20.2(e)0(s)-240.5(t)0(h)15.4(e)-252.4(fo)21.2(r)11.9(m)0(a)19.7(t)0(i)18.9(o)0(n)-242.1(o)0(f)]TJ 0 -1.2114 TD 0.0102 Tc [(atherosclerotic)-516.7(p)-0.9(laque)-516.7(\()]TJ 0 0 0 0.7 k 10.0913 0 TD (181)Tj 0 0 0 1 k 1.468 0 TD 0 Tc (,)Tj 0 0 0 0.7 k 0.7519 0 TD [(18)-14.7(2)]TJ 0 0 0 1 k 1.4621 0 TD 0.0094 Tc [(\).)-524.5(SAA-tr)9.4(e)-10.3(a)-1.2(ted)-520.9(E)-1.5(Cs)-521.8(s)9.4(h)-8.7(ow)-525(a)]TJ -13.7734 -1.2114 TD 0 Tc (signi)Tj /F12 1 Tf 1.8798 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(cantly)-502.3(increased)-503.1(expressi)9.1(on)-504.6(of)-510(TNF)]TJ /F17 1 Tf 15.0206 0 TD (a)Tj /F11 1 Tf 0.6266 0 TD [(,)-504.1(T)0(F)-507.1(and)-507.1(vascular)]TJ -18.0522 -1.2114 TD 0.026 Tc [(endothelial)-535.6(g)0.6(rowth)-535.1(f)0.7(actor)-535(\()-1(VEGF\))-538.1(\()]TJ 0 0 0 0.7 k 16.0053 0 TD 0.0223 Tc [(18)-6(3)]TJ 0 0 0 1 k 1.5158 0 TD 0.024 Tc [(\).)-539.8(P)-4.8(h)0(a)-4.5(r)0.1(ma)-4.5(cologi)-2.4(c)-7.6(a)1.5(l)]TJ -17.521 -1.2114 TD 0.0144 Tc [(bl)-4.1(ock)-3.9(a)-2.1(de)-524.4(of)-530.1(SAA)-527.9(r)-3.5(ec)-5.2(eptors,)-531.5(i)-0.1(ncl)-4.1(u)3.3(din)-5.6(g)-524.2(FPRL1,)-531.5(TLR2/4)-527.1(an)-5.6(d)]TJ T* 0 Tc [(RA)17.9(GE)16.8(,)-492.2(i)0(n)13.3(h)11.8(ib)20(it)13(s)-489.4(S)0(A)15.2(A)0(-)20.5(m)0(e)16.6(d)0(i)16.1(a)0(t)16.9(e)0(d)-484.3(p)0(r)18.7(o)0(-)12.6(a)13.3(th)15.4(er)16.1(og)21.1(en)14.1(ic)-481.7(ef)80.4(fe)14.8(ct)13.8(s)-489.4(i)0(n)-482(E)0(C)12.5(s)11.9(.)]TJ T* 0.0127 Tc [(However,)-527.2(the)-526.1(p)1.6(h)-5.3(a)2.1(rm)-4.8(acological)]TJ 13.5525 0 TD [(inhibition)-526.4(is)-524.4(only)-525.9(partial)-519.1(i)-1.8(n)]TJ -13.5525 -1.2055 TD 0.0472 Tc [(contrast)-557.9(to)-562.8(adding)-557(isolated)-560.7(human)-563.6(H)1.6(DL)-555.7(which)-555.7(a)-5.1(l)4.8(m)-6.1(ost)]TJ 0 -1.2114 TD 0.0145 Tc [(complete)-5.1(ly)-524.1(abrogates)-528.6(S)-0.9(AA-induced)-527.7(pro-athero)-4.7(genic)-530.3(a)3.9(c)-5.1(t)0.2(ivity)]TJ T* 0 Tc (\()Tj 0 0 0 0.7 k 0.37 0 TD 0.0223 Tc [(18)-6(3)]TJ 0 0 0 1 k 1.5098 0 TD 0 Tc (,)Tj 0 0 0 0.7 k 0.7818 0 TD 0.0283 Tc [(18)6(4)]TJ 0 0 0 1 k 1.5158 0 TD 0.0248 Tc [(\).)-539(HDL)-536.3(r)-5.1(educes)-536.2(SAA)]TJ /F13 1 Tf 9.4289 0 TD 0 Tc ()Tj /F11 1 Tf 0.2447 0 TD 0.0258 Tc [(s)-535.2(b)0.6(ioavailability,)-532(b)0.6(ut)-537.5(oth)-4.2(e)0.2(r)]TJ 13.6003 36.3132 TD 0 Tc [(m)12.3(e)0(c)20.4(h)0(a)19.1(n)0(i)19.2(s)11.9(ms)-477.1(fo)21.2(r)-489.4(m)12.3(od)17.4(u)12.7(l)0(a)18.6(t)0(i)18.9(n)0(g)-475(S)0(A)21.1(A)-488.6(pr)18.7(o-)24.5(at)16.9(h)11.8(e)0(r)16.1(o)0(g)21.1(e)0(n)20.1(i)15.3(c)-491.1(a)13.3(ct)19.8(iv)19.8(it)18.9(ie)19.6(s)-483.4(i)0(n)]TJ 0 -1.2114 TD [(E)13(C)-239.1(ar)19.2(e)-240.4(a)13.3(ls)17.2(o)-234(p)0(o)17.4(s)11.9(s)11.9(i)0(b)20(l)0(e)21.5(.)-241.5(F)12.7(o)0(r)-228.1(i)0(n)19.2(s)11.9(ta)16.9(nc)20.1(e,)-225.3(ci)19.6(rc)16.1(u)12.8(l)0(a)18.6(t)0(i)18.9(n)0(g)-224.4(H)0(D)21(L)-238.8(m)12.3(a)0(y)-232.9(i)15.3(nd)16.7(ir)21.3(ec)20.4(tl)20.9(y)]TJ 0 -1.2055 TD [(in)19.2(a)13.3(c)0(t)19.8(i)0(v)19.8(a)0(t)16.9(e)-485.1(m)12.3(e)0(m)22.5(b)0(r)16.6(a)13.3(ne)-475.2(SA)21.1(A)-488.6(r)11.9(ec)20.4(ep)17(to)20.2(r)11.9(s)-483.4(by)-474.2(me)16.6(m)12.3(b)0(r)22.6(a)0(n)17.2(e)-485.1(ch)22(ol)21.9(es)16.1(te)19.8(r)11.9(o)0(l)]TJ 0 -1.2114 TD [(le)21.5(ve)20.6(l)-299(m)12.3(od)17.4(u)12.7(l)0(a)18.6(t)0(i)24.9(o)0(n)-289.8(\()]TJ 0 0 0 0.7 k 7.2268 0 TD -0.0135 Tc [(18)-13.5(5)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc [(\).)-286.4(Th)17.1(er)22.1(ef)20.7(or)16.6(e,)-285(SA)21.1(A)12.6(:)0(H)17.2(D)12.9(L)-298.5(b)0(l)21.9(o)0(o)21.3(d)-297.6(r)11.9(a)0(t)16.9(i)0(o)-284.3(m)12.3(ay)-286.6(be)]TJ -8.6292 -1.2114 TD [(of)-205.6(a)-213.5(c)0(r)22.1(i)0(t)18.9(i)0(c)19.6(a)13.3(l)-215.5(i)0(m)21.7(p)0(o)17.4(r)11.9(ta)16.9(nc)20.1(e)-210.6(f)0(o)15.2(r)-214.9(H)14(D)0(L)]TJ /F13 1 Tf 12.5261 0 TD ()Tj /F11 1 Tf 0.2089 0 TD [(s)-214.9(a)13.3(bi)20(li)20.7(ty)-206.8(to)-200.6(pr)18.7(ot)20.2(ec)20.4(t)-211.2(E)0(C)18.5(s)-214.9(fr)16.5(om)-203.8(S)14.5(A)0(A)]TJ -12.735 -1.2114 TD [(pr)12.7(o-a)13.9(the)13.7(rog)15.1(eni)17.5(c)-503(a)0(c)11.6(t)0(i)13(vit)11.5(ie)13.6(s.)-498.2(Fur)13.5(the)13.7(rm)12.3(ore)14.9(,)-498.1(SAA)-491.4(up-)15.5(reg)14.6(ul)12.1(ate)15.2(s)-501.3(the)]TJ T* [(ex)18.7(p)12.8(r)0(e)16.1(s)11.9(s)11.9(i)0(o)20(n)-413.8(of)-396.6(TL)17.1(R2)-398.9(in)-398.5(EC)18.5(,)-408.6(s)11.9(ug)17.2(ge)20.6(s)11.9(t)0(i)18.9(n)0(g)-403.4(a)-410.4(p)12.8(o)0(s)22.6(i)0(t)18.9(i)0(v)19.8(e)-407.5(fe)14.7(ed)22.9(ba)18(ck)-401.9(lo)21.9(op)]TJ T* (\()Tj 0 0 0 0.7 k 0.3342 0 TD -0.0135 Tc [(18)-13.5(6)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc [(\).)-310.3(On)-307.4(to)20.2(p)-321.4(o)0(f)-307.1(a)0(l)18.6(l)-316.9(th)21.4(at)16.9(,)-319.1(S)14.5(AA)-308.9(si)15.3(gn)20.3(i)]TJ /F12 1 Tf 12.4545 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(ca)23.5(nt)19.5(ly)-306.5(de)17(cr)22.1(ea)17.5(s)11.9(e)0(s)-312.1(e)0(n)20.1(d)12.7(ot)20.2(h)11.8(e)0(l)15.5(i)0(a)22.7(l)]TJ -14.7162 -1.2114 TD [(ni)13.3(tr)15.5(ic)-481.7(ox)13.2(id)16.1(e)-497.1(\()0(N)19.8(O)0(\))-487.5(s)0(y)16.4(n)0(t)13.5(h)0(a)13.2(s)11.9(e)-497.1(l)0(e)15.5(v)0(e)14.7(l)0(s)17.2(,)-492.2(NO)-491.3(bi)20(oa)12(va)17.8(il)14.7(ab)18(il)14.7(it)18.9(y)-496.8(a)0(n)17.2(d)-494.5(th)15.4(e)]TJ 0 -1.2055 TD [(a)13.3(c)0(t)19.8(i)0(v)19.8(i)0(t)18.9(y)-353.6(of)-336.9(in)19.2(te)19.8(rn)15.8(a)13.3(l)-352.7(a)13.3(n)0(t)19.5(i)0(o)20(x)0(i)17.8(d)12.7(an)17.2(t)-348.5(e)0(n)20.1(z)0(y)20.6(m)0(e)16.6(s)-352.1(ca)23.5(ta)16.9(la)18.6(s)11.9(e)-353.8(a)13.3(n)0(d)-341.4(s)0(u)18.7(p)0(e)17(r)11.9(ox)19.1(id)22.1(e)]TJ 0 -1.2114 TD [(di)16.1(sm)12.3(ut)16.4(as)13.3(e)-491.1(i)0(n)-488(E)0(C)12.5(s)11.9(,)-498.1(l)0(e)15.5(a)0(d)14.1(i)0(n)13.3(g)-490.9(to)-487(an)-490(in)19.2(cre)20.4(as)13.3(ed)-484.3(su)12.7(pe)17(rox)19.1(id)16.1(e)-497.1(r)11.9(ad)14.1(ic)13.6(al)]TJ T* [(a)-10.6(n)-8(i)-8.5(o)-7.3(n)-533.2(p)-11.1(ro)-13.2(d)-11.1(u)-11.1(c)-7.7(t)-14.3(i)-8.5(o)-7.3(n)-8(,)-528(i)-14.5(mp)-16.7(a)-10.6(i)-8.5(r)-12(e)-7.7(d)-530.3(N)-7(O)-532.1(a)-10.6(c)-7.7(t)-8.3(i)-8.5(v)-7.5(i)-14.5(t)-8.3(y)-526.7(a)-10.6(n)-8(d)-11.1(,)-528(c)-13.7(o)-7.3(n)-8(s)-12(e)-7.7(q)-9.2(u)-11.1(e)-7.7(n)-8(t)-14.3(l)-6.6(y)-7.5(,)]TJ T* [(endothelial)-506.3(dysfunction)-502.8(and)-513.1(atherosclero)8.3(tic)-507.9(plaque)-509.9(formation)]TJ T* (\()Tj 0 0 0 0.7 k 0.37 0 TD 0.0283 Tc [(18)6(7)]TJ 0 0 0 1 k 1.5158 0 TD 0.0265 Tc [(\).)-537.3(I)-4.5(n)0.6(tri)-5.9(g)1.1(uingly)-4.8(,)-537.3(a)-2(theroscle)-5.1(r)2.6(oti)-5.9(c)-536.2(cardiov)-4.8(a)4(scular)-540.5(diseases)]TJ -1.8858 -1.2114 TD 0 Tc [(ar)-10.6(e)-526.9(t)-8.3(he)-527(pr)-11.2(i)-8.5(m)0(a)-16.1(r)0(y)-526.7(c)-7.7(au)-15.7(se)-526.9(o)-7.3(f)-526.6(pr)-11.2(e)-7.7(m)0(a)-16.1(t)0(u)-13.5(r)0(e)-526.9(d)0(e)-12.9(a)-10.6(th)-527.6(i)-8.5(n)-521.2(pa)-15.7(ti)-10.9(e)-7.7(n)-8(ts)-527.5(w)-9.3(i)0(t)-10.9(h)]TJ 0 -1.2055 TD -0.0137 Tc [(rh)-13.7(euma)-13.7(ti)-13.7(c)-292.5(d)-13.7(i)8.4(s)-13.7(eas)-13.7(e)2.4(s.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 210.8409 Tm 0 Tc [(SAA)-301.8(IN)-302.3(RHEUMATOID)-301.2(ARTHRITIS)]TJ /F11 1 Tf 9.5 0 0 9.5 306.1417 190.8283 Tm [(SAA)-306.4(can)-300.8(be)-301.4(used)-310.5(as)-303(a)-303(diagnostic)-304.4(marker)-304.7(for)-307.1(RA)-304.3(since)-306.5(its)-303.3(serum)]TJ 0 -1.2114 TD [(le)-8.3(ve)-9.2(ls)-507.9(ar)-10.6(e)-503(s)0(i)-8.6(g)-7.5(ni)]TJ /F12 1 Tf 6.3138 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(can)-14.4(tly)-511.8(el)-8.3(ev)-9.2(at)-7(ed)-508.2(i)-8.5(n)-503.3(R)-6.6(A)-506.5(pa)-9.8(tie)-12.6(nts)-511.7(c)-7.7(o)0(m)-6.9(p)0(a)-9.8(r)0(e)-7.7(d)-506.4(to)]TJ -6.8509 -1.2114 TD [(healthy)-458.7(controls)-463(and)-459.4(patients)-462.5(with)-455.9(osteoarthritis)-463(\(OA\))-460.1(\()]TJ 0 0 0 0.7 k 23.5185 0 TD (5)Tj 0 0 0 1 k 0.4774 0 TD (,)Tj 0 0 0 0.7 k 0.6743 0 TD (9)Tj /F13 1 Tf 0 0 0 1 k 0.4774 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k -25.1477 -1.2114 TD (11)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-214.8(SAA)-216.9(levels)-215.2(are)-221.2(increased)-216.6(in)-219.5(RA)-214.8(compared)-222.2(to)-212.5(OA)-221.1(patients)-217.8(not)]TJ -0.9608 -1.2114 TD [(only)-262.1(in)-255.3(the)-260.8(serum,)-260(but)-259.4(also)-263.2(in)-261.2(synovial)]TJ /F12 1 Tf 15.5159 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(uid,)-260.4(as)-261.2(a)-261.2(result)-260.6(of)-259.3(a)-255.2(local)]TJ -16.047 -1.2055 TD [(production)-265.5(\()]TJ 0 0 0 0.7 k 5.0486 0 TD (12)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.4774 0 TD (20)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.4774 0 TD (29)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-262.5(A)-255.9(number)-260.5(of)-259.3(researches)-268.4(demonstrated)-264.8(a)]TJ -8.8799 -1.2114 TD (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-428.5(correlation)-430.1(between)-426(SAA)-431.7(serum)-430.3(concentration)-431.7(and)]TJ -2.4169 -1.2114 TD [(RA)-238.7(disease)-248.6(activity)-240(\()]TJ 0 0 0 0.7 k 8.0444 0 TD (9)Tj 0 0 0 1 k 0.4774 0 TD (,)Tj 0 0 0 0.7 k 0.4595 0 TD (10)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.4595 0 TD (13)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-238.7(SAA)-246.7(is)-241.3(a)-237.3(more)-241.4(sensitive)-247.4(marker)-239.1(of)]TJ -11.3564 -1.2114 TD [(disease)-385.9(activity)-383.3(in)-386.6(RA)-381.9(than)-385.1(CRP)-382(or)-383.2(ESR)-385(\()]TJ 0 0 0 0.7 k 17.336 0 TD (11)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.6027 0 TD (14)Tj /F13 1 Tf 0 0 0 1 k 0.9548 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5132 0 TD (16)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.6027 0 TD (21)Tj 0 0 0 1 k 0.9548 0 TD [(\),)-387.9(even)]TJ -22.88 -1.2114 TD [(during)-213.4(pregnancy)-217.3(\()]TJ 0 0 0 0.7 k 7.5909 0 TD (17)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-214.8(Chambers)-216.7(et)-213(al.)-211(were)-215.7(the)]TJ /F12 1 Tf 10.6702 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rst)-211.3(to)-212.5(report)-213.5(an)]TJ -19.747 -1.2114 TD [(increased)-359.8(SAA)-360.1(level)-358.4(in)-356.7(RA)-358(patients)-361(with)-360.5(normal)-354.4(CRP)-358.1(levels)-364.4(in)]TJ ET 0 0 0 0.7 k 45.354 442.828 504.567 0.22678 re f 45.354 706.053 504.567 0.28351 re f 45.354 668.806 504.567 0.22675 re f BT /F1 1 Tf 6.9999 0 0 6.9999 45.3543 712.2896 Tm 0 0 0 1 k [(TABLE)-301(7)-428(|)]TJ /F6 1 Tf 5.1349 0 TD (Continued)Tj /F1 1 Tf -5.1349 -2.6079 TD [(First)-305.4(author)]TJ 0 -1.3526 TD [(\(reference)-309(number\))]TJ 12.7075 1.3526 TD [(The)-298.2(aim)-299.7(of)-305.1(the)-300(study)]TJ -1.5631 -1.3526 TD [(regarding)-308.7(the)-300(clinical)-305.2(utility)]TJ 4.7866 -1.3607 TD [(of)-297(SAA)]TJ 9.476 2.7132 TD [(Diagnosis)-300.9(\(number)]TJ 1.7818 -1.3526 TD [(of)-297(patients\))]TJ 9.1115 1.3526 TD [(Method)-300(used)-301.8(for)]TJ 0.2673 -1.3526 TD [(SAA)-301.2(measuring)]TJ 17.5427 1.3526 TD [(Results)-311.1(/)-300.1(Comments)]TJ /F19 1 Tf -8.3016 -5.1754 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(levels)-305.1(>150mg/L)-302.6(are)-295.9(associated)-310.1(with)-303(ocular,)-296.7(skin)]TJ -1.9195 -1.3606 TD [(and)-298.4(mucosal)-306.7(involvement)-304.3(in)-296.3(BD)]TJ -45.8087 -1.3526 TD [(Lee)-303.7(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 4.4545 0 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[(in)-296.3(amyloid)-303.8(load)-302.9(and)-306.5(long-term)-303.1(survival)-299.7(in)-296.3(patients)-308(with)]TJ T* [(secondary)-304.1(amyloidosis)]TJ -45.4199 -1.3526 TD [(Perry)-301.9(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 5.1187 0 TD (104)Tj 0 0 0 1 k 1.6522 0 TD [(\))-3851.1(T)0(o)-297.2(investigate)-300.7(the)-304(ef)63.5(fect)-301.8(of)]TJ 4.0901 -1.3607 TD [(etanercept)-304.5(on)-293.9(SAA)-303.7(levels)-305.1(in)]TJ 0 -1.3526 TD [(patients)-299.9(with)-303(amyloidosis)]TJ 14.1897 2.7132 TD [(AA)-297(amyloidosis)-301.5(\(n=9,)]TJ 0 -1.3607 TD [(dif)67.6(ferent)-301.2(underlying)]TJ 0 -1.3526 TD (diseases\))Tj 12.2783 2.7132 TD (ND)Tj /F19 1 Tf 8.091 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(SAA)-295.6(serum)-302.2(levels)-305.1(may)-299.6(be)-303(used)-297.3(for)-303.4(monitoring)-305.9(response)]TJ -1.9195 -1.3607 TD [(to)-299(etanercept)-304.5(in)-304.4(patients)-299.9(with)-303(AA)-297(amyloidosis)]TJ -45.4199 -2.7132 TD [(Nakamura)-305.6(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 7.2973 0 TD (105)Tj 0 0 0 1 k 1.6522 0 TD [(\))-1672.4(T)0(o)-297.2(investigate)-300.7(etanercept)]TJ 1.9114 -1.3526 TD [(ef)63.5(fects)-300.7(on)-302(SAA)-295.6(levels)-305.1(and)]TJ 0 -1.3607 TD [(disease)-302.4(activity)-302.9(in)-296.3(amyloidosis)]TJ 14.1897 2.7132 TD [(RA)-296.4(with)-303(amyloidosis)]TJ 0 -1.3526 TD (\(n=14\))Tj 12.2783 1.3526 TD (ND)Tj /F19 1 Tf 8.091 0 TD ()Tj /F6 1 Tf 1.9195 0 TD [(Etanercept)-304.4(induced)-298.4(SAA)-303.7(decrease)-298.7(is)-299.7(followed)-310.1(by)]TJ -1.9195 -1.3526 TD [(decrease)-306.8(in)-296.3(disease)-302.4(activity)-302.9(in)-304.4(amyloidosis)-301.5(patients,)-305.3(therefore)]TJ 0 -1.3607 TD [(SAA)-295.6(may)-307.7(be)-294.9(used)-305.4(for)-303.4(monitoring)-297.8(response)-307.1(to)-299(etanercept)]TJ -45.4199 -1.3607 TD [(Mijagawa)-303.7(et)-300.5(al.)-298.4(\()]TJ 0 0 0 0.7 k 6.9005 0 TD (106)Tj 0 0 0 1 k 1.6522 0 TD [(\))-2069.3(T)0(o)-297.2(assess)-303.7(ef)63.5(fects)-300.7(of)]TJ 2.3083 -1.3526 TD 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1.0145 0 TD 0.0274 Tc [(\).)-530.4(Wild)-526.8(et)-529.9(al.)-530.4(\()]TJ 0 0 0 0.7 k 6.9702 0 TD 0.0283 Tc (19)Tj 0 0 0 1 k 1.0145 0 TD 0 Tc (\))Tj -25.3148 -1.2114 TD [(performed)-392.1(a)-386.5(multivariate)-391.8(analysis)-386.1(of)-390.6(32)-384.7(biomarkers)-393.5(\(including)]TJ T* [(SAA)-503.3(and)-501.2(CRP\),)-507.3(out)-498.1(of)-504(131)-502.5(initially)-502.9(considered,)-513.7(which)-503.2(were)]TJ T* [(su)-11.2(b)-7.3(j)0(e)-8.3(c)-7.7(te)-10.1(d)-512.4(t)0(o)-510.9(t)-8.3(hr)-12.1(ee)-516.7(in)-10.6(c)-7.7(lus)-11.8(i)-8.5(o)-7.2(n)-509.3(c)0(r)-7.7(i)-8.5(te)-10.1(ri)-8.6(a)-10.6(:)-510.1(di)-7.7(sc)-13.7(ri)-8.6(m)-11.5(i)0(n)-10.6(a)0(t)-7(i)-8.5(on)-516.6(be)-9(tw)-11.6(ee)-9.4(n)]TJ 0 -1.2055 TD [(RA)-364(patients)-361(and)-363.9(healthy)-363.2(controls,)-364.3(ability)-367.6(to)-361.7(identify)-365.5(anti-cyclic)]TJ 0 -1.2114 TD [(citrullinated)-359.9(peptide)-364(antibody)-361(\(anti-CCP\))-361.9(negative)-358.3(RA)-358(patients)]TJ T* [(and)-363.9(speci)]TJ /F12 1 Tf 3.8372 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(city)-360.3(for)-360.8(RA.)-360.8(Among)-361.8(the)-362.3(tested)-359.5(biomarkers,)-366.4(only)-363.6(the)]TJ -4.3683 -1.2114 TD [(combination)-367.6(of)-366.7(SAA)-366(and)-363.9(anti-CCP)-367.6(increased)-365.8(the)-368.2(sensitivity)-365.4(of)]TJ T* [(anti-CCP)-206.5(alone)-213.2(\(80.1%)-206(vs.)-207.2(75.8%,)-211.7(respectively\),)-211.7(although)-206.8(this)-208(was)]TJ T* [(followed)-403.4(by)-408.6(a)-404.4(drop)-405.5(in)-404.5(speci)]TJ /F12 1 Tf 11.5056 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(city)-408(\(94%)-401.7(for)-408.5(anti-CCP)-403.4(alone)-410.2(vs.)]TJ 15.4145 31.4734 TD [(86.6%)-352.1(for)-348.9(SAA+)-355(anti-CCP\).)-355.6(Moreover,)-354.8(SAA)-354.1(is)-348.7(incorporated)-362.2(in)]TJ 0 -1.2114 TD [(the)-392.1(widely)-390.9(used)-388(multi-biomarker)-395.9(disease)-391.8(activity)-395.2(\(MBDA\))-392.6(test)]TJ 0 -1.2055 TD [(developed)-310.6(by)-307.1(Centola)-311.5(et)-302.5(al.)-312.4(\()]TJ 0 0 0 0.7 k 11.5832 0 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[(SAA)-336.2(has)-339(also)-340.7(been)-335(correlated)-347.5(with)-336.6(cardiovascular)-344(disease)-344.1(in)]TJ -1.2651 -1.2114 TD [(RA)-334.1(patients.)-340(Wong)-337.8(et)-338.3(al.)-330.3(\()]TJ 0 0 0 0.7 k 10.7776 0 TD (26)Tj 0 0 0 1 k 0.9608 0 TD [(\))-331.3(found)-337.3(that)-337.7(the)-338.4(decreased)-338.2(arterial)]TJ -11.7384 -1.2114 TD [(elasticity)-354.3(in)-356.7(RA)-352(patients,)-363.8(which)-354(may)-351.8(precede)-357.4(atherosclerosis,)-361.2(is)]TJ T* 0.0254 Tc (signi)Tj /F12 1 Tf 2.0111 0 TD 0 Tc ()Tj /F11 1 Tf 0.561 0 TD 0.0261 Tc [(cantly)-524.4(inversely)-530.4(c)0.5(orrelated)-522.1(w)-1.1(ith)-529(S)4.7(AA)-528.2(concentration.)]TJ -2.5721 -1.2114 TD 0 Tc [(Another)-484.3(study)-485.6(reported)-488.9(a)-488(trend)-482.8(of)-486.1(association)-488.6(between)-485.7(SAA)]TJ T* [(levels)-376.3(and)-381.8(severity)-381.5(of)-378.7(coronary)-376.6(atherosclerosis)-382.3(in)-380.6(patients)-378.9(with)]TJ ET 0 0 0 0.7 k 45.354 717.505 m 549.921 717.505 l 549.694 717.222 l 45.581 717.222 l f* 549.921 717.505 m 549.921 400.309 l 549.694 400.535 l 549.694 717.222 l f* 549.921 400.309 m 45.354 400.309 l 45.581 400.535 l 549.694 400.535 l f* 45.354 400.309 m 45.354 717.505 l 45.581 717.222 l 45.581 400.535 l f* q 311.962891 0 0 215.659775 141.732254 484.100677 cm /Im2 Do Q BT /F1 1 Tf 6.9999 0 0 6.9999 50.6268 463.0676 Tm 0 0 0 1 k [(FIGURE)-299.4(2)]TJ /F6 1 Tf 5.0053 0 TD [(|)-429.9(SAA)-303.7(signal)-295.4(transduction)-309.6(pathways)-299.8(and)-306.5(feedback)-301.9(loops)-300.3(with)-303(relevance)-305.1(for)-295.3(rheumatic)-309.2(diseases.)-298.6(SAA)-303.7(activates)-305.6(several)-299.9(cell)-302.6(receptors)-301.3(including)-299.8(Toll-l)]TJ 62.4509 0 TD (ike)Tj -67.4561 -1.3607 TD [(receptors)-301.3(2)-298.4(and)-306.5(4)-298.4(\(TLR2,)-300.1(TLR4\),)-300.1(formyl)-304.3(peptide)-303(receptor)-302.5(-like)-304.9(1)-298.4(\(FPRL1\),)-307.6(scavenger)-301.3(receptor)-302.5(class)-299.1(B)-305.9(type)-299.1(1)-298.4(\(SRB1\))-301.3(and)-306.5(receptors)-301.3(of)-299.5(advanced)-305.9(glycation)-299.8(e)]TJ 65.9429 0 TD (nd)Tj -65.9429 -1.3526 TD [(products)-303.6(\(RAGE\).)-299.9(SAA)-303.7(receptors)-301.3(share)-298.4(common)-309.3(properties)-305.3(in)-296.3(activating)-301.8(protein)-302.8(kinases)-304.8(\(MAPKs\))-302.8(and)-298.4(transcription)-311.1(factors)-295.2(such)-305.9(as)-298.8(nuclear)-304.5(factor)-304.5(kapp)]TJ 64.25 0 TD [(a)-300.3(B)-297.8(\(NF-kB\),)]TJ -64.25 -1.3606 TD 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[(level)-352.4(at)-347.1(the)-350.3(start)-349.5(of)-348.8(treatment,)-353.8(revealing)-356.6(an)-346.8(ongoing)-352.4(subclinical)]TJ 0 -1.2055 TD 0.0085 Tc (in)Tj /F12 1 Tf 0.8176 0 TD 0 Tc ()Tj /F11 1 Tf 0.5431 0 TD 0.0085 Tc [(am)8.5(m)-8.6(a)-2.1(tio)-4.7(n)0.5(.)-507.5(M)-1.6(ore)-512.4(r)8.5(e)-11.2(cen)-5.5(tly,)-513.5(Boe)-5.2(t)0.2(ers)-510.7(e)0.8(t)-513(a)8.5(l)-8.7(.)-507.5(\()]TJ 0 0 0 0.7 k 18.1596 0 TD 0.0103 Tc (30)Tj 0 0 0 1 k 0.9787 0 TD 0.0078 Tc [(\))-508.5(r)-4.2(ev)-5.6(eale)-5.9(d)-510.6(a)]TJ -20.4989 -1.2114 TD 0 Tc (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-315.1(association)-321.5(between)-318.6(higher)-316.4(SAA)-312.3(levels)-316.6(\(>3)-319.9(ug/ml\))-314.7(at)]TJ -2.4169 -1.2114 TD 0.0263 Tc [(dise)-5.3(ase)-524.5(o)-4.8(nse)-5.3(t)-525.1(and)-527.9(a)-2.2(chie)-5.3(vement)-531(of)-524.1(sustaine)-5.3(d-DMARD-free)]TJ T* 0 Tc [(remission)-469.4(\(de)]TJ /F12 1 Tf 5.6335 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ned)-468.5(as)-470.1(the)-463.7(absence)-472.7(of)-468.2(synovitis)-467.5(that)-468.9(sustained)]TJ -6.1646 -1.2114 TD [(after)-338.4(discontinuation)-342.2(of)-336.9(all)-334.1(DMARD)-342.4(therapy)-337.8(to)-337.8(at)-335.2(least)-337.6(1)-332.6(year\))]TJ T* 0.023 Tc [(sugge)-2.6(st)-3.2(in)-2.9(g)-527.5(a)-524.7(pre)-2.6(d)-6(ic)-2.6(t)-3.2(i)-3.4(ve)-527.8(value)-527.8(o)-2.2(f)-527.4(S)1.7(AA)-6.1(.)-522.9(M)-5.1(igi)-3.4(t)2.7(a)-530.6(e)3.4(t)-528.4(a)0.5(l.)-528.8(\()]TJ 0 0 0 0.7 k 23.805 0 TD 0.0282 Tc [(13)5.9(0)]TJ 0 0 0 1 k 1.5098 0 TD 0 Tc (\))Tj -25.3148 -1.2114 TD [(demonstrated)-360.3(that)-349.6(Janus)-352.3(kinase)-357.5(inhibition)-353.7(down-regulates)-361.9(IL-6)]TJ 0 -1.2055 TD 0.0228 Tc [(induced)-525.4(SAA)-525.5(e)3.2(xpression)-522.3(in)-522.3(rheumatoid)-525.4(synovium.)-523.1(I)-2.3(n)-522.3(t)2.5(he)]TJ 0 -1.2114 TD 0.0294 Tc [(subsequent)-533.9(stu)-5.6(d)0.4(y)-533.1(\()]TJ 0 0 0 0.7 k 8.5039 0 TD 0.0283 Tc (31)Tj 0 0 0 1 k 1.0205 0 TD 0.0298 Tc [(\))-528.3(t)-2.4(hey)-532.7(v)-1.5(alidated)-530.3(SAA)-530.4(a)-4.6(s)-531.2(a)-529.8(sensitive)]TJ -9.5244 -1.2114 TD 0 Tc [(biomarker)-333.8(of)-330.9(response)-340.3(to)-331.9(tofacitinib)-335.1(\(Janus)-331.5(kinase)-339.6(inhibitor\))-334.3(in)]TJ T* [(patients)-283.5(with)-276.9(active)-277.1(RA.)-283.2(Tofacitinib)-279.8(reduced)-283.3(both)-273.6(IL-6)-278.3(and)-280.4(SAA)]TJ T* [(serum)-263.2(levels.)-265.7(In)-265.8(patients)-265.5(who)-261.3(experienced)-271.8(a)-261.2(post-treatment)-268.4(SAA)]TJ T* 0.0191 Tc [(no)5.9(rmal)6.5(izat)4.8(ion)5.1(,)-520.8(t)4.8(h)1.1(e)-513.8(d)-4(e)5.4(c)-0.5(rease)-513.8(o)]TJ 12.9498 0 TD 0.0174 Tc [(f)-515.1(d)-5.7(isease)-515.5(activity)-521.2(was)-519.7(g)-2(reater)]TJ -12.9498 -1.2055 TD 0 Tc [(compared)-460.9(to)-451.2(those)-459.1(with)-455.9(persistently)-461.8(high)-457.9(levels.)-456.7(This)]TJ /F12 1 Tf 22.8084 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (nding)Tj -23.3395 -1.2114 TD [(sugg)-8.2(ests)-505.4(that)-504.8(SAA)-509.3(may)-501(be)-504.3(used)-507.4(for)-504(mo)-6.9(nitoring)-509.8(respon)-10.3(se)-503(to)]TJ T* [(tofacitinib)-305.3(in)-309(RA)-304.3(patients,)-310.1(although)-302.3(the)-308.6(caution)-306.2(is)-301(needed)-310(when)]TJ T* [(interpreting)-328.5(the)-320.5(results,)-323.1(since)-324.4(only)-315.8(14)-325(patients)-319.3(were)-323.1(included)-328.6(in)]TJ T* 0.0088 Tc [(the)-512.1(s)8.8(t)-11.5(u)8.8(d)-7.5(y)-4.6(,)-507.2(a)-1.8(n)-5.2(d)-509.6(on)-5.2(ly)-511.9(4)-508.8(r)-3.2(ec)-4.9(ei)-5.7(ved)-515.5(t)0.5(ofacit)-5.5(inib)-511.7(as)-510.4(mon)-5.2(o)1.5(therapy.)]TJ T* 0 Tc [(Finally,)-437.7(many)-431.5(researchers)-435.5(investigated)-440(response)-435.8(to)-427.3(anti-TNF)]TJ /F17 1 Tf 25.0343 0 TD (a)Tj /F11 1 Tf -25.0343 -1.2114 TD 0.0618 Tc [(antibodies)-558.9(i)-0.5(n)-566.9(R)1.5(A)-564.1(p)2.9(atients)-564.8(b)0.8(y)-560.3(m)-3.4(onitorin)-5.9(g)-560.3(S)-1.3(AA)-564.1(levels.)]TJ 0 -1.2055 TD 0 Tc [(Visvanathan)-455.4(et)-445.7(al.)-449.7(\()]TJ 0 0 0 0.7 k 8.3189 0 TD (32)Tj 0 0 0 1 k 0.9608 0 TD [(\))-450.7(reported)-447.2(that)-451(the)-445.8(reduction)-451.8(in)-452.2(serum)]TJ -9.2797 -1.2114 TD [(level)-304.7(of)-307.1(SAA)-306.4(at)-305.3(week)-311.5(4)-302.8(after)-308.5(initiation)-311.5(of)-307.1(golimumab)-308.7(therapy)-307.9(in)]TJ T* [(RA)-256.6(patients)-265.5(correlates)-258.9(signi)]TJ /F12 1 Tf 10.9387 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-263.6(with)-259(clinical)-261.3(improvement)-262.3(at)]TJ -11.4698 -1.2114 TD [(week)-389.1(16,)-381.6(suggesting)-394.4(the)-386.1(use)-382.9(of)-384.6(SAA)-389.9(for)-384.7(predicting)-388.9(the)-386.1(clinical)]TJ T* 0.0303 Tc [(response.)-527.5(D)1.4(oyl)5.8(e)-532.4(et)-527(al.)-527.5(\()]TJ 0 0 0 0.7 k 10.7358 0 TD 0.0283 Tc (33)Tj 0 0 0 1 k 1.0145 0 TD 0.0291 Tc [(\))-529(v)-2.2(alid)-5.9(ated)-531(SAA)-531.1(a)0.6(s)-531.9(a)-530.5(potential)]TJ -11.7503 -1.2114 TD 0.0364 Tc [(biomarker)-536.5(f)5.1(or)-536.5(evaluating)-532(response)-538.2(to)-537.8(gol)5.9(i)-2(mumab)-537.8(i)4(n)-538.6(R)-0.1(A)]TJ 0 -1.2055 TD 0.0275 Tc [(pati)-4.9(ent)-4.7(s)-527.5(but)-529.8(d)-1.5(id)-532.6(not)-523.9(f)-3.8(oun)-4.4(d)-526.7(c)-4.1(l)3(i)-4.9(n)1.6(ic)-4.1(ally)-529(relevant)-529.8(corre)-4.1(l)3(at)-4.7(ion)]TJ 0 -1.2114 TD 0 Tc [(between)-342.4(baseline)-342.9(SAA)-342.2(levels)-346.5(and)-340(clinical)-344.8(improvement)-345.9(at)-341.1(week)]TJ T* [(24)-444.4(of)-444.3(golimumab)-446(therapy.)-448(Furthermore,)-449.7(the)-445.8(clinical)-446.3(utility)-440.9(of)]TJ T* [(SAA)-360.1(for)-360.8(assessing)-358.7(response)-364.2(to)-361.7(adalimumab)-362(in)-356.7(RA)-358(patients)-367(has)]TJ T* [(been)-382.8(validated)-386.4(by)-378.8(Kobayashi)-382.4(et)-386(al.,)-380.9(Berner)-383.4(Hammer)-385.4(et)-380.1(al.)-384(and)]TJ T* [(Gabay)-402.1(et)-403.9(al.)-401.9(\()]TJ 0 0 0 0.7 k 5.717 0 TD (34)Tj /F13 1 Tf 0 0 0 1 k 0.9548 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5132 0 TD (36)Tj 0 0 0 1 k 0.9548 0 TD [(\),)-405.8(while)-402.3(Nissinen)-405.9(et)-403.9(al.)-401.9(\()]TJ 9.5 0 0 9.5 219.2881 146.948 Tm 0 0 0 0.7 k (37)Tj 0 0 0 1 k 0.9548 0 TD [(\))-403(reported)-405.4(SAA)]TJ -19.2636 -1.2114 TD [(levels)-274.8(to)-266.2(be)-271.6(signi)]TJ /F12 1 Tf 6.5704 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-275.5(correlated)-270(with)-270.9(clinical)-273.2(improvement)-280.2(in)]TJ -7.1015 -1.2055 TD [(RA)-214.8(patients)-217.8(treated)-220.9(with)-211.3(in)]TJ /F12 1 Tf 10.6403 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(iximab.)-213.8(In)-218.1(addition,)-213.6(Gabay)-217.1(et)-218.9(al.)-211(\()]TJ 0 0 0 0.7 k 13.1885 0 TD (36)Tj 0 0 0 1 k 0.9548 0 TD (\))Tj -25.3148 -1.2114 TD 0.0296 Tc [(comp)-5.4(ared)-530.5(ef)64(fects)-525.4(o)-1.5(f)-526.8(a)-4.8(dalimumab)-526.7(a)1.1(nd)-530.5(sarilumabon)-527.4(serum)]TJ T* 0 Tc [(bio)-11.1(mark)-10.6(er)-7.7(s)-507.3(i)0(n)-505.9(a)-505.9(lar)-11.2(ge)-504.5(c)-7.7(oho)-8.7(rt)-509.6(\(n=3)-10.5(07\))-513.2(of)-510(RA)-507.2(pati)-14.7(ents)-12.1(.)-504.1(The)-8.5(y)]TJ T* [(f)-7.4(o)-13.2(un)-19.1(d)-518.4(a)-517.8(si)-14.5(g)-13.4(n)-8(i)]TJ /F12 1 Tf 5.8125 0 TD ()Tj /F11 1 Tf 0.5371 0 TD 0.0094 Tc [(c)-4.3(a)-1.2(nt)-506.2(greater)-509.8(d)-1.7(ec)-4.3(r)9.4(e)-4.3(ase)-505.6(o)-3.8(f)-505.2(S)0(AA)-509.1(at)-506.2(wee)-4.3(k)-504.2(24)-508.2(in)]TJ -6.3496 -1.2114 TD 0.0465 Tc [(responders)-544.3(than)-546.4(non-responders)-544.3(in)-546.4(ad)5.5(alimumab)-545.6(group.)]TJ 27.4512 66.5811 TD 0 Tc [(Although)-356.6(total)-351.4(SAA)-354.1(reduction)-362.2(was)-354.1(greater)-358.1(in)-350.8(sarilumab)-358.7(group,)]TJ 0 -1.2114 TD [(the)-296.6(association)-297.7(between)-294.7(clinical)-297.1(ef)]TJ /F12 1 Tf 13.5585 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cacy)-296(and)-298.3(SAA)-294.4(reduction)-296.6(was)]TJ -14.0896 -1.2114 TD [(not)-375.7(found)-373.1(in)-374.6(this)-375.1(group,)-374(suggesting)-376.5(that)-373.5(a)-374.6(direct)-377.6(ef)62.5(fect)-371.3(of)-372.7(IL-6)]TJ T* [(blockade)-482.3(on)-486.7(SAA)-479.4(production)-492.3(is)-480(independent)-491.3(of)-480.1(its)-482.4(ef)56.5(fect)-478.7(on)]TJ T* [(disease)-326.2(activity.)-332.4(In)-325.5(addition,)-327(this)-327.3(research)-332.3(reported)-327.8(a)-326.9(signi)]TJ /F12 1 Tf 23.429 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (cant)Tj -23.9601 -1.2114 TD [(predictive)-323(value)-312(of)-319(high)-314.7(baseline)-319(SAA)-318.3(levels)-316.6(for)-319(a)-314.9(better)-313.9(clinical)]TJ 0 -1.2055 TD [(response)-304.5(to)-308(sarilumab)-305(than)-301.6(adalimumab.)-311.1(Further)-307(studies)-303.5(with)-306.8(a)]TJ 0 -1.2114 TD 0.0184 Tc [(lo)5.2(nger)-512.8(follo)5.2(w-up)-517.9(are)-520.4(n)-1.6(eeded)-517.9(f)]TJ 13.2482 0 TD [(or)-512.8(validating)-514.2(a)-4.1(n)4.4(d)-517.9(e)-1.2(xpanding)]TJ -13.2482 -1.2114 TD 0 Tc [(these)-304.4(results.)]TJ 1.2651 -1.2114 TD [(Lately,)-509.1(quantitative)-518.5(methods)-511.6(for)-516(measuring)-512.6(dif)62.5(ferent)-516.6(SAA)]TJ -1.2651 -1.2114 TD 0.0265 Tc [(isof)-4.8(orms)-540.5(and)-539.6(p)-2.5(roteo)-4.6(m)3(i)-5.9(c)-536.2(te)-5.1(chniques)-540.5(fo)-4.6(r)-540.5(e)0.9(xplo)-4.6(rin)-5.4(g)-536(c)-5.1(l)2(in)-5.4(ical)]TJ T* 0 Tc [(r)11.9(e)0(l)21.5(e)0(v)14.7(a)13.3(nc)20.1(e)-401.6(o)0(f)-396.6(t)0(h)21.4(e)0(s)22.1(e)-407.5(is)21.3(of)21.2(or)22.6(ms)-393.5(ar)19.2(e)-407.5(b)0(e)20.8(i)0(n)19.2(g)-401.3(de)17(ve)20.6(lo)21.9(p)12.7(e)0(d)17(.)-402.6(Xu)-392.6(et)-398(a)13.3(l)0(.)-391.3(\()]TJ 0 0 0 0.7 k 24.3779 0 TD (38)Tj 0 0 0 1 k 0.9369 0 TD (\))Tj -25.3148 -1.2055 TD [(d)12.7(e)0(v)14.7(e)0(l)21.5(o)0(p)23.4(e)0(d)-341.1(E)13(L)11.8(I)0(S)19.2(A)-345.4(fo)21.2(r)-352.1(S)14.5(AA)19.3(1)-350.5(a)13.3(nd)-335.4(in)19.2(ve)20.6(st)21.5(ig)19.8(at)16.9(ed)-335.1(le)21.5(ve)20.6(ls)-340.8(a)13.3(n)0(d)-335.4(r)0(a)19.2(t)0(i)18.9(o)0(s)-335.5(o)0(f)]TJ 0 -1.2114 TD [(SA)21.1(A1)-415.4(in)-416.4(to)20.2(ta)22.9(l)-424.3(S)0(A)15.2(A)-423(in)-416.4(h)11.8(e)0(a)17.5(l)0(t)20.9(h)11.8(y)-425.2(s)11.9(ub)17.4(je)21.5(ct)19.8(s)-423.7(a)0(n)17.2(d)-422.9(RA)-417.7(p)12.7(a)0(t)16.9(i)0(e)19.6(n)0(t)25.4(s)0(.)-420.6(T)0(h)23.1(e)0(y)]TJ T* [(fo)21.2(un)16.7(d)-279.7(t)0(h)21.4(a)13.3(t)-282.8(b)0(o)21.3(t)0(h)-271(S)0(A)21.1(A)0(1)-272.2(a)13.3(nd)-275.8(t)15.6(o)0(t)20.2(a)0(l)-273.8(S)14.5(AA)-273.1(ar)19.2(e)-282.2(s)11.9(ig)19.8(ni)]TJ /F12 1 Tf 18.2909 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(nt)19.5(ly)-264.7(el)15.5(ev)20.6(a)13.3(t)0(e)19.8(d)-279.7(in)]TJ -18.8101 -1.2114 TD [(RA)-387.8(p)12.7(a)0(t)16.9(i)15.3(en)14.1(t)15.6(s)-399.9(co)20.8(m)12.3(p)0(a)20.1(r)0(e)16.1(d)-393.1(to)-385.6(h)11.8(e)0(a)17.5(l)0(t)20.9(h)11.8(y)-395.4(s)0(u)18.7(b)0(j)21.9(e)0(c)14.4(t)15.5(s,)-390.7(a)13.3(l)0(t)20.9(h)0(o)16.5(u)12.8(gh)-383.6(th)15.4(e)-395.6(S)14.5(AA)19.3(1/)]TJ T* [(SA)21.1(A)-333.5(r)0(a)19.2(t)0(i)18.9(o)-335.5(di)22.1(d)-339.3(n)0(o)20.5(t)-336.5(d)12.7(i)0(f)79.6(f)0(e)20.7(r)-334.2(be)20.8(tw)18.2(ee)20.4(n)-336.3(t)15.6(he)-330.1(tw)24.2(o)-335.5(g)0(r)16.4(o)0(u)23.4(p)0(s)18.7(.)-337(D)12.9(e)-335.9(Se)18.7(ny)-325.8(et)-326.3(a)13.3(l)0(.)]TJ T* (\()Tj 0 0 0 0.7 k 0.3342 0 TD -0.0135 Tc (39)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc [(\))-444.7(u)0(s)18.7(e)0(d)-436.6(S)0(E)21.5(L)0(D)18.7(I)0(-)18.6(T)0(O)22.2(F)-446.8(MS)-437.3(\(s)20.7(ur)18.7(fa)17.8(ce)20.4(-)13.8(e)0(n)14.1(h)11.8(a)13.3(n)0(c)20.1(e)0(d)-436.6(l)0(a)18.6(s)11.9(er)-437.4(de)17(s)11.9(o)0(r)16.6(p)12.7(ti)18.9(on)20.5(/)]TJ -1.2711 -1.2055 TD [(io)20(ni)19.2(za)23.5(ti)18.9(on)-313.7(ti)18.9(m)12.3(e)0(-)18.1(o)0(f)21.2(-)]TJ /F12 1 Tf 7.4596 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ig)19.8(h)11.8(t)-324.6(ma)19.7(s)11.9(s)-328.3(s)11.9(p)0(e)17(c)0(t)19.8(r)11.9(om)23(et)19.8(ry)16.4(\))-325.4(f)0(o)21.2(r)]TJ /F12 1 Tf 11.3564 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(nd)22.6(in)19.2(g)-323.8(p)0(r)18.7(o)0(t)20.2(e)0(i)19.6(n)0(s)]TJ -19.8604 -1.2114 TD [(th)21.4(at)-299.4(a)13.3(r)0(e)-300.1(s)0(i)15.3(g)0(n)20.3(i)]TJ /F12 1 Tf 5.1859 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(ca)23.5(nt)19.5(ly)-300.5(el)21.5(ev)20.6(at)16.9(ed)-299.3(i)15.3(n)-312.4(RA)-298.3(pa)20.1(ti)18.9(en)20.1(ts)21.5(.)-307.2(I)0(n)14.7(t)15.5(er)16.1(es)22.1(ti)18.9(ng)20.3(ly)21.7(,)-307.2(a)0(l)18.6(o)0(n)20.5(g)]TJ -5.711 -1.2114 TD [(wi)-11.9(th)-527.6(SA)-8.7(A)-524.4(o)0(f)-527.9(1)0(1)-8.8(,)0(6)-13.2(8)0(2)-522(D)0(a)-15.6(,)-522(two)-532.1(tr)-8.3(un)-13.2(c)-7.7(a)0(t)-7(e)-7.7(d)-524.3(and)-531(pr)-11.2(o)-7.2(b)-7.3(abl)-12.5(y)-520.7(p)0(o)-12.4(s)0(t)-14.3(-)]TJ T* [(tr)21.5(an)17.2(s)11.9(l)0(a)18.6(t)0(i)24.9(o)0(n)20.5(a)0(l)18.6(l)0(y)-348.3(m)0(o)17(d)12.7(i)]TJ /F12 1 Tf 7.9609 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ed)-353(S)14.5(A)0(A)-350.7(p)0(r)18.7(o)0(t)20.2(e)0(i)19.6(n)0(s)-348.2(w)0(e)18.8(r)11.9(e)-359.8(a)13.3(ls)17.2(o)-359.3(i)0(d)22.1(e)0(n)20.1(t)0(i)]TJ /F12 1 Tf 13.3437 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ed)17(:)-360.9(S)14.5(AA)]TJ -22.3429 -1.2114 TD [(wi)23.9(th)15.4(ou)23.4(t)-324.6(i)0(t)18.9(s)]TJ /F12 1 Tf 4.5832 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(rs)17.8(t)-324.6(N)0(-)18.8(t)0(e)19.8(r)11.9(m)12.3(i)0(n)19.2(a)0(l)-315.6(A)12.7(rg)-317.8(r)11.9(e)0(s)22.1(i)0(d)16.1(u)12.7(e)-324(o)0(f)-319(1)13.5(1,)16.7(5)13.5(2)0(6)-313.1(D)0(a)-314(\()0(S)17.3(A)12.7(A)-327.5(d)12.7(es)16.1(-)]TJ -5.1023 -1.2114 TD [(A)12.7(r)0(g)16.4(\))-247.8(a)13.3(n)0(d)-240(S)0(A)21.1(A)-249.9(tr)21.5(un)16.7(ca)23.5(te)19.8(d)-249.8(a)13.3(t)-247(t)0(h)21.4(e)-252.4(N-)24.8(te)19.8(rm)18.3(in)19.2(a)13.3(l)-251.3(en)20.1(d)-243.9(b)0(y)-241.5(2)-243.1(re)16.1(s)11.9(i)0(d)16.1(u)12.7(es)22.1(,)-247.5(A)0(r)18.6(g)]TJ T* [(and)-501.2(Ser)12.7(,)-504.1(o)0(f)-504(11,4)13.9(39)-504.1(Da)-499(\(SAA)-494.5(des-A)13.6(rg/d)11(es-Se)12.9(r\).)-501.3(Li)-498(et)-505.4(al.)-497.4(\()]TJ 0 0 0 0.7 k 24.3659 0 TD (40)Tj 0 0 0 1 k 0.9489 0 TD (\))Tj -25.3148 -1.2055 TD [(co)20.9(n)]TJ /F12 1 Tf 1.4263 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(rm)18.3(ed)-287.4(th)21.4(e)-300.1(d)12.7(if)79.6(fe)20.7(r)11.9(e)0(n)20.1(t)0(i)18.9(a)0(l)-285.7(e)0(x)18.7(p)0(r)18.7(e)0(s)22.1(s)0(i)21.3(o)0(n)-289.8(o)0(f)-289.2(S)14.5(AA)-291(in)-285.1(th)21.4(e)-300.1(s)11.9(er)16.1(u)12.8(m)-298(of)-289.1(RA)]TJ -1.9455 -1.2114 TD [(p)12.7(a)0(t)16.9(i)0(e)19.6(n)0(t)19.5(s)-322.3(co)20.9(m)12.3(p)0(a)20.1(r)11.9(ed)-317.2(to)-308(he)16(a)13.3(l)0(t)20.9(h)11.8(y)-323.8(c)0(o)20.9(n)0(t)19.5(r)11.9(ol)16(s)-322.3(b)0(y)-307.1(p)0(r)18.7(o)0(t)20.2(e)0(o)20.8(m)12.3(ic)19.6(s.)-313.2(Se)18.7(ok)-312(et)-314.4(a)13.3(l)0(.)]TJ T* (\()Tj 0 0 0 0.7 k 0.4058 0 TD 0.0581 Tc (41)Tj 0 0 0 1 k 1.0742 0 TD 0.0605 Tc [(\))-569.2(u)1.6(sed)-571.3(a)-570.7(nano)5.5(liqui)4.2(d)-571.3(chromatog)5.3(r)0.8(aphy-tandem)-565.7(m)-4.7(ass)]TJ -1.48 -1.2114 TD 0 Tc [(s)11.9(p)0(e)17(c)0(t)19.8(r)11.9(om)23(et)19.8(ry)-371.5(\(L)20.6(C-)19.4(MS)22.2(/M)19.4(S\))-376.6(t)15.5(o)-383.2(id)22.1(en)20.1(ti)18.9(fy)-372.9(ca)23.5(nd)16.7(id)22.1(at)16.9(e)-377.7(b)0(i)20(o)0(m)23(a)0(r)19.2(k)0(e)15.8(r)11.9(s)-382(f)0(o)21.2(r)]TJ T* [(RA)-298.3(pr)18.7(e-)18.1(s)11.9(c)0(r)16.1(e)0(e)20.4(n)0(i)19.2(n)0(g)20.3(.)-307.2(Th)17.1(ey)-295.7(fo)15.2(u)12.7(n)0(d)-299.6(t)0(h)21.4(e)-312.1(co)20.9(nc)20.1(en)20.1(tr)15.5(a)13.3(t)0(i)18.9(o)0(n)-301.7(o)0(f)-301.1(S)14.5(AA)19.3(4)-308.7(i)0(n)-303(t)0(h)21.4(e)]TJ T* [(s)11.9(e)0(r)16.1(u)12.8(m)-190.6(o)0(f)-181.7(c)0(l)21.5(i)0(n)19.2(i)0(c)19.6(a)13.3(ll)16.6(y)-186.5(h)0(e)16(a)13.3(lt)20.9(h)11.8(y)-192.5(in)19.2(di)22.1(vi)19.8(du)19.5(al)18.6(s)-191(w)0(i)18(t)15.6(h)-191.1(h)0(i)21.2(g)0(h)-180.7(r)0(h)17.7(e)0(u)17(m)12.3(a)13.3(t)0(o)20.2(i)0(d)-180.8(f)0(a)17.8(c)0(t)19.8(o)0(r)]TJ 0 -1.2055 TD [(\(R)20.1(F)12.8(\))-259.7(va)23.7(lu)18.1(es)-240.5(si)15.3(gn)20.3(i)]TJ /F12 1 Tf 6.5286 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)23.5(nt)19.5(ly)-246.8(h)11.8(i)0(g)19.8(h)11.8(er)-246.4(co)20.8(m)12.3(p)0(a)20.1(r)0(e)16.1(d)-249.8(to)-242.3(se)16.1(r)11.9(a)-255.3(wi)18(t)15.5(h)-256.7(no)20.5(r)11.9(m)0(a)19.7(l)-257.3(RF)]TJ -7.0478 -1.2114 TD [(va)17.7(lu)24(es)16.1(.)-211.7(F)12.7(ur)18.7(th)21.4(er)16.1(m)12.3(o)0(r)22.6(e)0(,)-207.4(b)0(y)-199.7(u)0(s)18.7(i)0(n)19.2(g)-210.4(EL)18.8(IS)19.2(A)12.6(,)-211.7(th)15.4(ey)-200.2(va)17.7(li)20.7(d)12.8(a)0(t)22.9(e)0(d)-203.8(a)-213.5(si)21.3(gn)14.3(i)]TJ /F12 1 Tf 22.7845 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(ca)23.5(nt)19.5(ly)]TJ -23.3097 -1.2114 TD 0.0237 Tc [(up)6.6(-r)5.8(eg)4.3(u)6.6(l)-0.8(a)7.2(t)3.4(ed)-524.5(SAA)6.5(4)-529.7(i)3.2(n)-527.4(R)5.1(A)-530.6(p)6.6(a)1.2(t)3.4(i)3.2(e)4.1(n)3.7(t)3.4(s)-0.2(.)-528.1(T)5.1(h)5.7(e)-1.9(r)5.8(e)4.1(fo)4.5(r)5.8(e)4.1(,)-528.1(S)2.3(AA)6.5(4)-529.7(m)6.2(ay)]TJ T* 0 Tc [(r)11.9(e)0(p)17(r)11.9(es)16.1(en)20.1(t)-444(a)-446.2(no)20.5(ve)20.6(l)-442.2(p)0(r)18.7(e)0(s)16.1(c)0(r)22.1(e)0(e)20.4(n)0(i)19.2(n)0(g)-433.2(m)0(a)19.7(r)0(k)17.5(e)0(r)-437.4(f)0(o)21.2(r)-447.6(ea)23.5(r)11.9(l)0(y)-437.8(R)0(A)-435.6(d)0(e)17(t)15.5(ec)14.4(t)15.6(i)0(o)20(n)0(.)]TJ T* [(Re)15.5(ma)13.7(rk)11.6(ab)12(ly)15.7(,)-492.2(SAA)15.9(4)-493.7(w)0(a)15.9(s)-495.3(fou)16(nd)-490.6(to)-487(be)-486.4(su)12.7(pe)11(ri)15.3(or)-490.7(to)-487(CR)16.8(P)-500.2(a)0(s)-488(R)0(A)]TJ T* [(bi)20(om)23(ar)19.2(k)11.6(e)0(r)16.1(,)-450.4(an)17.2(d)-452.7(t)0(h)21.4(e)-455.3(co)20.9(mb)17(in)19.2(a)13.3(t)0(i)18.9(o)0(n)-444.9(o)0(f)-444.3(S)14.5(AA)19.3(4)-452(a)0(n)17.2(d)-452.7(CR)16.8(P)-452.5(h)11.8(ad)-445.4(ev)20.6(en)]TJ T* [(h)11.8(i)0(g)19.8(h)11.8(er)-383.7(p)12.8(r)0(e)16.1(-)13.8(sc)16.1(r)11.9(e)0(e)20.4(n)0(i)19.2(n)0(g)-379.5(e)0(f)]TJ /F12 1 Tf 9.226 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(cy)20.6(.)-390.7(N)0(y)21.4(s)-393.9(et)-380.1(al)18.6(.)-390.7(\()]TJ 0 0 0 0.7 k 6.9404 0 TD -0.0135 Tc (42)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc [(\))-391(i)0(n)19.2(v)0(e)20.6(s)11.9(ti)18.9(ga)23.7(te)19.8(d)-393.1(S)0(A)21.1(A)0(1)]TJ -17.6225 -1.2055 TD [(a)13.3(n)0(d)-198.2(S)0(A)21.1(A)0(2)-194.6(i)0(s)15.3(o)0(f)21.2(o)0(r)22.6(m)0(s)-196.6(a)0(n)17.2(d)-202.1(th)21.4(ei)19.6(r)-208.9(a)13.3(ll)16.6(el)21.5(ic)-195.3(va)23.7(ri)15.3(a)13.3(n)0(t)19.5(s)-208.9(i)15.3(n)-210.9(p)12.7(a)0(t)22.9(i)0(e)19.6(n)0(t)19.5(s)-208.9(w)14.6(i)0(t)18.9(h)-209(ea)23.5(rl)17.2(y-)]TJ 0 -1.2114 TD [(on)20.5(s)11.9(e)0(t)19.8(,)-354.9(w)14.6(e)0(a)17.5(k)11.6(/m)18(od)23.4(er)16.1(a)13.3(t)0(e)-344.2(a)13.3(nd)-341.4(se)16.1(ve)20.6(r)11.9(e)-353.8(RA)23.9(,)-354.9(A)12.7(S,)-340.4(SL)20.3(E,)-341.9(OA)-346.4(a)13.3(n)0(d)-341.4(h)11.8(ea)17.5(lt)20.9(h)11.8(y)]TJ T* [(co)20.9(nt)19.5(r)11.9(o)0(l)21.9(s)0(.)-205.7(T)0(h)23.1(e)0(y)-206.1(f)0(o)21.2(u)0(n)16.7(d)-208.1(SA)15.2(A)12.7(2)-213.2(le)21.5(ve)20.6(ls)-203.6(s)11.9(i)0(g)19.8(n)0(i)]TJ /F12 1 Tf 14.9848 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(nt)19.5(ly)-199.1(hi)15.2(gh)22.2(er)-204.7(in)-201.6(a)13.3(l)0(l)-204.2(t)0(h)21.4(e)-216.6(RA)]TJ -15.504 -1.2114 TD [(p)12.7(a)0(t)16.9(i)0(e)19.6(n)0(t)19.5(s)-334.2(co)20.8(m)12.3(p)0(a)14.1(r)11.9(ed)-323.2(to)-325.9(co)20.8(nt)19.5(ro)16.6(ls)-322.9(an)17.2(d)-333.4(o)0(t)20.2(h)11.8(er)-330(p)12.7(a)0(t)16.9(h)11.8(ol)21.9(og)21.1(ie)19.6(s)-340.2(\()14.8(SL)20.3(E;)-330(OA)23.6(\),)]TJ T* [(wh)20.4(il)20.6(e)-395.6(S)0(A)21.1(A)0(1)]TJ /F17 1 Tf 4.7682 0 TD (b)Tj /F11 1 Tf 0.9369 0 TD [(le)21.5(ve)14.7(ls)-382.6(we)18.8(r)11.9(e)-395.6(in)19.2(cr)16.1(ea)23.5(se)16.1(d)-393.1(o)0(n)20.5(l)0(y)-384.1(i)0(n)-386.6(e)0(a)17.5(r)11.9(ly)21.7(-o)18.5(ns)21.8(et)-386(RA)-387.9(an)17.2(d)]TJ -5.7051 -1.2114 TD [(SA)21.1(A1)]TJ /F17 1 Tf 2.2796 0 TD (a)Tj /F11 1 Tf 0.8713 0 TD [(in)-237.4(s)11.9(e)0(v)20.6(e)0(r)16.1(e)-246.4(RA)18(.)-241.5(T)0(h)17.1(e)-246.4(we)18.8(ig)19.8(h)11.8(t)0(s)-235.1(o)0(f)-235.4(S)0(A)21.1(A)0(1)]TJ /F17 1 Tf 13.7017 0 TD (a)Tj /F11 1 Tf 0.8713 0 TD [(an)17.2(d)-243.9(S)0(A)15.2(A)12.7(1)]TJ /F17 1 Tf 4.0103 0 TD (b)Tj /F11 1 Tf 0.7877 0 TD [(le)21.5(ve)20.6(ls)-233.4(in)]TJ -22.5219 -1.2055 TD [(th)21.4(e)-407.5(t)0(o)20.2(t)15.5(al)-399.1(SA)21.1(A)-405.1(r)11.9(es)16.1(p)12.8(o)0(n)20.5(s)0(e)-395.6(w)0(e)18.8(r)11.9(e)-407.5(d)0(i)16.1(f)76.2(fe)20.7(re)16.1(nt)-392.3(ac)17.5(co)20.8(r)11.9(d)0(i)16.1(n)0(g)-391.5(t)0(o)-397.5(t)0(h)21.4(e)-407.5(s)11.9(t)0(u)22.3(d)0(i)16.1(e)0(d)]TJ 0 -1.2114 TD [(p)12.7(a)0(t)16.9(h)11.8(ol)21.9(og)21.1(ie)19.6(s)-393.9(a)0(n)17.2(d)-393.1(RA)-381.9(se)16.1(ve)20.6(r)11.9(i)0(t)18.9(y)0(.)-386.2(I)0(n)-379.2(p)0(a)20.1(r)0(t)15.5(i)15.3(cu)17(la)18.6(r)11.9(,)-396.7(S)14.5(A)0(A)19.3(1)]TJ /F17 1 Tf 19.8783 0 TD (a)Tj /F11 1 Tf 1.0145 0 TD [(ma)19.7(de)-388.8(u)12.8(p)-393.1(to)]TJ -20.8928 -1.2114 TD [(8)13.5(0)0(%)-185.3(o)0(f)-181.7(t)15.6(ot)20.2(al)-184.3(SA)21.1(A)-190.2(i)0(n)-183.7(R)0(A)-179(w)0(h)20.4(i)0(l)20.7(e)-192.7(SA)21.1(A1)]TJ /F17 1 Tf 13.833 0 TD (b)Tj /F11 1 Tf 0.734 0 TD 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0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT /F6 1 Tf 6.9999 0 0 6.9999 45.3543 744.2644 Tm 0 Tc (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -17.1054 0 TD (14)Tj ET endstream endobj 341 0 obj<> endobj 342 0 obj<> endobj 343 0 obj<> endobj 344 0 obj<> endobj 345 0 obj<> endobj 346 0 obj<> endobj 347 0 obj<> endobj 348 0 obj<> endobj 349 0 obj<> endobj 350 0 obj<> endobj 351 0 obj<> endobj 352 0 obj<> endobj 353 0 obj<> endobj 354 0 obj<> endobj 355 0 obj<> endobj 356 0 obj<> endobj 357 0 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[(\))-223.9(discerned)]TJ -21.2687 -1.2114 TD [(SAA)-306.4(as)-303(a)-303(more)-301(sensitive)-307(marker)-310.7(than)-301.6(CRP)-304.4(or)-299.7(ESR)-307.4(for)-301.1(assessing)]TJ T* [(JIA)-287.2(disease)-284.4(activity)-287.8(de)]TJ /F12 1 Tf 8.8083 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ed)-281.4(by)-283.3(the)-284.7(presence)-288.7(and)-286.3(number)-284.4(of)-283.2(active)]TJ -9.3394 -1.2114 TD [(joints)-295.4(assessed)-299.8(by)-295.2(clinical)-297.1(and)-292.3(ultrasonographic)-301.7(examination.)-298.3(In)]TJ T* [(addition,)-285.2(SAA)-276.5(was)-282.5(elevated)-282.1(in)-279.1(18%)-279.2(of)-277.2(patients)-283.5(with)-282.9(normal)-276.8(ESR)]TJ T* [(and)-357.9(28%)-350.8(of)-360.8(patients)-355.1(with)-354.5(normal)-360.3(CRP)-352.2(\()]TJ 0 0 0 0.7 k 16.4827 0 TD (47)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-352.1(This)-355.5(suggests)-358.5(that)]TJ -17.4435 -1.2114 TD [(SA)-8.7(A)-506.5(sho)-7.4(uld)-512.2(be)-510.3(used)-513.4(as)-511.9(a)-505.9(mark)-10.6(er)-509(of)-510(di)-7.7(seas)-12.4(e)-503(act)-8.7(iv)-10.1(ity)-507.7(in)-511.9(JI)-7.4(A)]TJ 0 -1.2055 TD [(patients,)-304.2(especially)-306.8(in)-297.1(terms)-302.1(of)-301.1(low)-303.6(disease)-302.3(activity.)]TJ 1.2651 -1.2114 TD [(Miyamae)-263.5(et)-260.7(al.)-264.7(\()]TJ 0 0 0 0.7 k 6.463 0 TD (48)Tj 0 0 0 1 k 0.9548 0 TD [(\))-265.7(explored)-263.9(dif)56.5(ferentially)-264(expressed)-269.7(proteins)]TJ -8.6829 -1.2114 TD [(in)-464.1(systemic)-469.1(JIA)-466.2(patients.)-471.3(Paired)-466.6(sera)-465.9(from)-467.8(each)-467.7(patient)-468.4(were)]TJ T* [(analyzed)-350.3(prior)-349.2(to)-343.8(and)-346(after)-350.3(the)-344.4(treatment)-351(with)-348.5(conventional)-346.2(or)]TJ T* [(biologicDMARDs,)-214.9(using)-214.2(the)-207.1(SELDI-TOF)-216.6(MS)-204.6(proteomic)-218.7(analysis.)]TJ T* [(Despite)-328.9(the)-326.5(small)-327.8(number)-332.1(of)-325(patients)-331.2(\(n=23\),)-331.1(highly)-328.7(signi)]TJ /F12 1 Tf 23.429 0 TD ()Tj /F11 1 Tf 0.5371 0 TD (cant)Tj -23.9661 -1.2055 TD [(and)-471.3(consistent)-469.8(changes)-471.3(were)-466.3(observed,)-469.1(with)-467.9(SAA)-473.5(\(11.6)-466.7(kDa\))]TJ 0 -1.2114 TD [(showing)-315.3(the)-314.5(biggest)-309.4(decrease)-321.1(in)-309(expression)-316.5(upon)-318(the)-314.5(treatment.)]TJ T* [(In)-504.5(additi)-10.5(on,)-507.4(respon)-10.3(ders)-508.2(and)-507.1(non-res)-11.3(ponde)-9.4(rs)-501.3(to)-504.9(conve)-8.3(ntiona)-9(l)]TJ T* [(therapy)-361.6(had)-362(signi)]TJ /F12 1 Tf 7.1254 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-362.8(dif)62.5(ferences)-362.6(in)-362.7(baseline)-360.8(SAA)-360.1(expression,)]TJ -7.6565 -1.2114 TD 0.0199 Tc [(sugge)-5.7(sting)-518.7(c)-5.7(linical)-517.8(u)-3.2(tility)-518.7(of)-524.6(SAA)-522.4(f)0.6(or)-523.2(both)-517.3(p)-3.2(redictin)-6(g)-518.7(a)3.4(n)-6(d)]TJ T* 0.0318 Tc [(monitori)5.4(ng)-536.6(response)-530.9(to)-530.4(the)-5.7(r)1.9(apy)-530.7(i)-0.6(n)-531.2(J)1.7(IA)-534.4(patients.)-532(A)2.7(rticles)]TJ 0 -1.2055 TD 0 Tc [(concerning)-446.5(utility)-446.8(of)-438.3(SAA)-443.6(in)-446.2(JIA)-442.3(patients)-444.6(are)-442(summarized)-449.9(in)]TJ /F14 1 Tf 0 0 0 rg 0 -1.2114 TD [(Table)-304.8(2)]TJ /F11 1 Tf 0 0 0 1 k 3.1211 0 TD (.)Tj /F1 1 Tf 11.9999 0 0 11.9999 45.3543 120.359 Tm [(SAA)-301.8(IN)-302.3(ANKYLOSING)-305.6(SPONDYLITIS)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 100.3464 Tm [(Many)-304.8(studies)-309.5(have)-306.4(shown)-311.2(that)-301.9(SAA)-306.4(can)-306.8(be)-307.4(used)-310.5(as)-303(a)-309(marker)-304.7(of)]TJ 0 -1.2114 TD [(disease)-236.7(activity)-234.1(and)-238.6(response)-232.9(to)-236.4(therapy)-236.3(in)-231.4(AS)-235.5(patients)-235.7(\()]TJ /F14 1 Tf 0 0 0 rg 22.0445 0 TD [(Table)-233.2(3)]TJ /F11 1 Tf 0 0 0 1 k 3.0554 0 TD (\).)Tj -25.1 -1.2114 TD [(Lange)-254.7(et)-248.8(al.)-252.7(\()]TJ 0 0 0 0.7 k 5.1083 0 TD (49)Tj 0 0 0 1 k 0.9548 0 TD [(\))-253.8(evaluated)-254.3(SAA)-252.7(as)-249.3(a)-249.3(marker)-257(of)-247.4(disease)-254.6(activity)-257.9(in)]TJ 21.3881 66.6468 TD [(AS)-444.3(and)-447.5(found)-444.7(a)-440.2(signi)]TJ /F12 1 Tf 9.1245 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-446.4(correlation)-448(with)-444(Bath)-444.6(Ankylosing)]TJ -9.6557 -1.2114 TD [(Spondylitis)-468.4(Disease)-469.3(Activity)-467.4(Index)-467.1(\(BASDAI\),)-466.7(the)-469.7(established)]TJ T* [(disease)-391.8(activity)-389.2(score.)-389.6(Moreover,)-390.6(Jung)-390.9(et)-386(al.)-390(\()]TJ 0 0 0 0.7 k 18.6071 0 TD (50)Tj 0 0 0 1 k 0.9548 0 TD [(\))-391(reported)-387.5(that)]TJ -19.562 -1.2114 TD 0.5364 Tc [(S)521(A)513.2(Ai)521.9(ss)518.5(u)519.3(p)513.3(e)522.7(r)518.5(i)515.9(o)517.2(rt)522.1(oC)518.1(R)517.8(P)0.4(a)519.9(n)516.4(dE)519.5(S)521(R)-1.4(i)515.9(n)3.2(t)516.1(h)518.4(ed)519.3(e)516.8(t)516.1(e)516.8(c)522.7(t)516.1(i)515.9(o)523.2(n)-2.7(o)517.2(f)3.9(A)519.2(S)]TJ T* 0 Tc (in)Tj /F12 1 Tf 0.7997 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-449.2(activity.)-445.7(SAA)-443.6(and)-447.5(BASDAI)-439.7(score)-446.4(were)-448.4(elevated)]TJ -1.3308 -1.2114 TD [(and)-346(positively)-353.6(correlated)-347.5(even)-353.2(in)-344.8(AS)-348.9(patients)-349.1(with)-348.5(normal)-348.4(ESR)]TJ 0 -1.2055 TD [(\(42%)-228.7(of)-229.5(all)-232.7(patients\))-232.9(and)-232.6(CRP)-232.8(levels)-233.1(\(24%)-228.7(of)-229.5(all)-232.7(patients)-229.7(included)]TJ 0 -1.2114 TD [(in)-303(the)-296.6(study\).)]TJ 1.2651 -1.2114 TD 0.0222 Tc [(De)-522.6(Vri)-4.2(e)2.6(s)-526.9(e)2.6(t)-523.2(a)-0.3(l.)-523.7(in)-3.7(ve)-3.4(stigate)-3.4(d)-526(the)-522.6(u)-0.9(sefulne)-3.4(s)-1.7(s)-520.9(o)-3(f)-522.3(S)0.8(AA)-526.1(for)]TJ -1.2651 -1.2114 TD 0.015 Tc [(pre)-4.6(d)-2.1(ict)-5.3(i)0.5(ng)-517.6(and)-521.3(m)3.5(onit)-5.3(oring)-517.6(r)-2.9(esponse)-517.9(t)0.7(o)-517.4(a)-1.5(nti)-5.5(-)-1(TNF)]TJ /F17 1 Tf 21.3821 0 TD 0 Tc (a)Tj /F11 1 Tf 1.1518 0 TD 0.0189 Tc [(th)6.8(er)6.9(apy)]TJ -22.5339 -1.2114 TD 0 Tc (\(in)Tj /F12 1 Tf 1.1458 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(iximab)-330.4(or)-329.5(etanercept\))-337(in)-332.9(AS)-331(patients)-331.2(\()]TJ 0 0 0 0.7 k 15.504 0 TD (51)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-328.2(They)-332.3(found)-331.4(that)]TJ -18.1417 -1.2114 TD [(normal)-324.5(baseline)-325(levels)-328.6(of)-325(both)-321.3(CRP)-328.3(and)-322.1(SAA)-324.3(were)-329.1(signi)]TJ /F12 1 Tf 22.7248 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (cantly)Tj -23.256 -1.2055 TD [(associated)-268.8(with)-259(nonresponse)-274.1(to)-260.2(therapy,)-269(while)-259(elevated)-270.1(baselines)]TJ 0 -1.2114 TD [(of)-259.3(each)-264.8(of)-265.3(these)-262.6(acute)-266.2(phase)-262.3(proteins)-265.9(had)-266.5(a)-261.2(high)-260.9(predictive)-269.3(value)]TJ T* [(for)-456.3(response.)-456.5(The)-456.1(combination)-457.1(of)-456.2(elevated)-455.1(baseline)-456.3(CRP)-459.6(and)]TJ T* [(SAA)-240.7(levels)-245(was)-240.7(the)-242.9(strongest)-244.1(predictor)-246.8(of)-241.4(response)-250.8(to)-236.4(anti-TNF)]TJ /F17 1 Tf 25.0343 0 TD (a)Tj /F11 1 Tf -25.0343 -1.2114 TD [(therapy,)-215.3(suggesting)-209.4(these)-214.8(baseline)-211.6(values)-210.6(should)-209.3(be)-211.9(added)-212.8(to)-206.5(anti-)]TJ T* (TNF)Tj /F17 1 Tf 1.8738 0 TD (a)Tj /F11 1 Tf 1.104 0 TD [(response)-477.5(criteria)-481.1(in)-476.1(order)-479.7(to)-475.1(facilitate)-484.1(selection)-479.6(of)-474.1(AS)]TJ -2.9779 -1.2055 TD [(patients)-450.6(who)-446.3(are)-442(likely)-449.1(to)-445.2(respond)-451.1(to)-445.2(this)-446.7(kind)-445.8(of)-444.3(treatment.)]TJ 0 -1.2114 TD [(Interestingly,)-488.1(a)-476(secondary)-483.6(increase)-486(of)-480.1(SAA)-485.4(levels)-477.8(after)-481.6(initial)]TJ T* [(normalization)-258.2(was)-252.6(associated)-256.9(with)-253(developing)-256.1(antibodies)-256.4(against)]TJ T* (in)Tj /F12 1 Tf 0.7997 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(iximab.)-309.3(Therefore,)-310(monitoring)-307.8(SAA)-306.4(levels)-304.7(might)-304.6(be)-307.4(used)-304.5(for)]TJ -1.3308 -1.2114 TD [(detecting)-230.1(anti-drug)-230.4(antibodies)-226.6(even)-227.8(before)-228.3(the)-225(loss)-228.8(of)-223.5(response)-232.9(to)]TJ T* [(adalimumab)-391.9(and)-393.7(clinical)-392.5(deterioration.)-394.6(This)-391.3(intriguing)]TJ /F12 1 Tf 22.8084 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (nding)Tj -23.3395 -1.2114 TD [(was)-342.1(recently)-352(veri)]TJ /F12 1 Tf 6.833 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ed)-347(in)-344.8(a)-344.8(large)-348.7(cohort)-341(of)-348.8(IBD)-342.2(patients)-349.1(\(n=805\))]TJ -7.3641 -1.2055 TD [(receiving)-248.2(adalimumab)-248.7(by)-247.5(Rubin)-250.5(et)-242.8(al.)-246.8(\()]TJ 0 0 0 0.7 k 15.4204 0 TD (189)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-244.6(SAA)-246.7(concentrations)]TJ -16.8586 -1.2114 TD [(were)-466.3(signi)]TJ /F12 1 Tf 4.2251 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-472.4(decreased)-469.5(after)-469.7(introducing)-468.1(adalimumab)-475.4(to)]TJ -4.7562 -1.2114 TD [(t)-8.3(h)0(e)-7.8(r)-12(ap)-9.8(y)-7.5(.)-516(Af)-12.6(te)-10.1(r)-513.2(i)-8.5(n)-8(i)0(t)-10.9(i)-8.5(al)-518.5(no)-9.3(rm)-17.5(al)-11.2(i)-8.5(z)0(a)-12.3(t)0(i)-10.9(o)-7.3(n)-8(,)-510.1(S)-9.4(A)0(A)-517.8(l)-6.6(e)-7.7(v)-7.5(el)-8.4(s)-513.2(s)0(i)-14.5(g)-7.5(n)-8(i)]TJ /F12 1 Tf 22.6831 0 TD ()Tj /F11 1 Tf 0.5371 0 TD 0.0079 Tc [(can)7.9(t)-2.5(ly)]TJ -23.2202 -1.2114 TD 0.0567 Tc [(inc)-4.7(r)-3(eased)-557.2(i)0.4(n)-560(p)-2.2(atie)-4.7(nts)-558(w)-0.3(ho)-559.3(de)-4.7(ve)-4.7(lope)-4.7(d)-557.2(a)-1.6(nti)-5.6(-)-1.1(adalimumab)]TJ T* 0 Tc [(antibodies.)-354.7(High)-348.2(titter)-351.6(of)-348.8(these)-346.1(antibodies)-357.9(were)-347(associated)-352.3(with)]TJ T* [(4.8-fold)-304.6(increase)-301(in)-303(the)-302.6(SAA)-300.4(expression.)]TJ 1.2651 -1.2055 TD [(Li)-211.6(et)-218.9(al.)-211(\()]TJ 0 0 0 0.7 k 3.4016 0 TD (52)Tj 0 0 0 1 k 0.9608 0 TD [(\))-212(con)]TJ /F12 1 Tf 2.0171 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rmed)-215.4(SAA)-216.8(as)-213.5(a)-213.5(diagnostic)-220.8(indicator)-219.3(of)-217.5(AS)-211.6(by)]TJ -8.1757 -1.2114 TD [(a)-452.2(proteomic)-451.4(approach)-452.4(\(MALDI-TOF)-459.5(MS\).)-449.2(Rademacher)-455.7(et)-451.7(al.)]TJ T* (\()Tj 0 0 0 0.7 k 0.3461 0 TD (53)Tj 0 0 0 1 k 0.9548 0 TD [(\))-361.2(validated)-362.5(increased)-365.8(SAA)-360.1(levels)-364.4(in)-362.7(AS)-360.8(patients)-361(but)-360.9(did)-365(not)]TJ -1.3009 -1.2114 TD [(found)-307.5(a)-303(signi)]TJ /F12 1 Tf 5.3052 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-303.2(correlation)-304.8(between)-306.6(baseline)-307.1(SAA)-306.4(levels)-304.7(and)]TJ -5.8364 -1.2114 TD 0.0225 Tc [(ra)6(diograph)4.5(ic)-522.3(spinal)-521.2(pr)4.6(ogress)]TJ 12.3948 0 TD 0.0254 Tc [(io)6.2(n)-519.7(a)2.9(f)6.1(t)5.1(er)-517.7(t)5.1(w)4.2(o)-513(y)0(e)5.8(a)2.9(rs)7.5(.)-520.5(H)3.6(o)6.2(w)4.2(ev)6(e)5.8(r)1.5(,)]TJ -12.3948 -1.2114 TD 0.0246 Tc [(basel)6.1(i)-1.8(ne)-520.2(SAA)-523.7(w)-2.6(as)-524.5(me)5(as)6.7(ure)5(d)-523.6(in)-520.5(a)-523.1(c)-1(o)5.4(h)0.6(ort)-520.8(o)-0.6(f)-519.9(p)-4.4(atien)4.6(t)-1.6(s)-518.5(w)-2.6(ith)]TJ T* 0 Tc [(advanced)-354.8(AS)-348.9(\(mean)-351.3(disease)-356(duration)-351.4(was)-354.1(15)-348.9(years\).)-354(Therefore,)]TJ 0 -1.2055 TD 0.0355 Tc [(before)-539.1(reaching)-532.9(th)5.5(e)]TJ /F12 1 Tf 9.3633 0 TD 0 Tc ()Tj /F11 1 Tf 0.561 0 TD 0.0352 Tc [(nal)-532.4(c)-2.3(onclusion,)-534.5(the)-533.5(f)-2(urther)-531.8(stud)-5.8(ies)]TJ -9.9242 -1.2114 TD 0 Tc [(evaluating)-384.8(SAA)-383.9(as)-386.6(a)-380.6(predictor)-384.1(of)-384.6(the)-386.1(radiographic)-387.5(progression)]TJ T* [(in)-303(early-stage)-303.3(AS)-301.1(patients)-301.4(is)-301(needed.)]TJ 1.2651 -1.2114 TD [(Recently,)-259.9(Wu)-260.5(et)-260.7(al.)-258.7(\()]TJ 0 0 0 0.7 k 8.122 0 TD (54)Tj 0 0 0 1 k 0.9608 0 TD [(\))-259.7(discovered)-259.7(7)-261(over-expressed)-266.4(proteins)]TJ -10.3479 -1.2114 TD [(in)-386.6(the)-380.2(sera)-388.3(from)-384.3(AS)-384.7(patients)-390.9(compared)-389.3(to)-379.6(healthy)-387.1(controls)-385.4(by)]TJ T* [(using)-256(an)-257.3(human)-256.2(antibody)-259.5(array.)-258.3(In)-259.9(this)-255.7(study,)-255.7(a)-255.2(protein)-259.9(with)-259(the)]TJ 0 -1.2055 TD 0.018 Tc [(highest)-515.5(d)0.9(if)64.3(ferential)-513.8(e)-1.6(xpressi)]TJ 11.8339 0 TD 0.0173 Tc [(on)-515.9(was)-519.8(S)-4.1(AA1,)-516.6(e)-2.3(ven)-521.8(i)2.8(n)-515.9(p)-5.8(atients)]TJ -11.8339 -1.2114 TD 0.0317 Tc [(receiving)-530.8(adalimumab.)-532.1(M)3.6(oreover,)-526.1(SAA1)-527.7(was)-535.3(s)1.8(igni)]TJ /F12 1 Tf 22.5398 0 TD 0 Tc ()Tj /F11 1 Tf 0.561 0 TD 0.0309 Tc (cantly)Tj -23.1008 -1.2114 TD 0.0265 Tc [(hi)-5.9(ghe)-5.1(r)-528.5(in)-524.6(patie)-5.1(n)0.6(ts)-528.5(with)-528.6(periphe)-5.1(r)2.6(al)-529.1(joint)-530.8(i)0.1(nvolve)-5.1(me)-5.1(nt)-524.9(an)-5.4(d)]TJ T* 0 Tc (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-406.8(decreased)-409.8(after)-404(24-weaks)-404.8(of)-408.5(adalimumab)-403.8(therapy.)]TJ -2.4169 -1.2114 TD [(Liu)-216.7(et)-213(al.)-216.9(\()]TJ 0 0 0 0.7 k 3.9267 0 TD (55)Tj 0 0 0 1 k 0.9548 0 TD [(\))-218(also)-215.4(performed)-219.1(a)-213.5(proteomic)-218.7(analysis)-219(of)-217.5(AS)-211.6(patient)]TJ /F13 1 Tf 20.1945 0 TD ()Tj /F11 1 Tf 0.2208 0 TD (s)Tj -25.2969 -1.2114 TD [(sera)-298.8(and)-298.3(found)-301.5(that)-301.9(the)-296.6(combination)-301.9(of)-301.1(CRP)-298.5(and)-298.3(SAA1)-298.8(has)-303.1(the)]TJ T* [(highest)-384.4(sensitivity)-389.3(and)-381.8(speci)]TJ /F12 1 Tf 11.4818 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(city)-384.1(for)-378.7(AS)-384.7(diagnosis)-389.8(and)-381.8(disease)]TJ -12.0129 -1.2055 TD [(activity.)-314.4(They)-314.4(con)]TJ /F12 1 Tf 7.2209 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rmed)-316.8(that)-313.8(SAA1)-310.7(is)-318.9(more)-313(sensitive)-319(than)-313.5(total)]TJ -7.752 -1.2114 TD [(SAA)-312.3(in)-309(dif)62.5(ferentiating)-317.4(active)-312.9(from)-306.7(stable)-315(AS)-307.1(as)-309(well)-310.7(as)-315(AS)-307.1(from)]TJ T* [(healthy)-399(controls.)-394.2(All)-400.4(participants)-397.3(in)-398.5(this)-393(study)-402.1(were)-394.7(treatment)]TJ T* [(n)-8(a)-10.6(v)-16(e)-515(a)0(n)-12.6(d)-518.4(w)-9.3(i)-8.5(th)-14.4(o)-7.3(u)0(t)-520.7(c)-7.7(o)-7.3(m)-11.5(o)-7.3(r)0(b)-13.2(i)-8.5(d)-11.1(i)-8.5(t)-8.3(i)0(e)-16.3(s)0(,)-522(m)0(a)-16.1(k)0(i)-14.9(n)-8(g)-514.7(t)-8.3(he)-527(re)-13.7(su)-17.1(l)-6.6(t)-8.3(s)-513.2(h)-12.1(i)-8.5(g)-7.5(hl)-12.7(y)]TJ T* [(reliable)-299.7(and)-304.2(worth)-299.5(of)-241.4(further)-303.3(exploration.)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT /F6 1 Tf 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -17.1054 0 TD (15)Tj ET endstream endobj 363 0 obj<> endobj 364 0 obj<> endobj 365 0 obj<> endobj 366 0 obj<> endobj 367 0 obj<> endobj 368 0 obj<> endobj 369 0 obj<> endobj 370 0 obj<> endobj 371 0 obj<> endobj 372 0 obj<> endobj 373 0 obj<> endobj 374 0 obj<> endobj 375 0 obj<> endobj 376 0 obj<> endobj 377 0 obj<> endobj 378 0 obj<> endobj 379 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 380 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 381 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 382 0 obj<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 383 0 obj<>stream /GS1 gs BT /F1 1 Tf 11.9999 0 0 11.9999 45.3543 708.6046 Tm 0 0 0 1 k 0 Tc 0 Tw [(SAA)-301.8(IN)-302.3(DIFFERENT)-301.9(TYPES)]TJ 0 -1.1669 TD [(OF)-300.6(VASCULITIS)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 674.5889 Tm [(As)-351.4(in)-356.7(other)-351.7(IRD,)-355.8(studies)-351.2(have)-354.1(shown)-352.9(that)-355.6(SAA)-354.1(is)-348.7(a)-356.7(potentially)]TJ 0 -1.2055 TD [(good)-343.4(biomarker)-345.7(of)-342.9(diseases)-344.1(activity)-347.5(and)-346(response)-346.3(to)-337.8(therapy)-349.7(in)]TJ 0 -1.2114 TD [(patients)-205.9(with)-205.3(Takayasu)-206.5(arteritis)-201.3(\(TA\))-209.1(and)-202.8(other)-202.5(types)-201.8(of)-205.6(vasculitis)]TJ T* (\()Tj /F14 1 Tf 0 0 0 rg 0.3461 0 TD [(Table)-346.6(4)]TJ /F11 1 Tf 0 0 0 1 k 3.1688 0 TD [(\).)-346.1(Ma)-349(et)-344.2(al.)-348.2(\()]TJ 0 0 0 0.7 k 5.2396 0 TD (56)Tj 0 0 0 1 k 0.9608 0 TD [(\))-343.3(and)-352(Nair)-348.4(et)-344.2(al.)-348.2(\()]TJ 0 0 0 0.7 k 7.3462 0 TD (57)Tj 0 0 0 1 k 0.9608 0 TD [(\))-343.3(found)-349.3(circulating)]TJ -18.0223 -1.2114 TD [(SAA)-246.7(levels)-245(signi)]TJ /F12 1 Tf 6.3675 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(cantly)-239.7(higher)-244.8(in)-243.3(TA)-244.6(patients)-247.6(with)-241.1(active)-247.3(disease)]TJ -6.9046 -1.2114 TD [(compared)-210.3(to)-200.6(those)-208.4(with)-205.3(inactive)-204.2(disease.)-209.6(Nevertheless,)-212.4(SAA)-204.9(levels)]TJ T* [(in)-326.9(the)-332.4(inactive)-329.5(group)-335.4(were)-329.1(still)-328.5(higher)-334.3(than)-325.4(in)-332.9(healthy)-333.4(controls,)]TJ T* 0.0095 Tc [(su)9.5(g)-9.1(g)2(estin)-4.5(g)-505.2(an)-511.7(ongoin)-4.5(g)-505.2(s)-2.5(ubclinic)-4.2(al)-504.4(i)-5(n)]TJ /F12 1 Tf 15.7367 0 TD 0 Tc ()Tj /F11 1 Tf 0.5371 0 TD 0.0096 Tc [(amma)9.6(t)-9.3(i)1.1(on,)-512.4(w)0.3(h)9.6(i)-11(ch)-509.7(was)]TJ -16.2738 -1.2055 TD 0 Tc [(occasionally)-362.9(con)]TJ /F12 1 Tf 6.648 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rmed)-364.6(by)-354.9(a)-362.7(FDG)-358.5(PET-CT)-361.8(\()]TJ /F12 1 Tf 10.9745 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (uorodeoxiglucose)Tj -18.6847 -1.2114 TD [(positron-emission)-452.4(computed)-451.9(tomography\))-450.3(and)-441.5(led)-449.1(to)-445.2(therapy)]TJ T* [(adjustment.)-283.1(In)-277.8(the)-278.7(same)-274.5(manner,)-281.4(no)-277.9(signi)]TJ /F12 1 Tf 16.7631 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-279.3(dif)62.5(ferences)-285(were)]TJ -17.2943 -1.2114 TD [(found)-223.9(for)-223.5(CRP.)-223.7(Furthermore,)-228.9(Nair)-229(et)-218.9(al.)-222.9(\()]TJ 0 0 0 0.7 k 16.244 0 TD (57)Tj 0 0 0 1 k 0.9608 0 TD [(\))-223.9(analyzed)-225(changes)-226.6(in)]TJ -17.2048 -1.2114 TD [(biomarker)-405.4(levels)-406.1(and)-405.7(disease)-403.8(activity)-407.1(as)-398.5(a)-404.4(response)-405.9(to)-403.5(therapy)]TJ T* [(\(m)-8.7(ycop)-9.7(heno)-11.2(lat)-7.6(e)-503(m)0(o)-6.9(feti)-8.1(l,)-510.7(azath)-13.4(iopr)-9(ine)-507.7(o)-7.3(r)-501.3(me)-7.3(tho)-9.7(trexa)-12.2(te\).)-511.3(SA)-8.7(A)]TJ 0 -1.2055 TD 0.0071 Tc [(le)-6.6(ve)-6.6(ls)-512.1(s)-4.9(i)-1.4(gni)]TJ /F12 1 Tf 4.6548 0 TD 0 Tc ()Tj /F11 1 Tf 0.5371 0 TD 0.0137 Tc [(ca)13.7(nt)5.4(l)7.1(y)-507(de)6(cr)13.7(e)-6(a)13.7(se)6(d)-510.6(d)13.7(uri)5.2(n)5.7(g)-507(t)5.4(he)-501.3(fo)6.5(ll)7.1(o)6.5(w)4.4(-up)-504.7(o)0.5(f)-500.9(m)2.2(e)6(a)3.1(n)]TJ -5.1919 -1.2114 TD 0 Tc [(duration)-470.8(of)-468.2(7.5)-465.1(months)-470.9(in)-470.1(treatment)-470.4(responders,)-473.6(while)-467.9(there)]TJ T* [(wer)-11.1(e)-503(n)-8(o)-502.6(s)0(i)-8.6(gni)]TJ /F12 1 Tf 5.8364 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(can)-8.4(t)-509.6(chan)-8.5(g)-7.5(e)0(s)-509(i)0(n)-505.9(n)-8(on-)-7.4(re)-7.7(spon)-14.5(ders)-12.9(.)-504.1(T)-6.6(he)-509.1(re)-7.7(lat)-7.6(ive)]TJ -6.3735 -1.2114 TD [(changes)-346(in)-344.8(SAA)-342.2(values)-347.9(during)-350.7(follow-up)-345.2(re)]TJ /F12 1 Tf 17.6344 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ected)-340.9(the)-344.4(response)]TJ -18.1655 -1.2114 TD [(to)-308(treatment)-315.2(more)-307(accurately)-316.5(than)-307.5(the)-314.5(same)-310.3(changes)-310.2(in)-309(CRP)-310.4(or)]TJ T* [(ESR)-206(values.)-207.5(These)-207.2(results)-212.9(are)-203.3(limited)-211.6(by)-205.7(a)-201.5(small)-208.4(cohort)-203.7(size,)-211.8(hence)]TJ T* [(further)-392.8(studies)-387(with)-390.3(a)-386.5(longer)-389.2(follow-up)-387(and)-393.8(in)-386.6(a)-386.5(larger)-390.5(cohort)]TJ 0 -1.2055 TD [(should)-495.8(ascertain)-497.2(the)-493.6(utility)-500.6(of)-492(monitoring)-498.7(SAA)-491.4(levels)-495.6(in)-500(the)]TJ 0 -1.2114 TD [(management)-306.3(of)-301.1(TA)-298.3(patients.)]TJ 1.2651 -1.2114 TD [(L)11.8(a)13.3(te)19.8(ly)15.7(,)-158(a)0(n)-149.9(i)0(m)21.7(p)0(o)17.4(r)11.9(ta)16.9(nt)-147.6(r)11.9(o)0(l)21.9(e)-162.9(of)-151.9(SA)21.1(A)-160.4(i)0(n)-147.9(t)0(h)21.4(e)-162.9(pa)20.1(th)21.4(og)21.1(en)20.1(es)16.1(is)-145.8(of)-151.9(gi)19.8(an)17.2(t)-157.5(c)0(e)20.4(l)0(l)]TJ -1.2651 -1.2114 TD [(ar)19.2(te)19.8(r)11.9(i)0(t)18.9(i)0(s)-378.6(\()14.8(GC)15.3(A)12.7(\))-385.1(ha)19.1(s)-387.9(b)0(e)20.9(e)0(n)-379.8(r)11.9(ec)20.4(og)21.1(ni)19.2(ze)20.4(d.)-378(Al)18(on)20.5(g)-389.4(w)14.6(it)18.9(h)-388(p)12.8(ro)16.6(a)13.3(n)0(g)20.3(i)0(o)20(g)0(e)20.6(n)0(i)19.2(c)]TJ T* [(properties)-443.8(and)-447.5(the)-445.8(induction)-442.7(of)-450.3(cell)-446.4(growth)-444.3(and)-447.5(angiogene)10.7(sis)]TJ T* [(m)12.3(e)0(d)17(i)0(a)22.7(t)0(e)19.8(d)-255.8(by)-247.5(TL)17.1(R2)24.8(,)-259.4(O)]TJ /F13 1 Tf 8.4741 0 TD ()Tj /F11 1 Tf 0.2089 0 TD [(Ne)21.1(il)-247.9(et)-242.8(al)18.6(.)-253.4(\()]TJ 0 0 0 0.7 k 4.3266 0 TD [(19)21.1(0)]TJ 0 0 0 1 k 1.4084 0 TD 0.2538 Tc [(\)p)253.8(r)272.5(o)253.8(v)274.9(e)253.8(d)8.2(t)253.8(h)275.2(a)253.8(t)8.1(S)253.8(A)269(A)-2.1(i)269.1(s)-2.8(d)253.8(i)269.9(r)265.7(e)253.8(c)274.2(t)253.8(l)274.7(y)]TJ -14.4179 -1.2055 TD 0 Tc [(s)11.9(e)0(c)20.4(r)0(e)16.1(t)0(e)19.8(d)-411(in)-398.5(in)]TJ /F12 1 Tf 5.538 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(am)19.7(ma)19.7(to)20.2(r)11.9(y)-413.3(te)19.8(m)12.3(p)0(o)17.4(r)11.9(al)-399.1(ar)19.2(te)19.8(r)11.9(i)0(e)19.6(s)0(.)-402.7(H)0(o)18.7(c)0(e)20.4(v)0(a)23.7(r)-411.8(et)-398(al)18.6(.)-414.6(\()]TJ 0 0 0 0.7 k 18.3207 0 TD (58)Tj 0 0 0 1 k 0.9369 0 TD (\))Tj -25.3148 -1.2114 TD [(r)11.9(e)0(p)17(o)0(r)22.6(t)0(e)19.8(d)-160.3(a)-159.8(p)0(r)18.7(e)0(d)17(i)15.3(ct)19.8(iv)19.8(e)-162.9(v)0(a)23.7(l)0(u)18.1(e)-162.9(of)-145.9(h)11.8(i)0(g)19.8(h)-161.2(ba)18(s)11.9(e)0(l)21.5(i)0(n)19.2(e)-162.9(S)14.5(A)0(A)-153.7(l)0(e)21.5(v)0(e)20.6(l)0(s)-149.9(\()0(m)21.1(e)0(a)17.5(s)11.9(ur)18.7(ed)-150.1(a)13.3(t)]TJ T* [(di)22.1(ag)17.8(no)20.5(s)11.9(i)0(s)15.3(\))-426.8(fo)21.2(r)-429.7(a)0(n)-418.4(e)0(a)17.5(r)11.9(ly)-419.9(re)16.1(la)24.6(ps)18.7(e)-431.4(i)0(n)-422.4(p)12.7(at)22.9(ie)19.6(nt)19.5(s)-429.7(w)0(i)18(t)0(h)-420.2(G)0(C)21.3(A)-428.9(r)11.9(e)0(c)20.4(e)0(i)19.6(v)0(i)19.8(n)0(g)]TJ T* [(co)14.9(rti)18.9(cos)14.9(te)13.8(ro)16.6(ids)16.1(,)-438.4(i)0(n)13.3(dic)20.4(ati)20.3(ng)-433.2(a)-440.2(c)0(l)15.5(i)0(n)13.3(i)0(c)13.6(a)0(l)-434.9(u)0(t)16.4(i)0(l)14.7(i)0(t)13(y)-437.1(of)-432.4(SAA)-425.7(in)-428.3(an)-436.3(ea)17.5(rly)]TJ T* [(id)16.1(en)14.1(ti)]TJ /F12 1 Tf 2.2498 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(ti)13(on)-421.1(of)-426.4(no)14.6(n-)17.8(r)11.9(e)0(s)16.1(p)0(o)17.4(n)0(d)16.7(e)0(r)16.1(s)-435.7(to)-421.4(co)14.9(rt)15.5(ic)19.6(os)16.6(te)13.8(r)11.9(o)0(i)14(d)-428.9(th)15.4(er)16.1(ap)14.1(y.)-422.1(Th)17.1(e)]TJ -2.769 -1.2114 TD [(cor)14.9(rel)15.5(at)16.9(ion)-429.6(of)-432.4(ba)12(sel)15.5(ine)-430.1(SAA)-425.7(wit)15.6(h)-441.7(rel)15.5(ap)14.1(se)-437.4(wa)15.9(s)-441.6(mor)17(e)-437.4(sig)13.8(ni)]TJ /F12 1 Tf 23.4529 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(ca)11.6(nt)]TJ -23.978 -1.2114 TD [(th)21.4(an)-233.4(th)21.4(at)-233.7(of)-235.4(CR)22.8(P)-243.6(o)0(r)-234(E)0(S)15.5(R)0(.)-230.2(T)0(h)17.1(e)-240.4(re)16.1(p)12.7(o)0(r)22.6(t)0(e)19.8(d)-243.9(co)14.9(r)11.9(r)11.9(e)0(l)21.5(a)0(t)16.9(i)0(o)20(n)0(s)-234.8(a)13.3(r)11.9(e)-246.4(li)20.7(m)12.3(i)0(t)18.9(e)0(d)-233.7(b)0(y)]TJ 0 -1.2055 TD [(a)-231.4(s)0(m)18.3(a)13.3(ll)-222.1(co)20.8(ho)16.5(r)11.9(t)-235.1(s)11.9(i)0(z)19.6(e)-228.5(an)17.2(d)-231.9(p)0(o)17.4(t)0(e)19.8(n)0(t)25.4(i)0(a)16.7(l)-233.4(s)11.9(e)0(l)21.5(e)0(c)20.4(t)0(i)18.9(o)0(n)-224.1(b)0(i)20(a)13.3(s)-232.8(s)11.9(in)19.2(ce)-224.3(th)21.4(e)-234.5(s)11.9(tu)16.4(d)12.8(y)-234.2(w)14.6(a)0(s)]TJ 0 -1.2114 TD [(pe)17(r)11.9(f)0(o)21.2(r)11.9(me)16.6(d)-309.5(a)0(t)-305.3(o)0(n)20.5(e)-312.1(d)12.8(e)0(p)17(a)13.3(rt)21.5(me)16.6(nt)-302.8(in)-303(a)-309(s)11.9(in)19.2(gl)21.7(e)-312.1(c)0(e)14.4(n)0(t)25.4(r)0(e)16.1(.)-313.1(Bu)22.9(rj)17.2(a)-309(e)0(t)-302.5(a)0(l)18.6(.)-313.1(\()]TJ 0 0 0 0.7 k 24.3779 0 TD (59)Tj 0 0 0 1 k 0.9369 0 TD (\))Tj -25.3148 -1.2114 TD [(id)22.1(en)20.1(ti)]TJ /F12 1 Tf 2.2379 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ed)-126.2(SA)21.1(A)-130.6(a)0(s)-124(t)0(h)21.4(e)-133(m)12.3(o)0(s)16.6(t)-127.7(di)16.1(f)76.2(f)0(e)14.8(r)11.9(en)20.1(ti)18.9(a)13.3(l)0(l)22.6(y)-132.8(ex)18.7(pr)18.7(es)22.1(se)16.1(d)-130.5(s)11.9(er)16.1(u)12.8(m)-130.9(bi)20(om)17(a)13.3(r)0(k)17.5(e)0(r)]TJ -2.7571 -1.2114 TD [(be)20.8(tw)18.2(ee)20.4(n)-246.7(p)0(a)20.1(t)0(i)18.9(e)0(n)20.1(t)0(s)-241.1(w)14.6(it)18.9(h)-250.8(G)0(C)21.3(A)-249.9(a)13.3(n)0(d)-240(H)0(C)-243(\()0(8)22.3(3)0(-)21.4(f)0(o)21.2(l)0(d)-238.5(i)0(n)19.2(c)0(r)16.1(e)0(a)23.5(s)0(e)-240.5(i)0(n)-237.4(p)0(a)20.1(t)0(i)18.9(e)0(n)20.1(t)0(s)21.5(\))]TJ T* [(ou)17.4(t)-133.6(o)0(f)-122.1(4)0(8)-128.1(t)0(e)19.8(s)11.9(te)19.8(d)-136.4(l)0(a)18.6(b)0(o)21.3(r)11.9(at)16.9(or)22.6(y)-132.8(p)0(a)20.1(r)0(a)19.2(m)0(e)16.6(t)0(e)19.8(r)11.9(s)-137.3(\()0(i)24.1(n)0(c)14.1(l)0(u)24(d)0(i)16.1(n)0(g)-122.9(C)0(R)22.8(P)-136.2(an)17.2(d)-136.4(E)13(SR)19.8(\).)-131.3(A)12.7(l)0(l)]TJ T* [(pa)20.1(ti)18.9(en)20.1(ts)-175.4(in)19.2(cl)21.5(ud)19.5(ed)-180(in)-177.7(th)21.4(e)-186.7(s)0(t)15.5(u)12.7(dy)-179.7(we)18.8(r)11.9(e)-186.7(in)-177.7(ea)17.5(r)11.9(l)0(y)-181.2(d)12.8(is)21.3(ea)17.5(s)11.9(e)-186.7(st)15.5(a)13.3(g)0(e)20.6(,)-187.8(tr)15.5(ea)23.5(tm)21.9(en)20.1(t)]TJ 0 -1.2055 TD [(na)17.2()15.3(v)0(e)-140.5(a)0(n)17.2(d)-142.4(we)18.8(re)-139(fo)21.2(ll)22.6(ow)19.3(ed)-138.2(up)-141.6(fo)21.2(r)-149.2(a)13.3(t)-151.5(l)0(e)21.5(a)13.3(st)-139.6(1)-147.6(y)0(e)20.6(a)0(r)19.2(.)-146(Ch)17.3(a)13.3(n)0(g)20.3(e)0(s)-139(i)0(n)-135.9(S)0(A)15.2(A)-148.5(le)21.5(ve)20.6(ls)]TJ 0 -1.2114 TD [(we)18.8(r)11.9(e)-204.6(be)20.8(tt)19.2(er)-198.7(co)20.8(r)11.9(r)11.9(e)0(l)15.5(a)13.3(te)19.8(d)-208.1(w)14.6(it)18.9(h)-203(d)0(i)16.1(s)11.9(ea)17.5(s)11.9(e)-204.6(ac)17.5(ti)18.9(vi)19.8(t)15.6(y)-210.4(t)15.6(h)0(a)19.1(n)-205(ch)16(a)13.3(n)0(g)20.3(e)0(s)-198.7(i)0(n)-195.6(C)0(R)22.8(P)-207.8(or)]TJ T* [(E)13(S)0(R)-135.4(l)0(e)15.5(v)0(e)20.6(l)0(s)23.2(.)-146(Co)22.1(ns)21.8(id)16.1(er)22.1(in)19.2(g)-144.7(t)0(h)21.4(e)-145(la)24.6(rg)16.4(e)-145(p)12.8(ro)16.6(p)12.8(o)0(r)22.6(t)0(i)18.9(o)0(n)-134.6(o)0(f)-134(s)11.9(mo)17(k)11.6(e)0(r)22.1(s)-149.2(\()14.8(3)0(8)21.1(%)0(\))18.8(,)-146(ty)20(p)12.7(e)]TJ T* [(II)-378.3(di)16.1(a)13.3(b)0(e)20.8(t)0(e)19.8(s)-393.9(\(1)22.3(4%)17.6(\))-391(a)0(n)17.2(d)-387.1(hy)16.3(p)12.7(e)0(r)16.1(t)15.6(en)20.1(si)15.3(ve)-379.2(pa)20.1(ti)18.9(en)20.1(ts)-378.3(\(5)16.4(3)13.5(%)0(\))-381(i)0(n)-386.6(t)15.6(he)-383.8(s)11.9(t)0(u)16.4(d)12.7(y)]TJ T* [(co)20.8(h)11.8(o)0(r)16.6(t)0(,)-178.2(a)13.3(s)-191(w)14.6(el)15.5(l)-185.6(a)13.3(s)-191(t)0(h)21.4(e)-186.7(fa)17.8(ct)-177.2(th)21.4(at)-180(h)11.8(e)0(a)17.5(l)0(t)20.9(h)11.8(y)-186.5(c)0(o)20.9(n)0(t)19.5(r)11.9(ol)16(s)-185(s)11.9(ig)19.8(ni)]TJ /F12 1 Tf 19.6515 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(nt)19.5(ly)-175.2(di)16.1(f)76.2(f)0(e)20.7(r)0(e)16.1(d)]TJ -20.1707 -1.2114 TD [(in)-219.5(a)13.3(g)0(e)-224.1(\()14.8(me)16.6(d)12.7(i)0(a)16.7(n)-228.8(a)13.3(g)0(e)-218.1(o)0(f)-223.5(7)13.5(4.)16.7(1)-225.2(i)0(n)-219.5(p)12.8(at)16.9(ie)19.6(nt)19.5(s)-226.8(v)0(s)22.3(.)-229.6(50)21.1(.8)-222(in)-219.5(h)11.8(e)0(a)17.5(l)0(t)20.9(h)11.8(y)-228.3(c)0(o)20.9(n)0(t)19.5(r)11.9(ol)21.9(s\))20.7(,)]TJ T* [(fut)-8.9(ure)-460.5(re)-7.7(se)-7.7(arch)-460(sho)-13.4(uld)-458.5(co)-9(rro)-7.3(bor)-8.6(ate)-462.2(the)-457.8(obs)-8.6(er)-7.7(ved)-461.9(cor)-9(rel)-8.4(atio)-10.8(ns.)]TJ 0 -1.2055 TD 0.0419 Tc [(Dart)3.7(eve)4.4(l)-489.9(et)-491.6(al)5.5(.)-492(\()]TJ 0 0 0 0.7 k 7.382 0 TD 0.0462 Tc (60)Tj 0 0 0 1 k 1.0443 0 TD 0.5283 Tc [(\)c)484.8(o)491.2(n)]TJ /F12 1 Tf 2.4527 0 TD 0 Tc ()Tj /F11 1 Tf 0.5729 0 TD 0.0396 Tc [(rmed)-496.7(clin)-4.2(ic)-3.9(al)-492.2(ut)-4.5(ilit)-4.5(y)-487.1(o)-3.5(f)-492.9(S)0.3(AA)-496.8(in)]TJ -11.4519 -1.2114 TD 0 Tc [(di)22.1(st)15.5(i)15.3(n)0(g)20.3(u)0(i)16.1(s)11.9(h)11.8(i)0(n)19.2(g)-288(GC)21.3(A)-291.7(p)12.7(at)16.9(ie)19.6(nt)19.5(s)-286.5(w)0(i)23.9(t)0(h)-283(a)13.3(ct)19.8(iv)19.8(e)-288.2(f)0(r)22.4(o)0(m)-281.4(t)0(h)21.4(o)0(s)22.6(e)-288.2(wi)18(th)-277(in)19.2(a)13.3(c)0(t)19.8(i)0(v)19.8(e)]TJ T* 0.0188 Tc [(dise)5.1(ase)5.1(.)-467.4(Despit)4.5(e)-466.3(t)-1.5(e)5.1(n)-1.2(denc)5.1(y)-466.1(t)-1.5(o)-465.9(h)0.8(i)4.3(g)-0.6(her)-464.6(S)-2.5(AA)-463.9(con)4.8(cen)4.8(trat)4.5(ion)4.8(s)-470.6(i)4.3(n)]TJ T* 0 Tc [(mi)-8.2(cr)-7.7(o)-7.3(bia)-8.5(l)-460.2(inf)-12(ec)-9.4(tio)-12.2(ns)-8.1(,)-456.3(t)0(h)-8.4(e)0(y)-462.8(o)0(b)-8.5(s)0(e)-7.7(r)0(v)-7.5(e)0(d)-460.4(n)-8(o)-454.8(s)0(t)-8.4(a)0(t)-7(i)-8.5(st)-8.3(ica)-8.9(l)-6.6(l)0(y)-461.7(s)0(i)-8.6(g)0(n)-9.5(i)]TJ /F12 1 Tf 23.4171 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(c)-7.7(ant)]TJ -23.9482 -1.2114 TD [(di)22.1(f)70.2(f)0(e)20.7(r)0(e)16.1(n)0(c)20.1(e)-341.9(be)20.8(tw)18.2(ee)20.4(n)-348.2(a)13.3(ct)19.8(iv)19.8(e)-347.9(d)12.8(is)21.3(ea)17.5(s)11.9(e)-347.9(a)13.3(n)0(d)-341.4(i)15.3(nf)14.4(ec)20.4(t)15.6(i)0(o)20(n)0(,)-339.1(s)11.9(im)21.7(il)20.7(ar)19.2(ly)-336.3(to)-337.8(Va)24(n)]TJ T* [(Sl)19.8(ee)20.4(n)-193(e)0(t)-183.1(a)13.3(l.)-182.5(\()]TJ 0 0 0 0.7 k 4.5533 0 TD (61)Tj 0 0 0 1 k 0.9369 0 TD [(\).)-185(In)20.6(tr)21.5(ig)19.8(ui)16.1(ng)20.3(ly)21.7(,)-193.8(S)14.5(AA)-183.6(wa)15.9(s)-191(s)11.9(ig)19.8(ni)]TJ /F12 1 Tf 11.2789 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(nt)19.5(ly)-181.2(co)20.8(r)11.9(r)0(e)16.1(l)0(a)24.6(t)0(e)19.8(d)-196.1(w)14.6(i)0(t)18.9(h)]TJ 10.1629 66.7243 TD [(s)11.9(e)0(r)16.1(u)12.8(m)-136.9(I)0(L)22.6(-)0(6)-121.8(l)0(e)21.5(v)0(e)14.7(l)0(s)-120(o)0(n)20.5(l)0(y)-121.5(i)0(n)-130(G)15.8(CA)-125(bu)17.4(t)-133.6(n)0(o)20.5(t)-133.6(in)-124(in)19.2(fe)20.7(ct)19.8(io)20(n)-133.3(g)0(r)22.3(o)0(u)17.4(p)12.7(,)-134.1(s)0(u)18.7(g)0(g)20.8(e)0(s)16.1(t)15.5(in)19.2(g)]TJ 0 -1.2114 TD [(p)12.7(a)0(t)16.9(h)11.8(op)17.4(h)11.8(y)0(s)22.3(i)0(o)20(l)0(o)21.9(g)0(i)19.8(c)0(a)17.5(l)-424.3(di)16.1(f)76.2(f)0(e)20.7(r)0(e)16.1(n)0(c)20.1(e)0(s)22.1(.)-432.5(Th)23.1(e)-425.4(l)0(a)18.6(t)0(t)19.2(e)0(r)-413.5(g)0(r)16.4(o)0(u)23.4(p)-428.9(al)18.6(s)11.9(o)-431(co)20.9(n)]TJ /F12 1 Tf 23.059 0 TD ()Tj /F11 1 Tf 0.5192 0 TD -0.0143 Tc [(rm)-14.3(ed)]TJ -23.5782 -1.2114 TD 0.0101 Tc [(SAA)-454.7(e)-3.6(xp)10.1(r)-7(e)2.4(ssion)-457.4(at)-457.7(the)-457.1(t)1.8(iss)10.1(u)-7(e)-457.1(l)-2.5(evel)-456(\(tem)10.1(poral)-456(a)-0.5(r)10.1(t)-10.2(er)10.1(y)-468.9(b)2.8(iopsy\),)]TJ T* 0 Tc [(em)22.5(ph)18.6(as)19.2(iz)19.6(in)19.2(g)-228.3(i)0(t)18.9(s)-226.8(im)15.7(p)12.7(o)0(r)22.6(t)0(a)16.9(n)0(t)-219.2(r)11.9(ol)21.9(e)-234.5(i)0(n)-219.5(G)0(C)21.3(A)12.7(.)]TJ 1.2651 -1.2114 TD [(Th)23.1(e)-294.2(c)0(l)21.5(i)0(n)19.2(i)0(c)19.6(a)0(l)-285.7(a)0(p)20.1(p)0(l)18.1(i)0(c)19.6(a)13.3(bi)20(li)20.6(ty)-284.3(of)-289.2(S)14.5(A)0(A)-285(h)0(a)19.1(s)-298.4(a)13.3(l)0(s)17.2(o)-293.7(be)20.9(en)-284.3(in)19.2(ve)20.6(s)11.9(t)0(i)18.9(g)0(a)17.8(t)0(e)19.8(d)-291.6(in)]TJ -1.2651 -1.2114 TD [(Ka)22.9(wa)15.9(s)11.9(a)0(k)18.9(i)-384.5(di)16.1(s)11.9(e)0(a)17.5(s)11.9(e)-383.7(\()0(K)18.4(D)0(\))15.7(.)-384.7(Mi)23.1(ta)16.9(ni)-374.6(et)-380.1(a)13.3(l)0(.)-379.4(\()]TJ 0 0 0 0.7 k 15.5577 0 TD -0.0135 Tc (62)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc [(\))-385.1(r)11.9(ev)20.6(ea)17.5(le)21.5(d)-387.1(a)-386.5(si)15.3(gn)20.3(i)]TJ /F12 1 Tf 6.9822 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)23.5(nt)]TJ -23.9959 -1.2055 TD [(associ)-10.3(ation)-454.5(of)-456.2(elevated)-461.1(SAA)-455.6(concentra)-11.6(tion)-455.8(and)-453.4(persi)-9.5(stence)-457.2(of)]TJ 0 -1.2114 TD [(co)14.9(ro)16.6(na)11.2(ry)-431.2(ar)13.3(te)19.8(ry)-431.2(le)15.5(sio)20(ns)-431.8(\(a)16.1(ne)14.1(ur)12.7(ys)16.4(ms)12.3(,)-438.4(s)0(t)15.5(e)0(n)14.1(osi)20(s)-435.7(o)0(r)-431(o)0(c)14.9(c)0(l)15.5(u)0(s)12.7(i)0(o)14(n)0(\))-428.9(l)0(a)12.6(t)0(e)]TJ T* [(a)13.3(f)0(t)20.1(e)0(r)-336(K)0(D)-329.7(\()0(m)21.1(e)0(a)17.5(n)-342.2(ti)18.9(m)12.3(e)-341.9(af)17.8(te)19.8(r)-340.2(o)0(n)20.5(s)11.9(et)-332.3(wa)15.9(s)-340.2(1)0(0)-331(y)0(e)20.6(a)0(r)19.2(s)11.9(\).)-334.2(Th)17.1(i)15.3(s)-346.1(a)13.3(s)0(s)17.8(o)0(c)20.9(i)0(a)22.7(t)0(i)18.9(o)0(n)]TJ T* [(wa)21.9(s)-382(s)11.9(up)19.5(po)17.4(r)11.9(t)0(e)19.8(d)-381.1(by)-366.8(lo)21.9(gi)19.8(s)11.9(t)0(i)18.9(c)-377.7(re)16.1(gr)22.3(es)16.1(s)11.9(i)0(o)20(n)-378(an)17.2(a)13.3(l)0(y)21.7(s)0(i)21.3(s)-382(\(a)22.1(dj)18.1(us)18.7(ti)18.9(ng)-367.6(fo)21.2(r)-382(a)13.3(ge)20.6(,)]TJ T* [(s)11.9(m)0(o)17(k)11.6(in)19.2(g,)-123.7(BM)23.8(I,)-123.3(bl)21.9(oo)21.3(d)-130.5(p)0(r)18.7(e)0(s)16.1(s)11.9(ur)18.7(e,)-123.9(t)15.5(o)0(t)20.2(a)0(l)-124.6(c)0(h)22(o)0(l)21.9(e)0(s)16.1(t)0(e)19.8(r)11.9(ol)21.9(/)11.7(H)0(D)21(L)-137.4(r)11.9(a)13.3(ti)18.9(o\))-123.8(a)13.3(n)0(d)-126.6(w)14.6(as)]TJ T* [(s)11.9(t)0(r)21.5(o)0(n)20.5(g)0(e)14.7(r)-304.4(fo)21.2(r)-310.3(S)0(A)21.1(A)-309.6(th)21.4(a)13.3(n)-312.4(fo)21.2(r)-304.4(C)0(R)16.8(P)13(.)-307.2(W)0(h)19(e)0(n)-302.2(i)15.3(nt)19.5(er)16.1(p)12.7(r)11.9(et)19.8(in)19.2(g)-311.8(t)15.6(he)-300.2(r)11.9(e)0(s)16.1(u)12.7(lt)20.9(s,)-301.2(a)]TJ 0 -1.2055 TD [(ca)11.6(uti)13.8(on)-433(is)-438.2(ne)14.1(eded)-425.6(sin)13.2(ce)-439.1(th)15.4(e)-443.3(stu)16.3(dy)-436.3(was)-425.7(cro)14.9(ss-)13.8(sec)14.4(tio)17.7(nal)-431(an)11.2(d)-440.8(the)]TJ 0 -1.2114 TD 0.0418 Tc [(n)3.9(u)0.8(mb)4.7(e)4.3(r)-489.3(o)4.7(f)-484.8(pat)3.6(i)3.4(e)4.3(n)-2(t)3.6(s)-483.4(was)-489.3(r)6(el)5.4(at)3.6(i)3.4(v)4.5(el)5.4(y)-484.9(s)0(ma)7.4(ll)5.4(,)-486.2(s)0(o)-484.6(l)5.3(arg)4.5(e)-485.1(co)4.7(ho)4.7(r)6(t)]TJ T* 0.0247 Tc [(co)5.5(rro)5.5(bor)6.8(at)4.4(i)4.2(o)-0.5(n)-472.7(i)4.2(s)-470.6(r)0.8(equir)6.8(e)-0.9(d.)-473.4(Whi)4.2(t)4.4(in)-472.7(e)5.1(t)-473(al.)-467.5(\()]TJ 0 0 0 0.7 k 18.2551 0 TD 0.0223 Tc (63)Tj 0 0 0 1 k 1.0026 0 TD 0.0231 Tc [(\))-475.3(published)-471.4(an)]TJ -19.2576 -1.2114 TD 0 Tc [(in)19.2(tr)21.5(ig)19.8(u)12.7(i)0(n)19.2(g)-365.5(r)11.9(e)0(p)17(o)0(r)22.6(t)-360.4(on)-355.4(a)-362.7(n)0(o)20.5(v)0(e)20.6(l)-364.7(tr)21.5(u)12.7(n)0(c)20.1(a)0(t)16.9(e)0(d)-353(S)0(A)21.1(A)-363.3(fo)21.2(rm)-351.7(in)-356.7(p)12.8(a)0(t)16.9(i)0(e)19.6(n)0(t)25.4(s)-364.1(in)]TJ 9.5 0 0 9.5 306.1417 526.4503 Tm [(Ka)22.9(wa)15.9(s)11.9(a)0(k)18.9(i)-384.5(di)22.1(se)16.1(a)13.3(s)0(e)16.1(.)-384.7(By)-373.3(us)18.7(in)19.2(g)-383.4(a)-386.5(pr)18.7(ot)20.2(eo)20.8(m)12.3(i)0(c)-380.3(a)13.3(pp)19.5(ro)16.6(a)13.3(c)0(h)-377.8(\()0(S)23.3(E)0(L)18.8(D)0(I)17.7(-)13.8(TO)16.2(F)]TJ T* [(MS)22.2(\),)-149.2(th)15.4(e)-156.9(g)0(r)22.3(o)0(u)17.4(p)-160.3(in)19.2(ve)20.6(s)11.9(t)0(i)18.9(g)0(a)23.7(t)0(e)19.8(d)-160.3(di)16.1(f)76.2(f)0(e)20.7(r)0(e)16.1(n)0(c)20.1(e)0(s)-151(i)0(n)-147.9(s)11.9(er)16.1(u)12.7(m)-160.7(p)12.7(r)0(o)16.6(t)0(e)19.8(i)0(n)-147.9(e)0(x)18.7(p)12.7(re)16.1(s)11.9(s)11.9(i)0(o)20(n)]TJ 0 -1.2055 TD [(be)20.9(tw)18.2(ee)20.4(n)-228.8(c)0(h)22(i)0(l)20.7(d)0(r)18.7(e)0(n)-224.6(w)0(i)23.9(t)0(h)-223.3(K)0(D)-222.2(a)13.3(nd)-222(fe)14.8(br)22.6(il)20.6(e)-228.5(c)0(h)16(i)0(l)20.7(d)12.7(re)16.1(n)-228.8(w)0(i)18(t)0(h)-217.3(a)0(t)-221.8(l)0(e)21.5(a)0(s)19.2(t)-235.1(3)-231.2(d)12.8(ay)17.8(-)]TJ 0 -1.2114 TD [(lo)21.9(ng)-206.5(fe)20.7(ve)20.6(r)-214.9(a)0(n)17.2(d)-214(at)-203.9(le)21.5(as)19.2(t)-217.2(o)0(n)20.5(e)-216.6(of)-199.6(th)15.4(e)-210.6(c)0(l)15.5(i)15.3(ni)19.2(ca)17.5(l)-215.5(c)0(r)22.1(i)0(t)18.9(e)0(r)22.1(i)0(a)-204.1(f)0(o)15.2(r)-214.9(KD)22.4(.)-217.6(O)0(n)20.8(e)-216.6(m)12.3(a)0(s)19.2(s)]TJ T* [(s)11.9(p)0(e)17(c)0(t)19.8(r)11.9(om)23(et)19.8(ry)-234.3(pe)17(a)13.3(k)-245(\(7)16.4(,8)22.7(60)-235.5(D)12.9(a)0(\))-234.5(h)11.8(ad)-236.5(s)11.9(i)0(g)19.8(n)0(i)]TJ /F12 1 Tf 15.3906 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(nt)19.5(ly)-234.9(h)11.8(i)0(g)19.8(h)11.8(er)-234.5(in)19.2(te)19.8(ns)21.8(it)18.9(y)-240.2(i)0(n)]TJ -15.9098 -1.2114 TD [(ch)22(il)20.6(dr)18.7(en)-218.6(w)14.6(i)0(t)18.9(h)-226.9(KD)-216.3(th)21.4(an)-215.5(co)20.9(nt)19.5(r)11.9(o)0(l)16(s)11.9(,)-223.6(a)0(l)18.6(o)0(n)20.5(g)-228.3(w)14.6(i)0(t)18.9(h)-226.9(a)-225.4(s)11.9(ig)19.8(ni)]TJ /F12 1 Tf 19.4665 0 TD ()Tj /F11 1 Tf 0.5252 0 TD [(ca)23.5(nt)-219.2(d)12.7(i)0(f)79.6(f)0(e)20.7(r)11.9(en)20.1(ce)]TJ -19.9916 -1.2114 TD [(a)13.3(m)0(o)17(n)0(g)-385.5(a)0(c)17.5(u)12.7(te)-392(a)13.3(n)0(d)-389.1(s)11.9(ub)17.4(a)13.3(c)0(u)17(t)0(e)-386(K)0(D)-389.3(p)12.7(at)16.9(ie)19.6(nt)25.4(s.)-390.7(No)21.6(te)19.8(wo)19.3(r)11.9(t)0(h)21.4(y)0(,)-386.2(t)0(h)15.4(e)-395.6(p)12.7(e)0(a)17.5(k)11.6(,)]TJ T* [(wh)20.4(ic)19.6(h)-220.9(w)0(a)21.9(s)-226.8(i)15.3(d)0(e)17(n)0(t)19.5(i)]TJ /F12 1 Tf 6.5167 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ed)-209.8(as)-213.5(tr)21.5(un)16.7(ca)17.5(t)15.6(e)0(d)-215.8(f)0(o)21.2(r)11.9(m)-226.4(o)0(f)-211.6(S)0(A)21.1(A)-220.1(wi)18(th)-211.3(N-)18.8(te)19.8(r)11.9(m)12.3(in)19.2(al)-214.1(a)13.3(t)]TJ -7.0359 -1.2114 TD [(L)11.8(y)0(s)16.4(-)13.8(34)21.1(,)-295.2(d)12.7(is)21.3(ap)20.1(pe)17(ar)19.2(ed)-281.4(wh)20.4(en)-284.3(th)21.4(e)-294.2(s)11.9(ym)22.8(pt)16.4(om)23(s)-292.4(r)11.9(es)16.1(ol)21.9(ve)20.6(d.)-282.5(Mo)18.4(r)11.9(e)0(o)20.8(v)0(e)20.6(r)0(,)-283.3(t)0(h)21.4(e)]TJ 0 -1.2055 TD [(p)12.7(o)0(s)16.6(s)11.9(ib)20(il)20.6(it)18.9(y)-192.5(o)0(f)-181.7(e)0(x)-184.2(v)0(i)19.8(v)0(o)-181.8(S)0(A)21.1(A)-196.2(p)12.8(r)0(o)16.6(t)15.6(eo)20.9(ly)15.8(s)11.9(i)0(s)-181.6(w)0(a)21.9(s)-197(ex)18.7(cl)21.5(u)12.7(d)0(e)17(d)-196.1(by)-181.8(t)15.6(h)0(e)-186.9(p)12.7(re)16.1(s)11.9(e)0(n)20.1(c)0(e)]TJ 0 -1.2114 TD [(of)-122.1(th)21.4(e)-133(t)15.5(ru)18.7(nc)20.1(at)16.9(ed)-120.3(fo)21.2(r)11.9(m)-130.9(ev)14.7(en)-117.2(wh)20.4(en)-123.1(th)21.4(e)-133(b)0(l)21.9(o)0(o)21.3(d)-130.5(s)11.9(a)0(m)19.7(p)0(l)18.1(e)0(s)-121.1(w)0(e)18.8(r)11.9(e)-133(c)0(o)20.8(l)0(l)22.6(e)0(c)20.4(t)0(e)19.8(d)-130.5(in)]TJ T* 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[(d)12.7(i)0(s)15.3(c)0(o)20.8(v)0(e)20.6(r)11.9(ed)17(.)-408.6(M)0(o)18.4(r)11.9(eo)20.8(ve)20.6(r,)-402.7(it)-404.8(i)15.3(s)-411.8(im)15.7(p)12.7(o)0(r)22.6(t)0(a)16.9(n)0(t)-398.3(t)0(o)-403.5(u)12.8(nd)16.7(er)22.1(li)20.7(ne)-403.6(th)21.4(at)-400.8(fo)21.2(r)-411.8(t)0(h)21.4(e)]TJ 0 -1.2055 TD 0.0119 Tc [(peptide)-461.3(i)-2.6(dentity)-461.1(c)4.2(on)]TJ /F12 1 Tf 8.6054 0 TD 0 Tc ()Tj /F11 1 Tf 0.5371 0 TD 0.0113 Tc [(rmation)-462.2(t)-3(he)-461.9(hybrid)-465.3(mass)-460.2(sp)-5.8(ectrometry)]TJ -9.1424 -1.2114 TD 0 Tc [(im)21.7(mu)19.1(no)20.5(as)19.2(s)11.9(a)0(y)-417.9(t)0(e)19.8(c)0(h)22(n)0(i)19.2(q)0(u)21.5(e)-425.4(wa)15.9(s)-423.7(u)0(s)18.7(e)0(d)17(,)-420.5(si)15.3(nc)20.1(e)-425.4(a)-422.3(co)14.9(nv)20.3(en)20.1(ti)24.9(on)20.5(al)-417(EL)18.8(IS)19.2(A)]TJ T* 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[(a)-434.3(more)-438.3(intense)-442.2(SAA)-437.6(expression)-441.8(in)-440.3(the)-439.9(sarcoidosis)-443.1(granuloma)]TJ T* [(compared)-431.1(to)-433.3(other)-429.2(granulomatous)-434.1(diseases,)-436.5(suggesting)-430.2(it)-428.6(as)-434.3(a)]TJ T* [(diagnostic)-262.6(biomarker)-262.2(for)-259.3(sarcoidosis.)-260.9(SAA)-258.6(also)-257.2(emerged)-262.2(as)-261.2(a)-255.3(key)]TJ 0 -1.2055 TD [(protein)-259.9(regulating)-254.9(granulomatous)-261.1(in)]TJ /F12 1 Tf 14.4954 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammation)-255.4(through)-261.2(TLR-2.)]TJ -15.0266 -1.2114 TD [(Serum)-278.5(levels)-280.8(of)-277.2(SAA)-276.5(are)-280.9(increased)-282.2(in)-273.2(all)-280.4(sarcoidosis)-281.9(patients)-277.5(but)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT /F6 1 Tf 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD [(February)-305.6(2021)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(631299)]TJ -17.1054 0 TD (16)Tj ET endstream endobj 384 0 obj<> endobj 385 0 obj<> endobj 386 0 obj<> endobj 387 0 obj<> endobj 388 0 obj<> endobj 389 0 obj<> endobj 390 0 obj<> endobj 391 0 obj<> endobj 392 0 obj<> endobj 393 0 obj<> endobj 394 0 obj<> endobj 395 0 obj<> endobj 396 0 obj<> endobj 397 0 obj<> endobj 398 0 obj<> endobj 399 0 obj<> endobj 400 0 obj<> endobj 401 0 obj<> endobj 402 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 403 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 404 0 obj<>/Border[0 0 0]/Type/Annot>> endobj 405 0 obj<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 406 0 obj<>stream /GS1 gs BT /F11 1 Tf 9.5 0 0 9.5 45.3543 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[(sarcoidosis)-502.7(\(cut-of)64.4(f)-496.7(level)-501.6(of)-492.1(2.5)-500.9(mg/L\).)-496.8(However,)-499.7(the)-493.6(control)]TJ 0 -1.2055 TD [(samples)-232.6(in)-231.4(this)-231.9(cross-sectional)-239(study)-235(came)-228.5(from)-235.1(a)-231.4(cohort)-233.6(of)-229.5(a)-231.4(not)]TJ 0 -1.2114 TD 0.0275 Tc (well-de)Tj /F12 1 Tf 3.0733 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0273 Tc [(n)-4.6(e)1.7(d)-526.9(o)2.1(stensibly)-523.2(h)-2.7(ealthy)-523.2(don)-4.6(o)2.1(rs)-527.7(and)-526.9(t)1.1(he)-523.5(treatment)]TJ -3.6283 -1.2114 TD 0.0202 Tc [(administered)-522(to)-524.1(patients)-522.9(was)-522.9(n)0.2(ot)-525.2(reporte)-5.4(d)3.1(.)-525.7(I)1.1(n)-518.9(a)-521.5(study)-518.4(by)]TJ T* 0 Tc [(Miyoshi)-364.4(et)-362.1(al.)-366.1(\()]TJ 0 0 0 0.7 k 6.3197 0 TD (67)Tj 0 0 0 1 k 0.9548 0 TD [(\))-367.1(baseline)-366.8(SAA)-360.1(levels)-370.3(were)-364.9(not)-363.8(predictive)-364.7(for)]TJ -7.2746 -1.2114 TD 0.0195 Tc [(an)-519.6(increased)-516.8(l)1(ung)-513.1(i)-1(n)]TJ /F12 1 Tf 9.1663 0 TD 0 Tc ()Tj /F11 1 Tf 0.549 0 TD 0.0192 Tc [(ltration)-519.9(in)-519.9(patients)-517.9(with)-518(sarcoidosis,)]TJ -9.7153 -1.2114 TD 0.0275 Tc [(althou)4.4(gh)-521.6(SAA)-526.8(w)0.3(a)5(s)-527.5(not)-529.8(i)1.1(n)]TJ /F12 1 Tf 11.6071 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0264 Tc [(uenc)-5.2(ed)-527.8(by)-524.1(immuno)-4.7(suppressive)]TJ -12.1621 -1.2055 TD 0.0432 Tc [(therapy)-543.1(u)-3.7(n)5.3(l)-5.2(i)4.8(k)-4.9(e)-537.4(t)-0.9(he)-543.4(commonly)-543.1(used)-540.8(ACE)-546.6(\()-1.7(angiotensine-)]TJ 0 -1.2114 TD 0 Tc [(coverting)-396.7(enzyme\).)-390.3(On)-396.9(the)-392.1(other)-387.5(hand,)-396.7(Salazar)-395.6(et)-386(al.,)-392.8(Bargagli)]TJ T* [(et)-207(al.)-211(and)-208.8(Gungor)-209.1(et)-207(al.)-205(\()]TJ 0 0 0 0.7 k 9.4289 0 TD (68)Tj /F13 1 Tf 0 0 0 1 k 0.9548 0 TD ()Tj /F11 1 Tf 0 0 0 0.7 k 0.5132 0 TD (70)Tj 0 0 0 1 k 0.9608 0 TD [(\))-206(reported)-208.4(signi)]TJ /F12 1 Tf 6.0452 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-209.8(higher)-209(SAA)]TJ -18.4341 -1.2114 TD [(levels)-406.1(in)-398.5(patients)-402.8(with)-402.2(active)-408.4(sarcodiosis)-401.3(than)-403(in)-404.5(patients)-402.8(with)]TJ T* [(inactive)-245.9(disease.)-245.5(Moreover,)-247.3(Bargagli)-244.1(et)-242.8(al.)-240.8(\()]TJ 0 0 0 0.7 k 16.8825 0 TD (69)Tj 0 0 0 1 k 0.9608 0 TD [(\))-241.8(found)-247.8(a)-237.3(predictive)]TJ -17.8433 -1.2114 TD [(value)-377.7(of)-372.7(SAA)-372(for)-372.7(prolonged)-376.9(steroid)-377.2(requirement.)-381.1(Interestingly,)]TJ 0 -1.2055 TD [(proteomic)-230.6(analysis)-224.9(revealed)-226(two)-227.8(highly)-221.3(expressed)-233.9(SAA1)-227.2(isoforms)]TJ 0 -1.2114 TD [(in)-261.2(al)18.6(l)-269.2(o)0(f)-265.3(t)0(h)21.4(e)-276.2(s)11.9(a)13.3(rc)16.1(oi)20(d)12.7(o)0(s)16.6(i)15.3(s)-274.5(s)0(e)16.1(r)11.9(a)-273.2(a)13.3(nd)-263.8(in)-267.2(no)20.5(ne)-260.4(of)-265.3(t)15.6(h)0(e)-264.4(s)0(e)16.1(r)11.9(a)-273.2(f)0(r)22.4(o)0(m)-263.5(h)11.8(ea)17.5(lt)20.9(h)11.8(y)]TJ T* [(con)-11(trol)-10.3(s.)-456.4(The)-8.5(se)-461.3(SAA)-8(1)-452(i)0(s)-8.6(ofor)-10(ms)-459.1(cou)-8.2(ld)-459.3(matc)-8.3(h)-459.6(the)-457.8(uni)-9.8(den)-8.9(ti)]TJ /F12 1 Tf 24.1869 0 TD ()Tj /F11 1 Tf 0.5311 0 TD 0.0077 Tc (ed)Tj -24.718 -1.2114 TD 0 Tc [(bi)20(om)23(ar)19.2(k)11.6(e)0(r)-222.6(o)0(f)-223.5(s)0(a)19.2(r)11.9(co)20.8(id)16.1(os)22.6(is)-223.4(pr)18.7(ev)20.6(io)20(u)12.7(s)0(l)17.2(y)-228.3(re)16.1(p)12.8(o)0(r)16.6(t)0(e)19.8(d)-231.9(in)-219.5(a)-231.4(p)0(r)18.7(o)0(t)20.2(e)0(o)20.9(m)0(i)21.7(c)-234.5(s)11.9(t)0(u)16.4(d)12.7(y)]TJ T* [(by)-319.1(Bo)20.8(ns)-318.4(et)-314.4(al)18.6(.)-325.1(\()]TJ 0 0 0 0.7 k 6.1407 0 TD [(19)21.1(2)]TJ 0 0 0 1 k 1.4084 0 TD [(\).)-316.2(Th)17.1(e)-324(l)0(a)18.6(t)0(t)19.2(e)0(r)-318.1(g)0(r)22.3(o)0(u)17.4(p)-327.4(u)12.8(s)0(e)16.1(d)-327.4(SE)21.5(LD)18.7(I-)18.6(TO)22.2(F)-327.4(M)0(S)-318(a)0(n)17.2(d)]TJ -7.5491 -1.2114 TD [(r)11.9(e)0(p)17(o)0(r)22.6(t)0(e)19.8(d)-172.2(tw)18.2(o)-168.4(u)12.8(ni)19.2(de)17(nt)19.5(i)]TJ /F12 1 Tf 8.4144 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ed)-162.1(s)11.9(e)0(r)16.1(u)12.7(m)-172.7(p)12.7(ro)16.6(t)15.6(e)0(i)19.6(n)0(s)-163.2(t)0(h)21.4(a)0(t)-162.1(w)0(e)18.8(r)11.9(e)-168.8(u)0(p)19.5(-)0(r)19.8(e)0(g)20.6(u)0(l)18.1(a)0(t)16.9(e)0(d)-156.1(i)0(n)]TJ -8.9336 -1.2114 TD [(the)-445.8(sarcoidosis)-443.1(sera.)-444.8(The)-450.1(molecular)-445.1(weights)-441.3(of)-450.3(those)-441.2(proteins)]TJ 0 -1.2055 TD [(\(1)22.3(1,)16.7(9)13.5(9)0(5)-408.6(a)0(n)17.2(d)-422.9(1)13.5(1)0(,)16.7(7)13.5(34)-408.6(Da)20.2(\))-420.9(c)0(o)20.8(r)0(r)17.8(e)0(s)22.1(p)0(o)17.4(n)0(d)-407(t)0(o)-409.4(t)0(h)21.4(o)0(s)16.6(e)-419.5(of)-408.5(th)21.4(e)-419.5(t)0(w)18.2(o)-419(SA)21.1(A1)]TJ 0 -1.2114 TD [(is)21.3(of)21.2(or)16.6(m)12.3(s)-173.1(in)-159.8(th)21.4(e)-174.8(s)11.9(tu)16.4(d)12.7(y)-174.6(by)-158(Ba)17.4(r)11.9(g)0(a)17.8(g)0(l)21.7(i)-169.7(et)-165.2(a)13.3(l)0(.)-164.6(\()]TJ 0 0 0 0.7 k 14.9549 0 TD -0.0135 Tc (69)Tj 0 0 0 1 k 0.9369 0 TD -0.0154 Tc [(\).)-191.3(an)-15.4(d)-177.8(B)-15.4(o)5.4(n)-15.4(s)-178.6(e)-15.4(t)-180.6(a)-2.1(l)-15.4(.)-180(re)-15.4(po)-15.4(r)7.2(t)-15.4(ed)]TJ -15.8919 -1.2114 TD 0 Tc [(th)21.4(e)-234.5(h)0(i)21.2(g)0(h)-228.4(s)11.9(en)20.1(si)21.3(ti)18.9(vi)19.8(ty)-224.7(an)17.2(d)-231.9(s)0(p)18.7(e)0(c)20.4(i)]TJ /F12 1 Tf 11.2073 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ci)19.6(ty)-224.7(of)-229.5(th)21.4(es)22.1(e)-234.5(p)0(r)18.7(o)0(t)20.2(e)0(i)19.6(n)0(s)-222.9(f)0(o)15.2(r)-232.8(s)11.9(a)0(r)19.2(c)0(o)20.8(i)0(d)16.1(o)0(s)22.6(i)0(s)]TJ -11.7264 -1.2114 TD (\()Tj 0 0 0 0.7 k 0.3342 0 TD -0.0135 Tc [(19)-13.5(2)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc [(\).)-149.2(Zh)20(an)17.2(g)-156.7(e)0(t)-147.3(a)0(l)18.6(.)-158(\()]TJ 0 0 0 0.7 k 5.6335 0 TD -0.0135 Tc (71)Tj 0 0 0 1 k 0.9369 0 TD 0.1583 Tc [(\)c)158.3(o)179.1(n)]TJ /F12 1 Tf 1.9276 0 TD 0 Tc ()Tj /F11 1 Tf 0.5192 0 TD [(r)11.9(m)0(e)16.6(d)-154.3(th)21.4(at)-150.2(SA)21.1(A)-160.4(w)14.6(as)-147.9(si)15.3(gn)20.3(i)]TJ /F12 1 Tf 9.3692 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)23.5(nt)19.5(ly)-151.3(h)11.8(i)0(g)19.8(h)11.8(er)]TJ -20.6421 -1.2114 TD [(in)-356.7(th)21.4(e)-371.7(s)11.9(er)16.1(a)-368.6(f)0(r)22.4(o)0(m)-358.9(s)11.9(ar)19.2(co)20.8(id)16.1(os)22.6(is)-360.7(p)12.7(a)0(t)22.9(i)0(e)19.6(n)0(t)19.5(s)-370(co)20.9(m)12.3(p)0(a)14.1(r)11.9(ed)-359(to)-355.7(pa)20.1(ti)18.9(en)20.1(ts)-360.4(w)14.6(i)0(t)18.9(h)]TJ T* [(ot)20.2(h)11.8(e)0(r)-222.6(p)12.7(ul)18.1(m)12.3(o)0(n)20.5(a)0(r)19.2(y)-234.2(d)12.7(i)0(s)15.3(e)0(a)23.5(s)11.9(es)-222.6(in)19.2(cl)21.5(ud)19.5(in)19.2(g)-234.2(t)0(u)22.3(b)0(e)20.8(r)11.9(cu)17(lo)21.9(si)21.3(s)-232.8(\()0(t)18.4(h)11.8(e)-234.5(s)11.9(en)20.1(s)11.9(i)0(t)18.9(i)0(v)19.8(i)0(t)18.9(y)-228.3(of)]TJ 0 -1.2055 TD [(96)21.1(.3)22.7(%)-240.6(a)0(n)17.2(d)-237.9(sp)18.7(ec)20.4(i)]TJ /F12 1 Tf 6.2481 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ci)19.6(ty)-230.6(of)-229.5(52)21.1(.3)16.7(%)-234.7(a)0(t)-233.7(t)0(h)21.4(e)-240.4(cu)22.9(to)20.2(f)70.2(f)-240.1(va)23.7(lu)18.1(e)-240.4(o)0(f)-229.5(1)0(0)21.1(1)0(.)16.7(9)13.5(8)-243.1(m)12.3(g/)22.1(L\))20.6(.)]TJ -6.7673 -1.2114 TD [(Fu)19.5(r)11.9(t)0(h)21.4(e)0(r)16.1(m)12.3(or)16.6(e,)-117.9(by)-122.2(a)-129.9(p)12.7(ro)16.6(te)19.8(om)23(ic)-123.7(a)13.3(n)0(a)17.2(l)0(y)21.7(s)11.9(is)21.3(,)-134.1(a)-129.9(u)12.7(n)0(i)19.2(q)0(u)15.5(e)-127.1(pr)18.7(ot)20.2(ei)19.6(n)-133.3(p)12.7(ea)17.5(k)-125.7(o)0(f)-122.1(3)0(2)21.1(1)0(0)]TJ T* [(D)12.9(a)-165.7(w)14.6(i)0(t)18.9(h)-161.2(th)21.4(e)-162.9(h)11.8(ig)19.8(h)11.8(e)0(s)16.1(t)-157.5(ex)18.7(p)12.8(r)0(e)16.1(s)11.9(s)11.9(i)0(o)20(n)-163.2(in)-153.8(s)11.9(a)13.3(rc)16.1(oi)20(d)12.8(o)0(s)16.6(i)15.3(s)-161.2(s)0(e)16.1(r)11.9(a)-159.8(w)0(a)15.9(s)-161.2(r)11.9(e)0(v)20.6(e)0(a)17.5(l)0(e)21.5(d)12.7(.)-163.9(T)0(h)23.1(e)]TJ T* [(pe)17(a)13.3(k)-221.2(w)14.6(a)0(s)-213.5(i)0(d)22.1(e)0(n)20.1(t)0(i)]TJ /F12 1 Tf 5.9677 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ed)-209.8(as)-207.5(th)15.4(e)-216.6(N)0(-)18.8(t)0(e)19.8(r)11.9(m)12.3(i)0(n)19.2(a)0(l)-208.2(p)0(e)17(p)12.8(ti)18.9(de)-209.8(of)-211.6(2)13.5(9)-219.2(am)19.7(in)19.2(o)-216.1(a)0(c)17.5(i)0(d)22.1(s)-220.8(of)]TJ -6.4868 -1.2114 TD 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[(sa)13.3(rco)14.9(ido)14.9(si)15.3(s)-441.6(fro)15.2(m)-435.2(oth)14.1(er)-431.4(pu)13.6(lm)11.7(ona)15.9(ry)-437.2(di)16.1(sea)11.5(se)16.1(s.)-438.5(Co)16.2(ntr)13.5(ar)13.3(ily)19.1(,)-444.4(E)0(n)16.9(yed)15.5(i)]TJ 0 -1.2114 TD [(et)-296.5(a)13.3(l)0(.)-295.9(\()]TJ 0 0 0 0.7 k 2.5363 0 TD (72)Tj 0 0 0 1 k 0.9369 0 TD [(\))-307.5(r)0(e)16.1(p)12.7(or)22.6(te)19.8(d)-309.5(n)0(o)-295.8(d)12.8(if)79.6(fe)20.7(r)11.9(e)0(n)14.1(c)0(e)20.4(s)-304.4(in)-297.1(SA)21.1(A)-309.6(o)0(r)-293.7(C)0(R)22.8(P)-309.3(le)21.5(ve)20.6(ls)-299.1(be)20.8(t)15.6(w)0(e)18.8(e)0(n)]TJ -3.4732 -1.2114 TD 0.0096 Tc [(patien)-4.4(ts)-455.9(wi)-4.9(th)-456(biopsy-pr)9.6(o)-3.6(v)-3.8(e)1.9(n)-457.9(s)-2.4(arcoidos)9.6(i)-4.9(s)-461.9(and)-461(b)2.4(iops)9.6(y)-469.3(n)1.6(egati)-4.9(v)2.1(e)]TJ T* 0 Tc [(pa)20.1(ti)18.9(en)20.1(ts)21.5(.)-235.5(N)0(e)21.1(v)0(e)20.6(r)0(t)21.5(h)0(e)16(l)0(e)21.5(s)11.9(s,)-229.6(i)15.3(t)-235.1(mu)19.1(st)-223.2(be)-229.8(no)20.5(t)15.6(i)0(c)19.6(e)0(d)-227.7(t)0(h)21.4(a)0(t)-227.8(t)15.6(he)-228.6(la)24.6(tt)19.2(er)-228.5(gr)22.3(ou)23.4(p)-237.9(h)11.8(ad)]TJ T* [(hi)-8.7(sto)-9.6(logi)-12(cal)-460.5(di)-7.7(agn)-8.2(os)-7.3(es)-461.3(of)-456.2(l)-6.6(y)0(m)-7.1(phom)-12.1(a,)-455(c)-7.7(arci)-14.9(nom)-8.9(a,)-455(hi)-8.7(st)-8.3(iocy)-13.1(tos)-9.6(is,)]TJ T* 0.0184 Tc [(anthracosis,)-467.8(etc,)-473.8(all)-465.6(o)-0.8(f)-472.4(w)3.2(hich)-465.1(are)-466.7(a)1.9(s)-5.5(s)0.5(ociated)-470.1(w)3.2(ith)-471.1(i)-2.1(ncreased)]TJ 0 -1.2055 TD -0.0131 Tc [(ma)-13.1(r)6.1(k)-13.1(ers)-239.9(o)-13.1(f)-236.6(i)-13.1(n)]TJ /F12 1 Tf 5.2098 0 TD 0 Tc ()Tj /F11 1 Tf 0.5192 0 TD -0.0151 Tc [(am)-15.1(m)3.6(a)-15.1(ti)-15.1(o)4.9(n)-15.1(.)]TJ -4.4638 -1.2114 TD 0 Tc [(In)-349.4(light)-347.4(of)-354.8(these)]TJ /F12 1 Tf 6.8986 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ndings,)-350.4(the)-350.3(utilization)-356.2(of)-348.8(SAA1)-352.5(as)-350.8(well)-352.5(as)]TJ -8.6949 -1.2114 TD [(truncated)-275.8(SAA)-276.5(forms)-270.9(as)-273.2(markers)-274.9(for)-271.3(diagnosis,)-279.3(assessing)-275.2(disease)]TJ T* [(activity)-484.7(and)-489.2(response)-489.5(to)-481.1(therapy)-487(in)-482(patients)-492.3(with)-479.8(sarcoidosis)]TJ T* [(requires)-306.9(additional)-299.6(research.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 45.3543 118.148 Tm [(SAA)-301.8(IN)-302.3(OTHER)-303.6(INFLAMMATORY)]TJ 0 -1.1669 TD [(RHEUMATIC)-305.9(DISEASES)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 84.189 Tm [(SAA)-234.7(has)-231.5(been)-239.6(investigated)-237.1(in)-231.4(other)-238.3(rheumatic)-232.8(diseases)-242.7(as)-231.4(well,)-235.9(as)]TJ 0 -1.2114 TD [(shown)-299.2(in)]TJ /F14 1 Tf 0 0 0 rg 4.0162 0 TD [(Table)-304.8(6)]TJ /F11 1 Tf 0 0 0 1 k 3.1211 0 TD (.)Tj 21.579 67.1361 TD [(I)-7.2(n)-515.3(pa)-15.7(t)-8.3(i)-8.5(e)-7.7(n)-8(t)-8.3(s)-513.2(w)-9.3(i)-8.5(t)-8.3(h)-513.3(s)-12(y)-7.5(st)-14.3(e)-7.7(m)-11.5(i)-8.5(c)-515(sc)-13.7(l)-6.6(e)-7.7(r)-12(o)-7.3(si)-14.5(s)-519.2(\()-9.1(SS)-12.9(c)-7.7(\))-9.1(,)-516(S)-9.4(A)-11.2(A)-512.5(l)-6.6(e)-7.7(v)-7.5(e)-13.7(l)-6.6(s)-513.2(a)-10.6(r)0(e)]TJ -1.2651 -1.2114 TD [(elevated)-467.1(and)-459.4(correlate)-467.7(with)-461.9(disease)-463.4(severity.)-467.8(Brandwein)-465(et)-463.6(al.)]TJ T* (\()Tj 0 0 0 0.7 k 0.3461 0 TD (73)Tj 0 0 0 1 k 0.9548 0 TD [(\))-283.6(were)]TJ /F12 1 Tf 2.7869 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rst)-282.9(to)-284.1(investigate)-291.6(SAA)-282.5(as)-285.1(a)-285.1(marker)-286.8(of)-283.2(disease)-290.4(activity)]TJ -4.619 -1.2114 TD [(in)-273.2(SSc.)-280(The)-277(group)-275.7(reported)-280.1(elevated)-276.1(SAA)-276.5(concentrations)-282.5(in)-279.1(98%)]TJ T* [(of)-205.6(their)-209.7(patients)-205.9(and)-208.8(a)-207.5(signi)]TJ /F12 1 Tf 10.6642 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-207.7(correlation)-209.3(with)-205.3(disease)-206.8(severity)]TJ -11.1953 -1.2114 TD [(\(determined)-311.7(by)-313.1(extension)-309.7(of)-313(skin)-309.4(thickening\).)-315.4(Lakota)-311.7(et)-308.4(al.)-306.4(\()]TJ 0 0 0 0.7 k 24.36 0 TD (74)Tj 0 0 0 1 k 0.9548 0 TD (\))Tj -25.3148 -1.2055 TD [(included)-334.5(patients)-331.2(with)-330.6(limited)-336.9(and)-328.1(dif)62.5(fuse)-336.6(SSc)-330.9(in)-332.9(the)-326.5(study)-336.5(and)]TJ 0 -1.2114 TD [(found)-355.2(elevated)-353.7(SAA)-354.1(levels)-358.4(in)-350.8(25%)-356.8(of)-348.8(patients,)-357.9(while)-354.5(Lis)-354.8(Swiety)]TJ T* [(et)-350.2(al.)-354.2(\()]TJ 0 0 0 0.7 k 2.6675 0 TD (75)Tj 0 0 0 1 k 0.9608 0 TD [(\))-349.3(included)-358.4(only)-351.6(patients)-355.1(with)-348.5(dif)62.5(fuse)-354.5(SSc)-354.8(and)-352(detected)]TJ -3.6283 -1.2114 TD [(increased)-455.3(SAA)-455.6(levels)-453.9(in)-452.2(66%.)-449.1(The)-456.1(discrepancy)-456(between)-455.8(these)]TJ T* [(results)-248.7(may)-244.4(be)-241.7(explained)-247.9(by)-241.5(inclusion)-250.9(or)-240(exclusion)-251.4(of)-241.4(limited)-247.4(SSc)]TJ T* [(patients)-414.7(and)-411.7(dif)62.5(ferent)-415.1(SAA)-407.8(cut-of)61.6(f)-413.2(values)-413.5(between)-408.1(the)-410(studies.)]TJ 0 -1.2055 TD [(Furthermore,)-211(both)-208(of)-205.6(these)-202.9(studies)-214(found)-206(a)-207.5(signi)]TJ /F12 1 Tf 18.8697 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(cant)-201.7(correlation)]TJ -19.4068 -1.2114 TD [(between)-276.8(SAA)-270.6(levels)-274.8(and)-274.4(deterioration)-272.5(of)-277.2(lung)-271.9(function)-275.2(\(assessed)]TJ T* [(by)-295.2(forced)-291.9(vital)-292.2(capacity,)-301.6(dif)62.5(fusion)-293(capacity)-298.8(for)-295.1(carbon)-291.5(monoxide)]TJ T* [(or)-275.8(reticulation)-277.8(pattern)-274.9(on)-277.9(chest)-274.5(CT\).)-275.6(According)-278(to)-272.2(these)-280.5(studies,)]TJ T* [(SAA)-300.4(is)-295(superior)-302.5(to)-296.1(CRP)-298.5(as)-297(a)-297(marker)-298.8(of)-295.1(pulmonary)-300.5(involvement)]TJ T* [(in)-267.2(SSc.)-268(Still,)-269.1(longitudinal)-269.3(studies)-267.7(are)-268.9(needed)-268.2(to)-266.2(validate)-267.9(SAA)-270.6(as)-267.2(a)]TJ 0 -1.2055 TD [(marker)-340.5(of)-336.9(disease)-338.1(activity,)-344.3(predictor)-336.3(of)-342.9(disease)-338.1(progression)-344(and)]TJ 0 -1.2114 TD [(response)-304.5(to)-302(therapy)-302(in)-303(SSc.)]TJ 1.2651 -1.2114 TD [(The)-342.7(only)-351.6(article)-347.9(reporting)-350.9(on)-343.5(SAA)-348.1(in)-350.8(SLE)-342.7(patients)-355.1(that)-343.6(was)]TJ -1.2651 -1.2114 TD [(found)-361.2(through)-368.6(comprehensive)-365.5(literature)-367.3(search)-366.3(is)-360.7(the)-362.3(study)-360.3(by)]TJ T* [(Wang)-406.8(et)-409.9(al.)-401.9(\()]TJ 0 0 0 0.7 k 5.5917 0 TD (76)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-405.8(The)-408.3(group)-407(revealed)-411(a)-404.4(signi)]TJ /F12 1 Tf 12.1203 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-404.6(correlation)]TJ -19.2039 -1.2114 TD [(between)-247(SAA)-246.7(levels)-251(and)-250.5(SLE)-247.2(disease)-248.6(activity)-246(\(determined)-252(by)-247.5(SLE)]TJ T* [(disease)-206.8(activity)-198.3(score)]TJ /F13 1 Tf 8.1399 0 TD ()Tj /F11 1 Tf 0.919 0 TD [(SLEDAI\).)-204.9(Although)-201.4(SAA)-198.9(was)-204.9(signi)]TJ /F12 1 Tf 13.6659 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (cantly)Tj -23.256 -1.2055 TD [(correlated)-389.3(with)-390.3(serum)-388.5(levels)-394.2(of)-384.6(hs-CRP)-392.2(\(high)-389.4(sensitivity)-389.3(CRP\))]TJ 0 -1.2114 TD [(and)-322.1(ESR,)-322.2(a)-320.9(binary)-328.4(logistic)-323(regression)-327.3(analysis)-320.4(showed)-327.9(that)-319.8(SAA)]TJ T* [(values)-359.8(are)-358.5(independently)-368.1(associated)-358.3(with)-360.5(active)-360.7(SLE.)-357.4(Since)-363.7(this)]TJ T* [(research)-505.4(was)-497.3(retrospective)-505.7(and)-501.2(cross-sectional,)-504.4(a)-499.9(prospective,)]TJ T* [(l)-6.6(o)0(n)-9.3(g)0(i)-10.1(t)0(u)-7.5(d)0(i)-13.7(nal)-13.3(,)-510.1(lar)-11.3(g)-7.5(e)-509(c)-7.7(o)0(h)-7.4(o)-7.3(rt)-509.6(st)-14.3(ud)-10.3(y)-508.8(i)0(s)-515.8(n)0(e)-9.8(c)0(e)-9.4(s)0(s)-12(ary)-519.4(to)-510.9(c)-7.7(o)0(n)]TJ /F12 1 Tf 22.1758 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(rm)-512.9(th)-8.4(e)]TJ -22.7129 -1.2114 TD [(clinical)-303(utility)-303.6(of)-301.1(SAA)-300.4(for)-301.1(monitoring)-301.8(SLE)-300.9(patients.)]TJ 1.2651 -1.2055 TD 0.0376 Tc [(Boyd)-540.5(et)-537.6(al.)-538.1(\()]TJ 0 0 0 0.7 k 6.0214 0 TD 0.0402 Tc (77)Tj 0 0 0 1 k 1.0384 0 TD 0.0384 Tc [(\))-537.6(r)2.6(e)-5.1(p)3.4(orted)-539.7(t)0.2(hat)-536.8(a)-2(mo)-4.7(ng)-536(15)-538.9(biomarkers)]TJ -8.3249 -1.2114 TD 0 Tc [(\(including)-360.8(CRP\),)-358.1(SAA)-354.1(levels)-358.4(were)-358.9(most)-355.4(signi)]TJ /F12 1 Tf 18.3804 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-353.1(correlated)]TJ -18.9115 -1.2114 TD [(with)-420.1(disease)-421.7(activity)-425(in)-422.4(patients)-420.7(with)-420.1(psoriatic)-426.2(arthritis)-426.4(\(PsA\).)]TJ T* [(However,)-422.1(the)-416(study)-426(was)-413.8(cross)-420.8(sectional)-422.8(in)-422.4(a)-416.4(small)-423.3(cohort)-418.6(\(45)]TJ T* 0.009 Tc [(pa)9(t)-9.9(i)0.5(ents\))-507.3(a)-1.6(nd)-509.4(inc)-4.7(l)2.4(uded)-509.4(p)-2.1(a)9(t)-3.9(i)-5.5(e)1.3(nts)-510.2(r)9(e)-10.7(ceiv)-4.4(i)0.5(ng)-511.7(d)9(i)-4.7(f)61.3(f)-4.4(er)9(e)-10.7(n)1(t)-506.6(t)0.7(herap)9(i)-4.7(e)-4.7(s)]TJ T* 0 Tc [(\(including)-474.2(conventional)-477.5(and)-471.3(biological)-471.7(DMARDs\).)-473.7(Moreover,)]TJ T* 0.0159 Tc [(di)-4.6(se)-3.7(ase)-517(a)-6.6(ct)-4.4(ivit)-4.4(y)-516.7(a)-0.6(sse)-3.7(ssme)-3.7(n)-4.1(t)]TJ 12.0368 0 TD 0.0164 Tc [(did)-519.9(n)-3.6(ot)-517.1(include)-516.5(ankle)-522.4(a)-0.1(nd)-519.9(feet)]TJ -12.0368 -1.2055 TD 0 Tc [(invo)-7.4(lvement)-510.9(that)-504.7(are)-507.7(frequ)-11.6(ently)-503.6(se)-7.7(en)-505.1(in)-500(PsA)-10.2(.)-498.1(Futu)-11.9(re)-503(stu)-7.5(dies)]TJ 0 -1.2114 TD 0.0139 Tc [(should)-516.4(t)5.6(h)1.8(erefore)-513(v)0.5(alidat)5.6(e)-513(t)-0.4(he)-507(ut)5.6(ility)-506.8(o)0.7(f)-512.7(S)4.5(AA)-510.5(in)-507.3(monito)6.6(ri)5.4(ng)]TJ T* 0 Tc [(PsA)-302.6(patients.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 210.1606 Tm [(SAA)-301.8(IN)-302.3(SYSTEMIC)-301.6(AUTOINFLAMMATORY)]TJ 0 -1.1669 TD (DISEASES)Tj /F11 1 Tf 9.5 0 0 9.5 306.1417 176.1448 Tm 0.0253 Tc [(A)-3.8(m)1.8(o)-5.8(n)-0.6(gs)-4.6(t)-520.1(t)-0.9(h)-4.7(e)-519.5(sy)-6(ste)-6.3(m)1.8(i)-7.1(c)-519.5(aut)-6.9(o)0.1(in)]TJ /F12 1 Tf 13.0751 0 TD 0 Tc ()Tj /F11 1 Tf 0.561 0 TD 0.0283 Tc [(am)4.8(matory)-516.3(diseas)4.4(es)-514.8(\(SAID\),)]TJ -13.6361 -1.2114 TD 0.0609 Tc [(the)-549.5(c)-0.5(li)4.6(nical)-548.4(u)-3.9(t)4.8(i)-1.4(lit)4.8(y)-555.3(o)5.9(f)-555.2(SAA)-553.1(h)1.1(as)-547.8(been)-549.9(most)-550.1(extensiv)5.7(ely)]TJ 0 -1.2055 TD 0.0087 Tc [(inve)-5(s)8.7(t)-5.6(igated)-378.4(in)-375.3(patients)-379.2(with)-373.4(FMF.)-376(SA)8.7(A)-383.7(l)2.1(e)-5(v)1.2(els)-379.2(a)-1.9(r)8.7(e)-381(e)-5(l)2.1(evated)-378.4(in)]TJ 0 -1.2114 TD 0 Tc [(F)-11.1(M)0(F)-242.1(p)0(a)-15.7(t)-8.3(i)-8.5(e)-7.7(n)-14(t)-8.3(s)-232.8(n)-8(o)-7.3(t)-235.1(o)-7.2(n)-8(l)-12.6(y)-234.2(du)-16.3(ri)-14.5(n)-14(g)-234.2(at)-12.9(t)-8.3(a)-10.6(c)-7.7(k)-12.3(s,)-241.5(b)-7.3(u)-11.1(t)-235.1(a)0(l)-17.2(s)0(o)-240(i)-8.5(n)-234.8(t)-8.3(he)-240.6(a)-10.6(t)-8.3(t)-8.3(a)-10.6(c)-7.7(k)0(-)-16.3(f)-7.4(r)-12(e)-7.7(e)]TJ T* 0.0578 Tc [(period)-550.1(revealing)-546.4(a)-549.5(sustained)-544.1(s)-1.9(ubcl)3.5(inical)-551.5(in)]TJ /F12 1 Tf 20.29 0 TD 0 Tc ()Tj /F11 1 Tf 0.5908 0 TD 0.0573 Tc (ammation.)Tj -20.8808 -1.2114 TD 0.0253 Tc 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[(resp)5.4(onse)-534.2(to)-539.7(ril)4(o)3.3(nacept)-534.8(t)-3.7(h)4.5(e)2.9(rapy)-534(is)-532.5(better)-538.5(c)2.9(orr)4.6(e)-3.1(l)4(a)0(ted)-537.6(w)1.3(ith)]TJ T* 0 Tc [(improvement)-345.9(in)-344.8(clinical)-344.8(symptoms)-343.8(than)-343.3(CRP)-346.2(or)-341.5(ESR)-343.2(levels.)-343.3(In)]TJ T* [(cases)-419.9(of)-420.4(reoccurrence)-424.8(of)-420.4(disease)]TJ /F12 1 Tf 13.6122 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(are,)-420.9(SAA)-419.8(levels)-424(signi)]TJ /F12 1 Tf 8.5815 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (cantly)Tj -23.256 -1.2055 TD 0.0137 Tc [(increased)-516.6(d)-3.4(espite)-519.2(the)-513.2(r)-4.2(ilon)-6.3(ace)-5.9(p)2.6(t)-513.8(t)-0.6(reatme)-5.9(nt.)-514.3(W)-3(iken)-519.5(an)-6.3(d)-510.6(c)-5.9(o-)]TJ 0 -1.2114 TD 0 Tc [(workers)-335(\()]TJ 0 0 0 0.7 k 3.8551 0 TD (97)Tj 0 0 0 1 k 0.9608 0 TD [(\))-331.3(con)]TJ /F12 1 Tf 2.1305 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rmed)-340.7(utility)-333.5(of)-336.9(SAA)-336.2(as)-332.9(a)-332.8(marker)-340.5(of)-330.9(response)]TJ -7.4775 -1.2114 TD 0.0585 Tc [(to)-563.4(anakinra)-560.8(in)-558.2(M)-5.4(W)0.1(S)-559.6(a)0.2(nd)-561.3(neonatal)-556.8(onset)-558.5(m)-0.8(ultisystem)]TJ T* 0.0085 Tc (in)Tj /F12 1 Tf 0.8235 0 TD 0 Tc ()Tj /F11 1 Tf 0.5371 0 TD 0.0111 Tc [(ammatory)-509.6(disease)-509.8(\()2(NOMID\))-505.2(patients)11.1(,)-516.9(a)0.5(s)-508.1(w)1.8(el)4.5(l)-508.7(a)0.5(s)-508.1(a)-512.7(h)11.1(i)-3.5(gh)]TJ -1.3606 -1.2114 TD 0 Tc [(in)-10.6(cid)-9.5(e)-7.7(nce)-512.8(of)-510(an)-12.6(ti-)-9(dr)-11.2(ug)-507.9(ant)-15(ibo)-11.1(di)-7.7(es)-509(de)-12.9(vel)-9.9(opm)-12(en)-9.8(t,)-506.4(b)-7.3(u)0(t)-508.8(w)0(i)-11.9(t)0(h)-509.7(n)0(o)]TJ T* (in)Tj /F12 1 Tf 0.7997 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(uence)-352.6(on)-349.5(ef)]TJ /F12 1 Tf 4.6965 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cacy)-349.8(of)-342.9(anakinra)-355.1(or)-347.4(SAA)-348.1(levels.)-349.3(These)]TJ /F12 1 Tf 15.8859 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (ndings)Tj -22.9755 -1.2055 TD [(highlight)-405.4(the)-404(potential)-410.7(utility)-405.1(of)-408.5(SAA)-401.8(in)-410.4(assessing)-406.5(response)-411.9(to)]TJ 0 -1.2114 TD [(biologic)-460.5(therapy)-469.1(in)-464.1(MWS)-459.9(and)-465.4(NOMID)-460(patients.)-471.3(The)-462(articles)]TJ T* [(discussed)-308.1(in)-297.1(this)-303.5(section)-304.2(are)-298.8(summarized)-306.7(in)]TJ /F14 1 Tf 0 0 0 rg 17.8612 0 TD [(Table)-298.8(7)]TJ /F11 1 Tf 0 0 0 1 k 3.1211 0 TD (.)Tj /F1 1 Tf 11.9999 0 0 11.9999 45.3543 292.8755 Tm [(SAA)-301.8(IN)-302.3(SECONDARY)-304.6(\(AA\))-298.7(AMYLOIDOSIS)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 272.8629 Tm [(The)-330.8(association)-327.5(between)-330.5(SAA)-330.2(and)-328.1(secondary)-328.5(\(AA\))-333(amyloidosis)]TJ 0 -1.2114 TD [(was)-360(one)-363.1(of)-360.8(the)]TJ /F12 1 Tf 6.4212 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(rst)-360.5(investigated)-368.4(roles)-361.8(of)-360.8(SAA,)-362.9(with)-360.5(many)-365.8(new)]TJ -6.9583 -1.2114 TD [(studies)-500.4(still)-501.6(emerging)-500.1(\()]TJ /F14 1 Tf 0 0 0 rg 9.7392 0 TD [(Table)-501.7(8)]TJ /F11 1 Tf 0 0 0 1 k 3.324 0 TD [(\).)-495.3(Amyloidosis)-503.3(is)-497.9(a)-494(single-)-502(or)]TJ -13.0632 -1.2055 TD 0.0465 Tc [(multiorgan)-546.4(disease)-546(c)-3(haracter)]TJ 13.2124 0 TD 0.0482 Tc [(i)3.8(zed)-541.8(by)-544.1(e)4.7(x)-3(t)4.1(r)0.4(ac)4.7(ell)5.8(u)1.3(lar)-542.6(t)-1.9(i)3.9(ssue)]TJ -13.2124 -1.2114 TD 0 Tc [(deposition)-406.1(of)-402.5(low-molecular)-406.7(weight,)-402.3(insoluble)-409.3(and)-399.7(amorphous)]TJ T* [(proteinaceous)-381.9(material,)-377(causing)-375.7(progressive)-379.7(organ)-379.5(dysfunction.)]TJ T* [(Rheumatic)-293.1(and)-292.3(autoin)]TJ /F12 1 Tf 8.9575 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-294.1(diseases)-296.4(are)-292.8(associated)-292.7(with)-294.8(a)]TJ -9.4886 -1.2114 TD [(high)-260.9(rate)-259.4(of)-259.3(secondary)-262.8(\(AA\))-261.4(amyloidosis.)-260.8(As)-261.9(already)-263(mentioned,)]TJ T* [(S)-9.4(A)0(A)-517.8(g)-7.5(e)-13.7(n)0(e)-517(p)-11.1(o)-7.3(l)-6.6(y)-7.5(m)0(o)-12.8(r)-12(ph)-11.2(i)-8.5(s)0(m)-17.5(s)-513.2(ha)-16.7(v)-7.5(e)-515(an)-519.9(i)-8.5(n)]TJ /F12 1 Tf 16.2977 0 TD ()Tj /F11 1 Tf 0.5371 0 TD 0.0079 Tc [(uen)7.9(c)-1.9(e)-507.1(o)0.7(n)-507.4(d)-3.2(evelop)7.9(i)-5.8(n)-0.1(g)]TJ -16.8348 -1.2055 TD 0.0657 Tc [(amyloidosis.)-569.7(Th)5.9(e)-568.6(s)0(trong)-562.4(c)-1.7(orrelation)-563(between)-568.9(a)1.4(myl)5.4(o)-1.2(id)]TJ 0 -1.2114 TD 0.0184 Tc [(de)-7.2(position)-520.7(and)-523.8(S)-2.9(AA1)]TJ /F17 1 Tf 9.3752 0 TD 0 Tc (g)Tj /F11 1 Tf 0.9429 0 TD 0.0192 Tc [(allele)-519.6(in)-519.9(Japanese)-519.6(RA)-523.1(patients)-523.9(was)]TJ -10.3181 -1.2114 TD 0 Tc (con)Tj /F12 1 Tf 1.4561 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rmed)-340.7(by)-331(Ishii)-334.7(et)-338.3(al.)-336.3(\()]TJ 0 0 0 0.7 k 8.4621 0 TD (99)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-334.1(Furthermore,)-342.3(the)-332.4(group)-335.4(reported)]TJ -11.4102 -1.2114 TD (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-317.3(higher)-316.4(SAA)-318.3(levels)-316.6(in)-320.9(RA)-316.2(patients)-319.3(with)-318.7(amyloidosis)]TJ -2.4169 -1.2114 TD [(than)-325.4(in)-320.9(those)-321.8(without.)-324.3(SAA)-324.3(showed)-322(a)-320.9(stronger)-325.3(correlation)-322.7(with)]TJ T* [(the)-260.8(presence)-264.9(of)-259.3(amyloid)-266(deposits)-263(than)-259.8(CRP.)-259.5(However,)-266.9(according)]TJ T* [(to)-487(the)-487.6(most)-486.7(of)-486.1(published)-487.3(reports,)-490.8(SAA)-491.4(serum)-484(levels)-489.7(are)-489.8(not)]TJ 0 -1.2055 TD [(correlated)-401.2(with)-396.3(the)-392.1(presence)-402.1(of)-396.6(amyloid)-397.3(deposits)-400.3(\()]TJ 0 0 0 0.7 k 20.8629 0 TD (43)Tj 0 0 0 1 k 0.9548 0 TD (,)Tj 0 0 0 0.7 k 0.6147 0 TD (44)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.6147 0 TD (100)Tj 0 0 0 1 k 1.4322 0 TD (,)Tj 0 0 0 0.7 k -25.4401 -1.2114 TD (101)Tj 0 0 0 1 k 1.4382 0 TD [(\).)-304.3(Therefore,)-310(contrary)-306(to)-302(expectations,)-312.4(high)-302.7(SAA)-306.4(levels)-310.7(are)-304.8(a)]TJ 26.013 66.6408 TD 0.0238 Tc [(pr)5.9(er)5.9(equ)6.7(i)-2.7(s)5.9(i)3.3(t)3.5(e)-1.8(,)-516.1(b)4.6(ut)-521.6(n)3.8(o)4.6(t)-521.6(a)-517.9(s)5.9(u)0.7(f)]TJ /F12 1 Tf 11.7205 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0204 Tc [(cien)-5.5(t)-519(c)0.8(o)-4.8(n)0.4(dition)-524.7(fo)-4.8(r)-516.7(d)-2.7(e)-5.2(v)1(eloping)]TJ -12.2755 -1.2114 TD 0 Tc [(amylo)-7.7(id)-7.7(os)-7.3(is)-503.9(and)-513.1(canno)-11.7(t)-503.6(b)0(e)-504.3(used)-513.4(as)-505.9(a)-505.9(diagn)-9.9(os)-7.3(tic)-507.9(mark)-10.6(er)-503.1(f)-7.4(o)0(r)]TJ T* [(amyloidosis.)-326.5(It)-325.8(is)-324.9(possible)-329(that)-319.8(increased)-330(proteolytic)-331(cleavage)-322.4(of)]TJ T* [(SAA)-491.4(contributes)-492.1(to)-487(the)-487.6(development)-488.5(of)-492(amyloidosis.)-493.6(Indeed,)]TJ T* [(Migita)-358(et)-356.2(al.)-360.1(\()]TJ 0 0 0 0.7 k 5.6454 0 TD (100)Tj 0 0 0 1 k 1.4322 0 TD [(\))-361.2(detected,)-359(in)-362.7(addition)-360(to)-355.7(the)-356.3(full-length)-360.5(SAA)]TJ -7.0776 -1.2114 TD [(protein,)-209(6)-201.3(kDA)-207.6(and)-202.8(4.5)-208.5(kDa)-206.9(SAA-derived)-209(fragments)-210.3(in)-201.6(the)-207.1(sera)-203.3(of)]TJ 0 -1.2055 TD [(RA)-483.3(patients.)-489.2(The)-485.9(ratio)-482.3(of)-486.1(these)-489.4(fragments)-484.8(to)-487(total)-482.7(SAA)-485.4(was)]TJ 0 -1.2114 TD 0.0135 Tc (signi)Tj /F12 1 Tf 1.9514 0 TD 0 Tc ()Tj /F11 1 Tf 0.5431 0 TD 0.0135 Tc [(cantly)-513.2(higher)-511.7(in)-513.7(pat)5.2(i)-1(ents)-511.7(wit)5.2(h)-511.8(than)-513.7(i)5(n)-513.7(those)-513.4(w)-1.8(ithout)]TJ -2.4945 -1.2114 TD 0 Tc [(amyloidosis,)-511.5(con)]TJ /F12 1 Tf 6.9105 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(rmi)-8.2(ng)-498.9(the)-505.5(increased)-509(proteolysis)-506(hypothesis.)]TJ -7.4417 -1.2114 TD [(The)-396.4(potential)-404.7(use)-400.8(of)-396.6(these)-399.8(truncated)-401.2(SAA)-401.8(forms)-396.2(as)-398.5(diagnostic)]TJ T* [(markers)-304.8(for)-301.1(amyloidosis)-305.8(should)-298.8(be)-301.4(further)-303.3(investigated.)]TJ 1.2651 -1.2114 TD [(Subsequent)-509.6(studies)-506.4(in)-505.9(amyloidos)-10.7(is)-497.9(pati)-8.7(ents)-501.5(revea)-9.6(led)-502.8(some)]TJ -1.2651 -1.2055 TD [(clinically)-317.1(important)-318.4(properties)-318.5(of)-319(SAA.)-315.1(Although)-314.8(SAA)-318.3(may)-316(not)]TJ 0 -1.2114 TD 0.022 Tc [(be)-522.8(a)-525.7(d)4.9(iagnostic)-522.8(o)2.8(r)-527.1(p)4.9(redictive)-522.8(m)-1.5(ark)3.7(e)-3.6(r)-521.1(o)2.8(f)-522.5(a)-0.5(myoidosis,)-523.9(once)]TJ T* 0 Tc [(amyloidosis)-419.1(has)-416.5(developed,)-420.8(the)-421.9(SAA)-413.8(levels)-418.1(over)-422.3(the)-416(course)-415.8(of)]TJ T* 0.013 Tc [(the)-513.9(d)1.9(isease)-513.9(represent)-508.5(t)-1.3(he)-513.9(main)-514.2(factor)-512.2(af)59.3(fec)5.3(t)-1.3(ing)-513.7(a)2.4(myloidosis)]TJ T* 0.0245 Tc [(progress)-5.4(ion)-526.6(a)2(nd)-523.7(s)-5.4(u)1.4(rvival.)-527.3(T)0(he)-526.3(kid)-4.5(n)-1.4(ey)-520.1(is)-524.6(one)-526.3(o)5.3(f)-525.9(t)-1.7(he)-526.3(most)]TJ T* 0 Tc [(frequent)-495.1(sites)-496.1(of)-492(amyloid)-492.8(deposition)-495.7(and,)-498(without)-494.6(treatment,)]TJ 0 -1.2055 TD [(amyloidosis-associated)-262.3(kidney)-258.1(disease)-254.6(usually)-256.5(progresses)-256.3(to)-254.3(end-)]TJ 0 -1.2114 TD 0.0122 Tc [(stage)-508.7(r)0.2(enal)-507.6(d)-4.9(i)3.7(sease)-514.7(\()3.1(ESRD\).)-515.8(Pr)]TJ 13.3258 0 TD 0.0119 Tc [(ognosis)-507.3(o)-1.3(f)-514.7(r)-0.1(enal)-513.9(amyloidosis)]TJ -13.3258 -1.2114 TD 0 Tc (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-329.2(correlates)-336.4(with)-330.6(the)-332.4(SAA)-330.2(concentration.)-339(Falck)-328.8(et)-332.3(al.)]TJ -2.4169 -1.2114 TD (\()Tj 0 0 0 0.7 k 0.3461 0 TD (6)Tj 0 0 0 1 k 0.4774 0 TD [(\))-474.6(and)-477.3(Lachmann)-474.4(et)-475.5(al.)-473.5(\()]TJ 0 0 0 0.7 k 10.4315 0 TD (102)Tj 0 0 0 1 k 1.4382 0 TD [(\))-474.6(reported)-477(a)-476.1(strong)-472.7(correlation)]TJ -12.6932 -1.2114 TD [(between)-336.5(the)-338.4(mean)-336.2(SAA)-336.2(value)-335.9(and)-340(changes)-334.1(in)-338.8(renal)-337.3(function)-340.9(in)]TJ T* [(patients)-373(with)-366.4(renal)-373.1(amyloidosis,)-374.2(suggesting)-370.6(SAA)-372(for)-366.8(predicting)]TJ T* [(renal)-361.2(deterioration.)-358.8(Reportedly,)-363.3(renal)-361.2(improvement)-357.8(is)-360.7(expected)]TJ 0 -1.2055 TD [(when)-287.7(SAA)-282.5(median)-290.3(is)-283.1(less)-282.9(than)-289.6(6)-284.9(mg/ml)-282.1(and)-286.3(deterioration)-290.4(when)]TJ 0 -1.2114 TD [(SAA)-300.4(median)-302.2(is)-301(above)-302.8(28)-301.2(mg/L.)]TJ 1.2651 -1.2114 TD 0.0207 Tc [(Furt)-5.5(h)2.7(e)-4.9(r)-3.2(mor)-3.2(e)1.1(,)-525.2(S)-0.7(AA)-527.6(le)-4.9(ve)-4.9(ls)-528.4(ar)-3.2(e)-524.1(s)2.8(i)-5.7(g)1.3(n)-5.2(i)]TJ /F12 1 Tf 15.1638 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0208 Tc 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[(SAA)-512.1(l)5.7(ev)4.9(el)5.7(s)-512.9(w)3.1(er)6.3(e)-514.6(s)0.4(t)4(i)3.8(ll)-513.5(h)6.2(i)3.8(gh)6.2(er)-512.9(t)4(h)0.3(an)-508.9(i)3.8(n)-514.9(pat)4(i)3.8(en)4.3(t)4(s)-512.8(wit)4(h)-512.9(de)4.6(po)5.1(si)3.8(t)]TJ T* 0 Tc [(regression.)-497.2(According)-498.8(to)-493(a)-494(large)-491.9(cohort)-496.2(prospective)-500.7(study)-491.6(of)]TJ T* 0.0181 Tc [(am)-5.4(yloidosis)-519(b)-1.1(y)-520.5(L)0.1(achm)-5.4(ann)-521(e)4.4(t)-521.3(a)1.6(l.)-521.8(\()]TJ 0 0 0 0.7 k 14.9967 0 TD 0.0163 Tc (102)Tj 0 0 0 1 k 1.4919 0 TD 0.02 Tc [(\))4.9(,)-519.9(pati)5.5(ents)-517.1(w)4.8(i)-0.5(th)-517.2(SAA)]TJ -16.4886 -1.2114 TD 0.0316 Tc [(concentrations)-535.4(in)-531.4(t)5.4(h)-4.3(e)-531.1(l)1.1(ow-normal)-530(r)-4.2(ange)-531.1(\(<4)-533.7(m)2.2(g/L\))-526.5(have)]TJ T* 0 Tc [(relatively)-357.5(favorable)-363.3(outcome,)-356.1(while)-360.5(persistent)-358.2(elevation)-364.6(of)-354.8(SAA)]TJ T* 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[(an)17.2(d)-184.2(L)11.8(an)17.2(e)-186.7(e)0(t)-171.2(a)0(l)18.6(.)-187.8(\()]TJ 0 0 0 0.7 k 6.0452 0 TD -0.0135 Tc [(10)-13.5(7)]TJ 0 0 0 1 k 1.4024 0 TD 0 Tc [(\))-188.1(s)11.9(tu)16.4(d)12.7(i)0(e)19.6(d)-190.2(t)15.6(h)0(e)-180.9(e)0(f)]TJ /F12 1 Tf 5.6633 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(cy)-176.3(of)-175.8(t)15.6(o)0(c)20.8(i)0(l)20.7(i)0(z)19.6(u)0(m)19.1(a)0(b)-179(\()0(T)20.1(C)0(Z)19.7(,)-181.8(an)17.2(ti)18.9(-)]TJ -13.6301 -1.2114 TD [(IL)22.6(-6)-372.5(r)11.9(e)0(c)20.4(e)0(p)17(t)15.6(or)-371.3(an)17.2(t)15.6(i)0(b)20(o)0(d)17.4(y)0(\))-368.7(i)0(n)-368.7(p)12.7(at)16.9(ie)19.6(nt)19.5(s)-376(w)0(i)18(t)0(h)-366.5(A)12.7(A)-381.2(a)0(m)19.7(y)0(l)21.7(o)0(i)20(d)0(o)17.4(s)11.9(is)21.3(.)-378.8(I)0(n)-367.3(a)0(l)18.6(l)]TJ T* 0.0161 Tc [(pati)-4.4(en)-3.9(ts,)-470.1(S)0.7(AA)-466.6(lev)-3.3(e)2.4(ls)-467.3(sig)-3.3(n)2.1(i)]TJ /F12 1 Tf 11.0223 0 TD 0 Tc ()Tj /F11 1 Tf 0.549 0 TD 0.0183 Tc [(can)4.3(t)-2(l)5.7(y)-466.6(dec)4.6(r)0.4(eas)6.3(e)-1.3(d)-464.3(t)-2(o)5.1(g)-1.1(e)4.6(t)4(her)-465.1(w)3.1(i)3.8(t)-2(h)-465.2(a)]TJ -11.5713 -1.2055 TD 0.0268 Tc [(remarkable)-482.2(decrease)-476.2(i)-5.6(n)-476.5(pro)-4.3(t)0.6(ein)-5.1(u)-2.2(ria,)-483.3(re)-4.8(gressio)-4.3(n)-476.5(of)-481.9(amy)-4.5(l)2.3(o)-4.3(i)0.4(d)]TJ 0 -1.2114 TD 0.0134 Tc [(dep)-3.7(o)6.1(s)-4.5(i)4.9(ts)-464(and)-463.2(s)1.4(igni)]TJ /F12 1 Tf 7.758 0 TD 0 Tc ()Tj /F11 1 Tf 0.549 0 TD 0.0129 Tc [(c)5.2(a)-3.6(nt)-460.9(improvement)-460.9(i)-1.6(n)-466.6(c)5.2(linical)-465.2(s)0.9(ymptoms.)]TJ -8.307 -1.2114 TD 0 Tc [(Ok)22.5(ud)19.5(a)-237.3(e)0(t)-230.9(a)13.3(l.)-224.3(\()]TJ 0 0 0 0.7 k 5.2993 0 TD [(10)21.1(8)]TJ 0 0 0 1 k 1.4084 0 TD [(\))-235.9(c)0(o)20.8(m)0(p)19.1(a)0(r)19.2(e)0(d)-227.7(t)0(h)21.4(e)-234.5(ef)80.4(fe)20.7(ct)19.8(s)-238.7(o)0(f)-223.5(a)0(n)17.2(t)0(i)24.9(-)0(T)19.1(N)0(F)]TJ /F17 1 Tf 13.5108 0 TD (a)Tj /F11 1 Tf 0.8593 0 TD [(\(e)19(ta)16.9(ne)20.1(r)11.9(c)0(e)20.4(p)0(t)22.3(,)]TJ -21.0778 -1.2114 TD (in)Tj /F12 1 Tf 0.7818 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ix)17.8(im)21.7(ab)-244.6(a)13.3(n)0(d)-240(a)0(d)14.1(a)13.3(li)20.7(m)12.3(u)0(m)19.1(a)0(b)18(\))-253.8(a)13.3(n)0(d)-245.9(a)13.3(nt)19.5(i-)17.2(IL)22.6(-)13.8(6)-255(\(T)20.1(CZ)19.7(\))-253.8(t)15.6(he)16(r)11.9(a)0(p)20.1(y)-252.2(ag)17.8(a)13.3(i)0(n)19.2(s)11.9(t)]TJ -1.3009 -1.2114 TD [(A)12.7(A)-434.9(a)13.3(m)0(y)16.8(l)0(o)21.9(i)0(d)22.1(o)0(s)22.6(i)0(s)-420.3(b)0(y)-420.5(m)12.3(ea)17.5(s)11.9(u)0(r)18.7(i)0(n)19.2(g)-431.2(SA)21.1(A)-428.9(l)0(e)21.5(v)0(e)20.6(l)0(s)17.2(.)-432.5(A)12.7(l)0(o)21.9(n)0(g)-421.3(w)0(i)23.9(t)0(h)-420.2(a)-428.3(mo)17(r)11.9(e)]TJ T* [(im)15.7(p)12.7(o)0(s)16.6(i)0(n)19.2(g)-431.2(im)15.7(p)12.7(r)0(o)16.6(v)0(e)20.6(m)0(e)16.6(n)0(t)-422.1(i)0(n)-422.4(e)0(G)20(F)0(R)-423.6(a)0(n)17.2(d)-428.9(am)19.7(yl)15.7(oi)20(d)-434.8(r)11.9(eg)20.6(re)16.1(ss)17.8(io)20(n,)-422.6(SA)15.2(A)]TJ 0 -1.2055 TD [(co)20.8(nc)20.1(en)20.1(tr)21.5(at)16.9(io)20(n)-258.7(d)0(e)17(c)0(r)22.1(e)0(a)17.5(s)11.9(ed)-251.6(mo)17(r)11.9(e)-264.3(s)11.9(i)0(g)19.8(n)0(i)]TJ /F12 1 Tf 13.8867 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(ca)17.5(nt)19.5(ly)-252.8(i)15.3(n)-264.6(th)21.4(e)-264.3(a)13.3(nt)19.5(i-)17.2(IL)22.6(-6)-253.1(gr)22.3(ou)17.4(p)]TJ -14.4059 -1.2114 TD [(th)21.4(an)-388.6(a)13.3(n)0(t)19.5(i)0(-)23.2(T)0(N)16.2(F)]TJ /F17 1 Tf 5.8602 0 TD (a)Tj /F11 1 Tf 1.0205 0 TD [(gr)16.4(ou)23.4(p.)-383.9(Ta)18.6(k)11.6(e)0(n)-385.7(a)0(l)18.6(l)-394.5(to)20.2(ge)20.6(th)21.4(er)16.1(,)-390.7(S)0(A)15.2(A)-393.1(s)11.9(e)0(e)20.4(m)0(s)-387.5(t)0(o)-385.6(b)0(e)-385(a)]TJ -6.8807 -1.2114 TD [(re)-7.7(lia)-7.8(ble)-463.2(mark)-10.6(er)-461.3(of)-456.2(re)-7.7(spon)-8.5(se)-461.3(to)-457.2(bio)-11.1(logi)-12(c)-455.3(ther)-10.2(apy)-464.8(in)-458.2(rhe)-7.9(uma)-9.4(tic)]TJ T* [(pa)20.1(ti)18.9(en)20.1(ts)-217.2(wi)18(th)-217.3(s)11.9(e)0(c)14.4(o)0(n)20.5(d)12.7(ar)19.2(y)-228.3(a)0(m)19.7(y)0(l)21.7(o)0(i)20(d)0(o)17.4(s)11.9(is)21.3(.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 45.3543 428.655 Tm [(SAA)-301.8(IN)-302.3(COVID-19)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 408.6424 Tm [(Si)17.8(nc)20.1(e)-228.5(w)14.6(e)-228.5(a)0(r)19.2(e)-228.5(cu)22.9(rr)17.8(en)20.1(tl)20.9(y)-228.3(e)0(x)18.7(p)12.7(er)16.1(i)15.3(e)0(n)14.1(c)0(i)25.5(n)0(g)-218.4(a)-231.4(p)12.7(a)0(n)17.2(d)12.8(em)16.6(i)15.3(c)-228.5(of)-217.5(CO)16.5(VI)21.5(D)12.9(-)0(1)21.4(9)0(,)-222(w)14.6(e)]TJ T* [(s)11.9(u)0(m)19.1(m)0(a)19.7(r)11.9(iz)19.6(ed)-191.9(6)-195.3(a)13.3(rt)21.5(ic)19.6(le)15.5(s)-191(r)0(e)16.1(p)12.7(or)16.6(ti)24.9(ng)-188.6(on)-188.3(S)14.5(A)0(A)-189.5(a)13.3(s)-197(a)-195.6(bi)20(om)17(a)13.3(r)0(k)17.5(e)0(r)-186.8(i)0(n)-183.7(p)0(a)20.1(t)0(i)18.9(e)0(n)20.1(t)0(s)]TJ 0 -1.2055 TD [(with)-438(COVI)14.1(D-19)-435.6(foun)14(d)-446.8(i)0(n)-440.3(our)-442.1(res)10.1(earc)9.8(h)-441.7(throug)13.4(h)-441.7(PubMe)12.5(d)-446.8(and)]TJ 0 -1.2114 TD [(Sc)12.7(op)17.4(us)-428.9(da)14.1(ta)16.9(ba)18(se)16.1(s)-435.7(\()]TJ /F14 1 Tf 0 0 0 rg 7.6684 0 TD [(Ta)12.8(bl)13.3(e)-432.3(9)]TJ /F11 1 Tf 0 0 0 1 k 3.2166 0 TD [(\).)-429.6(Al)18(l)-436.3(o)0(f)-426.4(t)0(h)15.4(e)-431.4(ar)13.3(ti)13(cl)15.5(es)-425.5(we)18.8(re)-431.4(pu)13.6(bl)21.9(is)15.3(hed)]TJ -10.885 -1.2114 TD [(in)-219.5(20)21.1(20)21.1(.)]TJ 1.2651 -1.2114 TD [(In)-188.2(cr)22.1(it)18.9(ic)19.6(a)13.3(l)0(l)22.6(y)-198.4(il)20.6(l)-197.6(C)0(O)16.5(V)0(I)21.5(D)12.9(-1)15.4(9)-195.3(p)12.7(at)16.9(ie)19.6(nt)19.5(s)-197(a)-195.6(cy)20.6(to)20.2(ki)20.9(ne)-188.8(st)15.5(or)22.6(m)-196.5(w)0(i)18(t)0(h)-187.5(h)11.8(ig)19.8(h)11.8(l)0(y)]TJ -1.2651 -1.2114 TD [(el)21.5(ev)20.6(at)16.9(ed)-144.1(IL)16.6(-)13.8(6)-159.5(h)11.8(a)0(s)-147.9(b)0(e)20.9(e)0(n)-147(d)0(e)17(s)11.9(cr)16.1(ib)20(ed)-144.1(\()]TJ 0 0 0 0.7 k 12.7827 0 TD [(19)21.1(3)]TJ 0 0 0 1 k 1.4084 0 TD [(\).)-149.2(S)14.5(i)0(n)19.2(c)0(e)-146.7(S)0(A)15.2(A)-154.4(is)-151.8(co)20.8(r)11.9(r)11.9(e)0(l)15.5(a)13.3(te)19.8(d)-160.3(w)14.6(it)18.9(h)]TJ -14.1911 -1.2114 TD [(IL)22.6(-6)-336.7(an)17.2(d)-345.3(i)0(n)19.2(v)0(o)21.1(l)0(v)21.7(e)0(d)-335.1(i)0(n)-338.8(t)0(h)21.4(e)-347.9(p)12.7(a)0(t)16.9(h)11.8(og)21.1(en)20.1(es)22.1(is)-336.8(of)-336.9(th)21.4(e)-347.9(r)11.9(is)15.3(k)-346.5(c)0(o)20.8(n)0(d)22.6(i)0(t)18.9(i)0(o)20(n)0(s)-336.3(f)0(o)21.2(r)]TJ 0 -1.2055 TD [(s)11.9(e)0(v)20.6(e)0(r)16.1(e)-330(CO)22.4(VI)15.5(D)12.9(-)0(1)21.4(9)-332.6(\(o)19.5(be)20.9(s)11.9(i)0(t)18.9(y)0(,)-320.6(d)12.7(ia)16.7(be)20.8(te)19.8(s)-328.2(a)0(n)17.2(d)-327.4(at)16.9(h)11.8(e)0(r)22.1(o)0(g)15.1(e)0(n)20.1(e)0(s)22.1(i)0(s)21.3(\))0(,)-322.2(i)0(t)-321.2(m)12.3(ig)19.8(h)11.8(t)]TJ 0 -1.2114 TD [(al)18.6(s)11.9(o)-335.5(pl)18.1(ay)-328.4(a)-338.8(r)11.9(ol)21.9(e)-341.9(i)15.3(n)-342.2(t)0(h)21.4(e)-335.9(pa)20.1(th)21.4(og)21.1(en)14.1(es)22.1(is)-324.9(of)-330.9(CO)22.4(VI)21.5(D-)20.8(19)-331(a)13.3(n)0(d)-329.5(t)0(h)21.4(e)0(r)16.1(e)0(f)20.7(o)0(r)22.6(e)]TJ T* [(pr)18.7(es)22.1(en)20.1(t)-229.1(a)-231.4(po)17.4(t)15.6(e)0(n)14.1(t)15.6(ia)16.7(l)-227.4(b)0(i)20(o)0(m)23(a)0(r)19.2(k)0(e)15.8(r)-226.8(an)17.2(d)-226(t)0(h)15.4(e)0(r)22.1(a)0(p)20.1(e)0(u)17(t)15.5(ic)-225.1(t)15.6(a)0(r)19.2(g)0(e)20.6(t)0(.)]TJ 1.2651 -1.2114 TD [(SAA)-401.8(is)-402.4(increased)-401.6(in)-404.5(all)-399.8(COVID-19)-403.6(patients)-402.8(with)-402.2(the)-404(mean)]TJ -1.2651 -1.2114 TD [(SAA)-258.6(value)-264.3(4)-255(times)-262.9(higher)-256.7(in)-261.2(critically)-263.1(ill)-254.5(than)-259.8(in)-261.2(mild-ill)-260.6(patients)]TJ T* (\()Tj 0 0 0 0.7 k 0.3521 0 TD [(10)-14.7(9)]TJ 0 0 0 1 k 1.4561 0 TD [(\))-9.1(.)-516(Mo)-11.4(r)-12(e)-7.7(ov)-8.8(e)-7.7(r)-12(,)-516(S)0(h)-9.5(i)-515.8(e)-7.7(t)-515.6(al)-11.2(.)-516(\()]TJ 0 0 0 0.7 k 10.5926 0 TD 0.0103 Tc [(11)10.3(0)]TJ 0 0 0 1 k 1.4561 0 TD 0.0074 Tc [(\))-508.9(r)7.4(e)-6.3(p)-3.7(or)7.4(t)-6.9(e)-0.3(d)-505(S)-2(A)7.4(A)-516.3(levels)-505.8(wer)7.4(e)]TJ -13.8569 -1.2055 TD 0 Tc [(increased)-395.6(whereas)-399.5(CRP)-388(levels)-394.2(were)-394.7(normal)-396.1(in)-392.5(more)-390.6(than)-397(20%)]TJ 0 -1.2114 TD [(of)-229.5(patients.)-232.6(While)-236.6(in)-225.4(patients)-235.7(with)-229.2(both)-231.8(SAA)-228.8(and)-232.6(CRP)-232.8(within)-233.8(the)]TJ T* [(reference)-346.4(range)-350.1(no)-343.5(severe)-346.9(pneumonia)-346.5(occurred,)-347.9(in)-344.8(some)-342.8(of)-348.8(the)]TJ T* [(patients)-331.2(with)-330.6(normal)-330.5(CRP)-328.3(but)-331(elevated)-335.8(SAA)-330.2(severe)-329(pneumonia)]TJ T* [(was)-443.6(found,)-441.6(suggesting)-448.1(higher)-441.7(sensitivity)-443(of)-444.3(SAA)-443.6(for)-438.4(assessing)]TJ T* [(COVID-19)-254.4(severity.)-253(Wang)-251.6(and)-256.5(co-workers)-252.6(\()]TJ 0 0 0 0.7 k 17.6822 0 TD (111)Tj 0 0 0 1 k 1.4382 0 TD [(\))-247.8(validated)-255.1(more)]TJ -19.1204 -1.2114 TD (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cant)-422.5(correlation)-430.1(between)-426(disease)-427.6(severity)-429.2(and)-423.6(SAA)-425.7(level)]TJ -2.4169 -1.2055 TD [(than)-283.7(CRP)-280.6(or)-281.8(ESR.)-280.4(In)-283.7(addition,)-285.2(they)-280.2(found)-283.6(SAA)-282.5(value)-288.2(above)-279(100)]TJ 0 -1.2114 TD [(mg/L)-431.2(as)-422.4(an)-430.4(indicator)-428.2(of)-432.4(disease)-427.6(progress)-433.5(to)-421.4(the)-427.9(critical)-434(stage.)]TJ T* [(Huan)-230.5(Li)-229.5(et)-230.9(al.)-228.9(\()]TJ 0 0 0 0.7 k 5.9378 0 TD (112)Tj 0 0 0 1 k 1.4382 0 TD [(\))-223.9(reported)-238.3(SAA)-228.8(and)-232.6(SAA)-228.8(to)-230.4(lymphocyte)-230.5(count)]TJ -7.376 -1.2114 TD [(ratio)-249.6(as)-243.3(sensitive)-253.3(indicators)-249.2(of)-241.4(COVID-19)-248.5(severity)-250.2(and)-250.5(prognosis)]TJ T* [(\(more)-399.6(sensitive)-396.5(than)-397(CRP)-393.9(or)-395.2(PCT\).)-393.9(The)-396.4(initial)-399.3(SAA)-395.9(level)-394.2(was)]TJ T* [(correlated)-407.2(with)-402.2(future)-403.7(dynamic)-405.2(changes)-405.7(of)-402.5(CT)-400.9(scans)-408.3(meaning)]TJ 0 -1.2055 TD [(that)-200.4(patients)-205.9(with)-205.3(higher)-203(initial)-202.4(SAA)-204.9(levels)-203.2(are)-203.3(more)-199.6(likely)-204.4(to)-200.6(have)]TJ 0 -1.2114 TD [(worsening)-348.8(of)-342.9(CT)-341.3(scans.)-351.4(Interestingly,)-344.9(initial)-345.6(SAA)-348.1(was)-342.1(found)-349.3(to)]TJ T* [(have)-348.1(a)-350.7(higher)-352.2(predictive)-352.8(value)-353.8(for)-348.9(disease)-356(progression)-349.9(than)-355.3(the)]TJ 27.4512 66.8735 TD [(initial)-297.9(CT)-299.5(scan.)-297.7(A)-297.7(retrospective)-302.8(study)-300.7(of)-295.1(COVID-19)-302.2(death)-300.4(cases)]TJ 0 -1.2114 TD [(revealed)-267.8(that,)-262.9(among)-265.7(included)-268.9(serum)-269.1(biomarkers,)-271(only)-262.1(SAA)-264.6(was)]TJ T* (signi)Tj /F12 1 Tf 1.8858 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cantly)-418.7(elevated)-419.3(in)-410.4(all)-417.7(of)-414.5(the)-416(patients)-420.7(with)-414.2(fatal)-419.4(outcome)]TJ -2.4169 -1.2114 TD (\()Tj 0 0 0 0.7 k 0.3461 0 TD (113)Tj 0 0 0 1 k 1.4322 0 TD [(\).)-268.5(Mo)-268(et)-266.7(al.)-270.6(\()]TJ 0 0 0 0.7 k 4.983 0 TD (114)Tj 0 0 0 1 k 1.4382 0 TD [(\))-265.7(showed)-268.3(by)-265.4(logistic)-269.3(regression)-273.6(analysis)-266.7(that)]TJ -8.1996 -1.2114 TD [(SAA,)-243.5(but)-247.5(not)-244.4(CRP,)-241.6(can)-247.1(serve)-243.7(as)-249.3(an)-239.4(independent)-252.6(predictive)-251.4(factor)]TJ T* [(of)-354.8(COVID-19)-355.9(course.)-358.9(At)-359.7(the)-350.3(cut-of)55.6(f)-353.5(value)-353.8(of)-360.8(122.9)-354.5(mg/L,)-356.4(SAA)]TJ 0 -1.2055 TD [(can)-300.8(predict)-305.2(acute)-302(exacerbation)-308(with)-300.8(an)-299.1(accuracy)-301.6(of)-301.1(89.1%.)]TJ 1.2651 -1.2114 TD [(To)-366(conclude,)-374.4(SAA)-366(might)-370.2(give)-371.4(additional)-371.2(information)-371.9(about)]TJ -1.2651 -1.2114 TD [(C)-6.4(O)-7(VI)-8.4(D-)-9.1(19)-516(se)-13.7(v)-7.5(e)0(r)-7.7(i)-8.5(ty)-511.1(a)-10.6(n)0(d)-514.5(p)0(r)-11.2(o)-7.3(gn)-9.5(o)-7.3(s)0(i)-8.6(s)-513.2(to)-510.9(mo)-12.8(re)-515(c)-7.7(o)-7.3(mm)-11.1(on)-9.3(l)-6.6(y)-508.8(us)-11.2(e)-7.7(d)]TJ T* [(biomarkers.)-420.1(Therefore,)-423.4(SAA)-413.8(measurement)-424.5(should)-418.2(be)-414.8(included)]TJ T* [(in)-237.4(managing)-239.3(COVID-19)-236.5(patients.)-238.5(At)-240.3(the)-237(present)-239.9(moment,)-236.2(to)-236.4(our)]TJ T* [(knowledge,)-205.6(there)-208.9(are)-203.3(no)-206.2(published)-206.9(data)-201.7(on)-206.2(SAA)-204.9(as)-201.6(a)-207.5(biomarker)-202.5(of)]TJ 0 -1.2055 TD [(COVID-19)-206.7(severity)-202.5(in)-201.6(patients)-205.9(with)-205.3(IRD,)-200.7(so)-204.2(future)-206.8(studies)-208(should)]TJ 0 -1.2114 TD [(explore)-294.5(the)-296.6(clinical)-291.1(relevance)-296.3(of)-295.1(SAA)-294.4(as)-291.1(a)-297(biomarker)-292(in)-297(the)-290.7(new)]TJ T* [(era)-298.8(of)-301.1(coexistence)-306.9(of)-301.1(IRD)-299.3(patients)-307.3(and)-298.3(SARS-CoV-2.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 514.2046 Tm [(LIMITATIONS)-303(OF)-305.3(SAA)-297.1(AS)-303.2(A)]TJ 0 -1.1669 TD [(BIOMARKER)-304.2(OF)-300.6(INFLAMMATORY)]TJ T* [(RHEUMATIC)-305.9(DISEASES)]TJ /F11 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[(rapid)-532.9(p)3.8(r)6.5(o)-1.1(gr)6.5(es)6.5(sio)6.5(n)-527(of)-527.6(se)5.6(co)6.5(ndar)6.5(y)-534.4(a)3.9(my)9.8(lo)6.5(idos)6.5(is.)]TJ /F16 1 Tf 20.4551 0 TD 0.0334 Tc [(Br)-532.4(Med)-532.4(J)]TJ /F11 1 Tf 4.8152 0 TD 0.035 Tc [(\(19)7.5(83\))-529.1(28)7.5(6)]TJ -25.2702 -1.2699 TD 0 Tc (\(6375\):1391)Tj /F13 1 Tf 4.7396 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(3.)-300.8(doi:)-301.1(10.1136/bmj.286.6375.1391)]TJ -6.448 -1.2624 TD [(7.)-497.3(Danesh)-285.3(J,)-276.4(Whincup)-280.5(P,)-285.8(Walker)-281(M,)-272.8(Lennon)-286.2(L,)-279(Thomson)-280.4(A,)-281.8(Appleby)-277.4(P,)-278.3(et)-279.8(al.)]TJ 1.1943 -1.2699 TD [(Low)-264.9(grade)-269.3(in)]TJ /F12 1 Tf 5.2385 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammation)-268.1(and)-270.8(coronary)-267.6(heart)-263.1(disease:)-270.5(Prospective)-267.4(study)-270(and)]TJ -5.7676 -1.2624 TD 0.0171 Tc [(u)-7.2(p)0.4(d)-7.2(a)0.5(t)-5.9(e)2.2(d)-528.7(m)-2.4(et)-5.9(a-)-6.9(an)-8.8(al)-5(yses.)]TJ /F16 1 Tf 10.4997 0 TD 0.0239 Tc [(Br)-511.6(Med)-511.7(J)]TJ /F11 1 Tf 4.7018 0 TD 0.0202 Tc [(\(2000\))-521.2(3)7.9(21:199)]TJ /F13 1 Tf 6.4706 0 TD 0 Tc ()Tj /F11 1 Tf 0.5291 0 TD 0.0202 Tc [(204.)-517.7(do)6.2(i:)-525.3(10.1136/)]TJ -22.2012 -1.2699 TD 0 Tc (bmj.321.7255.199)Tj -1.1943 -1.2624 TD [(8.)-497.3(Gasparyan)-360.2(AY,)-359.8(Ayvazyan)-356.2(L,)-354.6(Blackmore)-359.1(H,)-352.4(Kitas)-359.7(GD.)-355.7(Writing)-354.4(a)-356.7(narrative)]TJ 1.1943 -1.2699 TD [(biomedical)-330.7(review:)-328(considerations)-337.8(for)-326.6(authors,)-324.3(peer)-332.5(reviewers,)-333(and)-323.7(editors.)]TJ /F16 1 Tf T* [(Rheumatol)-303(Int)]TJ /F11 1 Tf 6.0776 0 TD [(\(2011\))-308.2(31\(11\):1409)]TJ /F13 1 Tf 7.6499 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(17.)-305.6(doi:)-301.1(10.1007/s00296-011-1999-3)]TJ -15.4282 -1.2624 TD [(9.)-497.3(De)-381.9(Beer)-382.9(FC,)-382.4(Mallya)-382.2(RK,)-376.7(Fagan)-381.2(EA,)-385(Lanham)-384.7(JG,)-377.2(Hughes)-382.8(GR,)-380(Pepys)-386.2(MB.)]TJ 1.1943 -1.2699 TD [(Serum)-375.6(amyloid-A)-370.8(protein)-377.6(concentration)-375.2(in)-370.7(in)]TJ /F12 1 Tf 18.7694 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-375.6(diseases)-374(and)-369.1(its)]TJ -19.2985 -1.2624 TD [(relationship)-236.4(to)-233.6(the)-232.6(incidence)-235.4(of)-229.5(reactive)-234.3(systemic)-236.4(amyloidosis.)]TJ /F16 1 Tf 24.6504 0 TD (Lancet)Tj /F11 1 Tf 2.8574 0 TD (\(1982\))Tj -27.5077 -1.2699 TD (2\(8292\):231)Tj /F13 1 Tf 4.7396 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(4.)-300.8(doi:)-301.1(10.1016/s0140-6736\(82\)90321-x)]TJ -7.0527 -1.2624 TD [(10.)-502.1(Maury)-216(CPJ,)-214.9(Teppo)-211.7(AM,)-213.2(Wegelius)-218.2(O.)-214.7(Relationship)-213.2(between)-216.7(urinary)-215.7(sialylated)]TJ 1.6781 -1.2699 TD [(saccharides,)-253.5(serum)-245.3(amyloid)-247.7(A)-250.3(protein)-249.1(and)-248.2(C-reactive)-244.8(protein)-249.1(in)-249.7(rheumatoid)]TJ T* [(arthrit)-10.1(is)-502.3(and)-505.2(system)-12.8(ic)-503.2(lupus)-509.5(erythemato)-12.6(sus.)]TJ /F16 1 Tf 18.8147 0 TD [(Ann)-504.4(Rheum)-508.4(Dis)]TJ /F11 1 Tf 7.3399 0 TD [(\(1)-9.5(982\))-502.8(41)]TJ -26.1547 -1.2624 TD (\(3\):268)Tj /F13 1 Tf 2.8271 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(71.)-305.6(doi:)-301.1(10.1136/ard.41.3.268)]TJ -5.0117 -1.2699 TD [(11.)-502.1(Shen)-349.5(C,)-350.6(Sun)-353.2(XG,)-349(Liu)-352(N,)-350.7(Mu)-348.7(Y,)-351.3(Hong)-348.9(CC,)-344.7(Wei)-351.6(W,)-348.5(et)-355.4(al.)-349.8(Increased)-350.5(serum)]TJ 1.6781 -1.2624 TD [(amyloid)-225.1(A)-220.1(and)-217.9(its)-223(association)-222.5(with)-218(autoantibodies,)-219.7(acute)-222.1(phase)-226.5(reactants)-223.2(and)]TJ 0 -1.2699 TD [(disease)-337.3(activity)-334.7(in)-340.4(patients)-335.2(with)-331.4(rheumatoid)-342.1(arthritis.)]TJ /F16 1 Tf 21.8006 0 TD [(Mol)-338(Med)-331.4(Rep)]TJ /F11 1 Tf 5.8281 0 TD (\(2014\))Tj -27.6287 -1.2624 TD (11:1528)Tj /F13 1 Tf 3.0993 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(34.)-298(doi:)-308.6(10.3892/mmr.2014.2804)]TJ -5.2838 -1.2699 TD [(12.)-502.1(Kumon)-211.4(Y,)-207.7(Suehiro)-206.5(T,)-211.2(Hashimoto)-205.5(K,)-212.1(Nakatani)-205.6(K,)-212.1(Sipe)-210.7(JD.)-205(Local)-209.3(expression)-209.1(of)]TJ 1.6781 -1.2699 TD [(acute)-252.3(phase)-241.6(serum)-252.8(amyloid)-247.7(A)-242.8(mRNA)-247.2(in)-242.2(rheumatoid)-251.4(arthritis)-247.8(synovial)-247(tissue)]TJ 0 -1.2624 TD [(and)-301.1(cells.)]TJ /F16 1 Tf 4.0215 0 TD [(J)-300.3(Rheumatol)]TJ /F11 1 Tf 5.2234 0 TD [(\(1999\))-300.7(26:785)]TJ /F13 1 Tf 5.5182 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (90.)Tj -16.9476 -1.2699 TD 0.0155 Tc [(13.)-492.2(T)2.1(arg)4.8(o)1.5(n)4.7(s)1.5(ka)6.5(-St)7.6(e)0.6(pn)4.7(iak)-508.4(B)1.3(,)-507.3(M)1(aj)15.5(d)-8.2(a)-1.1(n)-509.3(M)1(.)-507.3(S)-0.3(eru)6.4(m)-510.5(amy)4.8(l)0.9(oid)-507.7(A)-514.5(a)6.5(s)-512.5(a)-515.1(m)3.6(a)6.5(r)1.5(ker)-504.9(o)1.5(f)]TJ 1.7159 -1.2624 TD 0.0128 Tc [(pe)12.8(r)-8.5(s)-1.2(istent)-509.1(in)]TJ /F12 1 Tf 5.3065 0 TD 0 Tc ()Tj /F11 1 Tf 0.5443 0 TD 0.0133 Tc [(ammat)5.4(i)1.2(on)-511.5(and)-517.4(a)4.3(n)-511.5(i)1.2(ndicator)-507.1(of)-504.5(cardio)13.3(vasc)13.3(u)-10.7(l)13.3(a)-10.3(r)-507.1(and)-509.9(r)-0.7(e)13.3(n)-4.8(al)]TJ -5.8508 -1.2699 TD 0 Tc [(i)-12.1(n)0(v)-13.9(o)0(l)-13.5(v)-10.7(em)-19.3(en)-10.6(t)-514.4(i)-12.1(n)-517.3(p)-9.1(a)-9(t)0(i)-12.5(e)0(n)-18.1(t)-7.9(s)-512.9(w)-10.9(it)-12.5(h)-512.2(r)-14(he)-13(u)-9.1(m)-11.9(at)-9.3(o)-14(i)0(d)-520.2(a)-9(rt)-14.3(hr)-19.6(it)-12.5(i)-12.1(s)0(.)]TJ /F16 1 Tf 22.1408 0 TD [(M)-9.4(e)0(d)-12.1(i)-9.7(a)-9.9(t)-7.9(or)-14.6(s)-513.6(I)0(n)]TJ /F22 1 Tf 5.4577 0 TD ()Tj /F16 1 Tf 0.5216 0 TD 0.0113 Tc (amm)Tj /F11 1 Tf -28.12 -1.2624 TD 0 Tc [(\(2014\))-308.2(2014:793628.)-299.7(doi:)-301.1(10.1155/2014/793628)]TJ -1.7159 -1.2699 TD [(14.)-502.1(Chambers)-289.1(RE,)-284.1(MacFarlane)-286(DG,)-280.1(Whicher)-286(JT,)-289.8(Dieppe)-283.6(PA.)-286.7(Serum)-284.9(amyloid-A)]TJ 1.6781 -1.2699 TD [(protein)-430.6(concentration)-428.1(in)-423.6(rheumatoid)-432.8(arthritis)-429.2(and)-422(its)-427.1(role)-427.8(in)-423.6(monitoring)]TJ 7.4999 0 0 7.4999 62.4189 147.7984 Tm 0.0319 Tc [(disease)-527.2(a)0.2(ctivity.)]TJ /F16 1 Tf 7.4533 0 TD 0.032 Tc [(Ann)-525.5(R)-2.4(heum)-532.5(Dis)]TJ /F11 1 Tf 7.7708 0 TD 0.0348 Tc [(\(1)7.3(98)7.3(3\))-521.7(42)7.3(\(6)7.3(\):66)7.3(5)]TJ /F13 1 Tf 7.3853 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.034 Tc [(7.)-526.6(do)4.9(i:)-526.6(10)6.5(.11)6.5(3)-1(6)6.5(/)]TJ -23.1461 -1.2699 TD 0 Tc (ard.42.6.665)Tj -1.6781 -1.2624 TD [(15.)-502.1(Cunnane)-286.3(G,)-283.5(Grehan)-283.6(S,)-281.6(Geoghegan)-282.1(S,)-281.6(McCormack)-286.1(C,)-275(Shields)-282.7(D,)-285.1(Whitehead)]TJ 1.6781 -1.2699 TD [(AS,)-229.5(et)-226.9(al.)-221.3(Serum)-232(amyloid)-225.1(A)-227.7(i)0(n)-227(the)-225(assessment)-231(of)-221.9(early)-229.3(in)]TJ /F12 1 Tf 21.9442 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-224.5(arthritis.)]TJ /F16 1 Tf -22.4734 -1.2624 TD [(J)-300.3(Rheumatol)]TJ /F11 1 Tf 5.2234 0 TD [(\(2000\))-308.2(27\(1\):58)]TJ /F13 1 Tf 6.2061 0 TD ()Tj /F11 1 Tf 0.514 0 TD (63.)Tj -13.6216 -1.2699 TD [(16.)-502.1(Yoo)-227(J,)-231(Lee)-224.4(SK,)-227.8(Lim)-226.3(M,)-227.4(Sheen)-228.3(D,)-224.7(Choi)-230(EH,)-221.3(Kim)-227.4(SA.)-229.5(Exosomal)-226.7(amyloid)-232.6(A)-227.7(and)]TJ 1.6781 -1.2699 TD 0.023 Tc [(lymphatic)-521(v)4.8(es)-6.1(sel)-520.7(e)0.6(nd)6.3(o)-6.1(t)0(helial)-520.7(hyaluronic)-521(acid)-515.3(r)-6.1(eceptor-1)-518.5(p)-1.3(roteins)-527.7(a)6.5(r)-6.1(e)]TJ 0 -1.2624 TD 0 Tc [(associated)-375.8(with)-369.2(disease)-375.1(activity)-372.5(in)-370.7(rheumatoid)-372.3(arthritis.)]TJ /F16 1 Tf 22.9269 0 TD [(Arthritis)-378.3(Res)-364.7(Ther)]TJ /F11 1 Tf -22.9269 -1.2699 TD [(\(2017\))-300.7(19:119.)-306(doi:)-301.1(10.1186/s13075-017-1334-9)]TJ 33.094 73.5581 TD [(17.)-502.1(Ostensen)-323.3(M,)-325.7(Marhaug)-321.4(G,)-321.3(Husby)-315.8(G.)-321.3(Amyloid-related)-325.2(serum)-320.9(protein)-324.7(\(SAA\))]TJ 1.6781 -1.2624 TD [(during)-315.3(and)-316.2(after)-321.7(pregnancy)-316.4(in)-310.2(healthy)-317.8(women)-312(and)-316.2(women)-319.5(with)-316.3(rheumatic)]TJ 0 -1.2699 TD 0.0228 Tc [(dis)8.8(e)0.4(as)8.8(e.)]TJ /F16 1 Tf 3.6737 0 TD 0.0214 Tc [(AP)6.5(MIS)-518.4(I)-0.9(mmu)8.1(nol)]TJ /F11 1 Tf 7.8162 0 TD 0.0205 Tc [(\(1985\))-513.4(93\(1\):1)]TJ /F13 1 Tf 6.1985 0 TD 0 Tc ()Tj /F11 1 Tf 0.5291 0 TD 0.02 Tc [(5.)-517.9(doi:)-517.9(10.1111)7.6(/)-5.7(j)5.4(.1699-0463.)]TJ -18.2176 -1.2699 TD 0 Tc (1985.tb02913.x)Tj -1.6781 -1.2624 TD [(18.)-502.1(Hwang)-483.2(YG,)-482.4(Balasubramani)-483.2(GK,)-486.8(Metes)-481.9(ID,)-481.3(Levesque)-481.1(MC,)-486(Bridges)-481.9(SLJr,)]TJ 1.6781 -1.2699 TD [(M)-14.5(o)-14(re)-21.3(l)-14.6(a)-9(n)-10.8(d)-523.2(L)-13.3(W)-14.7(.)-522.8(D)-11.8(i)-12.1(f)49.1(f)-11.4(e)-14.9(re)-21.3(n)-10.8(t)-15.5(i)-12.1(a)-9(l)-528.6(r)0(e)-21.3(s)-14(p)-9.1(o)-14(n)-10.8(s)-14(e)-521.3(o)-14(f)-525.4(s)-14(er)-21.3(u)-9.1(m)-526(a)-16.5(m)-11.9(y)-10.7(l)0(o)-21(i)-12.1(d)-523.2(A)-522.5(t)-15.5(o)-520.5(d)-16.7(i)-12.1(f)49.1(f)-11.4(er)-21.3(e)-14.9(n)-10.8(t)]TJ 0 -1.2624 TD [(therapies)-366.1(in)-363.1(early)-365.4(rheumatoid)-364.8(arthritis)-361.2(and)-361.5(its)-359.1(potential)-364.9(value)-368.1(as)-355.5(a)-364.3(disease)]TJ 0 -1.2699 TD [(activity)-433(biomarker.)]TJ /F16 1 Tf 8.1185 0 TD [(Arthritis)-438.8(Res)]TJ /F11 1 Tf 5.5635 0 TD [(\(2016\))-429.2(18:108.)-434.5(doi:)-429.6(10.1186/s13075-016-)]TJ -13.6821 -1.2624 TD (1009-y)Tj -1.6781 -1.2699 TD [(19.)-502.1(Wild)-458.7(N,)-456.6(Karl)-452.5(J,)-457.8(Grunert)-458.7(VP,)-458.1(Schmitt)-461.8(RI,)-452.6(Garczarek)-458.2(U,)-459(Krause)-460.7(F,)-456.3(et)-453.7(al.)]TJ 1.6781 -1.2699 TD [(D)-11.8(i)0(a)-13.6(g)0(n)-13.9(o)0(s)-12.9(i)0(s)-525(o)0(f)-516.7(r)0(h)-19.7(eum)-20.8(a)-9(t)-7.9(oi)-11(d)-515.6(a)-9(rt)-14.3(hr)-12.1(it)-12.5(i)-12.1(s)0(:)-521.6(m)0(u)-13.5(l)0(t)-14.9(i)0(v)-15.2(a)-9(ri)-11(a)-9(t)-7.9(e)-513.8(a)-9(na)-12.2(ly)-17.7(si)-11(s)-512.9(o)0(f)-524.3(b)0(i)-11(o)0(m)-18.4(a)-9(rk)-8.7(e)-14.9(r)0(s)-12.8(.)]TJ /F16 1 Tf 0 -1.2624 TD (Biomarkers)Tj /F11 1 Tf 4.8152 0 TD [(\(2008\))-300.7(13\(1\):88)]TJ /F13 1 Tf 6.2061 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(105.)-302.8(doi:)-301.1(10.1080/13547500701669410)]TJ -13.2058 -1.2699 TD [(20.)-502.1(De)-306.4(Seny)-301.6(D,)-307.8(Cobraiville)-305.4(G,)-306.1(Charlier)-305(E,)-308.5(Neuville)-304.2(S,)-304.2(Esser)-303.6(N,)-305.4(Malaise)-307.2(D,)-307.8(et)-302.5(al.)]TJ 1.6781 -1.2624 TD [(Acute-phase)-335.9(serum)-336(amyloid)-330.9(a)-334(i)0(n)-332.9(osteoarthritis:)-336.5(regulatory)-330.4(mechanism)-339.5(and)]TJ 0 -1.2699 TD (proin)Tj /F12 1 Tf 2.1922 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-481.5(properties.)]TJ /F16 1 Tf 9.3356 0 TD [(PloS)-482.7(One)]TJ /F11 1 Tf 4.3087 0 TD [(\(2013\))-482.1(8\(6\):e66769.)-491.1(doi:)-482.5(10.1371/)]TJ -16.3656 -1.2624 TD (journal.pone.0066769)Tj -1.6781 -1.2699 TD [(21.)-502.1(Ally)-426.2(MM,)-430.9(Hodkinson)-430.8(B,)-423.6(Meyer)-431.7(PW,)-429(Musenge)-429(E,)-421.9(Tikly)-431.1(M,)-423.9(Anderson)-436.1(R.)]TJ 1.6781 -1.2699 TD [(Serum)-269.8(matrix)-274.8(metalloproteinase-3)-274(in)-272.4(comparison)-267.4(with)-271(acute)-267.4(phase)-271.9(proteins)]TJ 0 -1.2624 TD [(as)-234.6(a)-235.8(marker)-239.9(of)-237(disease)-239.1(activity)-236.5(and)-233(radiographic)-247(damage)-238.4(in)-234.6(early)-236.9(rheumatoid)]TJ 0 -1.2699 TD (arthritis.)Tj /F16 1 Tf 3.6586 0 TD [(Mediators)-259.8(In)]TJ /F22 1 Tf 5.1175 0 TD ()Tj /F16 1 Tf 0.5216 0 TD (amm)Tj /F11 1 Tf 2.3055 0 TD [(\(2013\))-255.3(2013:183653.)-254.3(doi:)-255.7(10.1155/2013/183653)]TJ -13.2814 -1.2624 TD [(22.)-502.1(Targon)]TJ /F20 1 Tf 4.4901 0.0378 TD ()Tj /F11 1 Tf 0.1058 -0.0378 TD (ska-St)Tj /F23 1 Tf 2.4189 0 TD ()Tj /F11 1 Tf 0.4158 0 TD [(pniak)-376(B,)-370.7(Dryglewska)-377.2(M,)-378.6(Majdan)-376.9(M.)-371(In)]TJ /F12 1 Tf 16.0934 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(uence)-382(of)-373.1(long-term)]TJ -22.3751 -1.2699 TD (le)Tj /F12 1 Tf 0.6803 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(u)-9.1(n)0(o)-9.7(m)0(i)-8.9(d)-9.1(e)-506.2(t)-7.9(rea)-15.1(tme)-12(nt)-517.6(on)-508.6(se)-13.7(rum)-518.8(am)-13.4(ylo)-9(id)-520.2(con)-9.5(ce)-14.6(ntr)-10(a)-9(tio)-11.4(n)-509.7(i)0(n)-514.3(r)0(h)-12.1(eum)-13.3(a)-9(toi)-11.4(d)]TJ -1.2095 -1.2624 TD [(arthritis)-338.5(patients.)]TJ /F16 1 Tf 7.2114 0 TD [(Pharmacol)-336.5(Rep)]TJ /F11 1 Tf 6.4026 0 TD [(\(2010\))-330.9(62\(4\):719)]TJ /F13 1 Tf 6.7125 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(25.)-328.3(doi:)-331.3(10.1016/s1734-)]TJ -20.8406 -1.2699 TD (1140\(10\)70329-7)Tj -1.6781 -1.2699 TD [(23.)-502.1(Con)18.9(nol)21.1(ly)-221.8(M,)-227.4(Mu)14.1(ll)16.2(an)-223.9(RH,)-222.2(Mc)16(Cor)15.7(mic)21.5(k)-229.1(J)0(,)-223.5(M)0(a)14.3(tth)16.3(ews)-213.6(C,)-222.1(Sul)21(liv)15.5(an)-223.9(O,)-222.2(Ke)16.2(nne)16.4(dy)-223.9(A,)]TJ 1.6781 -1.2624 TD [(et)-378.1(al.)-364.9(Acut)20.1(e-p)20.1(has)16.7(e)-385.3(s)0(e)16.5(r)0(u)14.7(m)-382.3(amyl)21.9(oid)-367.9(A)-386.4(r)0(e)16.5(gul)18.6(ates)-363.2(tum)16.4(or)-375.7(nec)19.9(ros)18.5(is)-373.8(fac)17.7(tor)-376.1(alp)20.2(ha)]TJ 0 -1.2699 TD [(an)-12.2(d)-508(m)0(a)-13.4(tri)-11.3(x)-514.7(turn)-11.6(ov)-9.6(er)-512.6(a)-9(n)0(d)-518.9(pred)-16.8(icts)-525.1(dis)-12.5(ease)-521.3(pro)-14.4(gre)-9.2(ssi)-9.8(on)-516.2(in)-521.9(pa)-10.6(tien)-15.5(ts)-513.2(wit)-8.2(h)]TJ 0 -1.2624 TD 0.0424 Tc (in)Tj /F12 1 Tf 0.8769 0 TD 0 Tc ()Tj /F11 1 Tf 0.5745 0 TD 0.0378 Tc 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[(are)-423.3(associated)-428.7(with)-429.7(clinical)-428(response)-423(to)-422.6(golimumab)-432.4(plus)-424.8(methotrexate)-426(in)]TJ 0 -1.2699 TD [(p)-9.1(a)0(t)-9.3(i)0(e)-11.9(n)0(t)-11.2(s)-505.3(w)-10.9(ith)-517.1(ac)-8.7(t)-7.9(ive)-521.4(rh)-12.1(eum)-13.3(a)-9(toi)-11.4(d)-508(a)-9(rth)-12.5(ri)-11(t)-7.9(i)0(s)-517.4(des)-15.3(pit)-14.1(e)-513.8(m)0(e)-11.7(tho)-12.5(tre)-14.1(xa)-9.7(t)-7.9(e)-506.2(t)-7.9(h)0(e)-13(rap)-17(y.)]TJ /F16 1 Tf T* [(J)-300.3(Rheumatol)]TJ /F11 1 Tf 5.2234 0 TD [(\(2009\))-308.2(36\(7\):1371)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(9.)-300.8(doi:)-301.1(10.3899/jrheum.080755)]TJ -14.5816 -1.2624 TD [(33.)-502.1(Doyle)-315.4(MK,)-317.3(Rahman)-316.8(MU,)-314.8(Frederick)-316.9(B,)-317.7(Birbara)-313(CA,)-313.7(de)-318.8(Vries)-310.3(D,)-315.4(Toedter)-314.9(G,)]TJ 1.6781 -1.2699 TD [(et)-287.4(al.)-289.3(Ef)66.9(fects)-289.7(of)-282.4(subcutaneous)-292(and)-285.9(intravenous)-293.5(golimumab)-288.8(on)-281.8(in)]TJ /F12 1 Tf 25.5726 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (ammatory)Tj -26.1017 -1.2624 TD [(bio)-9.9(marke)-14.3(rs)-504.1(in)-506.7(pat)-10.9(ients)-513.2(wit)-8.3(h)-504.6(rheuma)-11.7(toid)-511.9(arthr)-12.7(iti)-9.5(s:)-506.5(resul)-13.6(ts)-505.7(of)-501.6(a)-507.9(phase)-513.7(1,)]TJ 0 -1.2699 TD [(ra)-15.4(nd)-12.4(om)-10.8(iz)-11.9(ed)-16.4(,)-507.7(o)0(p)-15.6(e)0(n)-10.6(-)-8.8(la)-8.4(be)-13.8(l)-505.9(t)-7.9(ri)-11(a)-9(l)0(.)]TJ /F16 1 Tf 12.6994 0 TD [(R)-11.7(h)0(e)-9.6(u)0(m)-10.8(a)-9.9(to)-8.6(l)-509.4(\()0(O)-13.2(x)0(f)-17.9(ord)-13.5(\))]TJ /F11 1 Tf 8.8518 0 TD [(\(2)-9.5(01)-9.6(3\))-516(5)-12.3(2)0(\()-9.5(7)0(\))-9.5(:)-8.8(12)-9.6(14)]TJ /F13 1 Tf 7.4609 0 TD ()Tj /F11 1 Tf 0.514 0 TD (9.)Tj -29.526 -1.2624 TD [(doi:)-301.1(10.1093/rheumatology/kes381)]TJ -1.6781 -1.2699 TD [(34.)-502.1(Kobayashi)-238.8(T,)-233.8(Yokoyama)-232.1(T,)-233.8(Ito)-225.6(S,)-236.2(Kobayashi)-238.8(D,)-232.2(Yamagata)-227.6(A,)-236.4(Okada)-235.3(M,)-235(et)-226.9(al.)]TJ 1.6781 -1.2699 TD [(Periodontal)-246.3(and)-240.6(serum)-245.3(protein)-241.6(pro)]TJ /F12 1 Tf 13.8937 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(les)-239.9(in)-242.2(patients)-244.5(with)-240.7(rheumatoid)-243.8(arthritis)]TJ -14.4229 -1.2624 TD [(treated)-508.5(wit)-8.2(h)-497(tumor)-510.5(necrosis)-509.2(factor)-509.5(inhibitor)-503.4(adalim)-12.8(umab.)]TJ /F16 1 Tf 24.8469 0 TD [(J)-496.8(Period)-13.5(ontol)]TJ /F11 1 Tf -24.8469 -1.2699 TD [(\(2014\))-300.7(85\(11\):1480)]TJ /F13 1 Tf 7.6423 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(8.)-300.8(doi:)-301.1(10.1902/jop.2014.140194)]TJ -9.8345 -1.2624 TD [(35.)-502.1(Hammer)-375.1(HB,)-374.1(Fagerhol)-371.6(MK,)-370.2(Wien)-370(TN,)-371.7(Kvien)-372.7(TK.)-369.1(The)-374.1(soluble)-374.8(biomarker)]TJ 1.6781 -1.2699 TD [(calprotectin)-416.2(\(an)-417.6(S100)-408.1(protein\))-420.2(is)-411.6(associated)-413.6(to)-415(ultrasonographic)-417.1(synovitis)]TJ 0 -1.2624 TD [(scores)-221.7(and)-210.4(is)-215.1(sensitive)-217.1(to)-218.5(change)-217.1(in)-211.9(patients)-221.8(with)-210.5(rheumatoid)-221.2(arthritis)-217.6(treated)]TJ 0 -1.2699 TD [(with)-233.2(adalimumab.)]TJ /F16 1 Tf 7.4382 0 TD [(Arthritis)-234.7(Res)-228.6(Ther)]TJ /F11 1 Tf 7.2492 0 TD [(\(2011\))-232.7(13\(5\):R178.)-235.4(doi:)-225.5(10.1186/ar3503)]TJ -16.3656 -1.2699 TD [(36.)-502.1(Gabay)-256.9(C,)-259.9(Burmester)-258.4(GR,)-251.5(Strand)-263.1(V,)-256.7(Msihid)-256.5(J,)-253.7(Zilberstein)-261.9(M,)-257.6(Kimura)-251.9(T,)-256.5(et)-257.1(al.)]TJ 1.6781 -1.2624 TD [(Sarilumab)-464.8(and)-459.8(adalimumab)-465.1(dif)65.6(ferential)-464.7(ef)64.5(fects)-463.6(on)-455.7(bone)-461.9(remodelling)-466.6(and)]TJ 0 -1.2699 TD [(cardio)-12.6(vascular)-510.9(risk)-503.5(biomarker)-15.5(s,)-499(and)-505.2(predic)-13.6(tions)-504.8(of)-501.6(treatm)-12.7(ent)-502.3(outcome)-11.2(s.)]TJ /F16 1 Tf 0 -1.2624 TD [(Arthritis)-302.7(Res)-304.2(Ther)]TJ /F11 1 Tf 7.4609 0 TD [(\(2020\))-308.2(22\(1\):70.)-300.3(doi:)-301.1(10.1186/s13075-020-02163-6)]TJ -9.139 -1.2699 TD [(37.)-502.1(Nissinen)-287(R,)-286.7(Leirisalo-Repo)-291.5(M,)-287.9(Peltomaa)-282.7(R,)-286.7(Palosuo)-291.3(T,)-279.2(Vaarala)-289.7(O.)-290.3(Cytokine)]TJ 1.6781 -1.2624 TD [(a)-9(n)0(d)-511.3(c)0(h)-13(e)0(m)-11.7(o)0(k)-8.8(ine)-521.6(rec)-13.5(ept)-16.8(or)-511.8(p)-9.1(r)0(o)]TJ /F12 1 Tf 12.1929 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(le)-520.8(of)-509.2(p)-9.1(eri)-10.7(p)-9.1(h)0(e)-13(ral)-513.7(bl)-13.5(ood)-521(mo)-10.8(no)-9.7(nuc)-12.1(le)-14.3(ar)-514.3(cel)-14.1(ls)]TJ -12.7296 -1.2699 TD 0.0208 Tc [(d)4.1(u)-3.5(r)6.8(i)1.1(ng)-511.4(tr)6.8(ea)4.3(t)5.3(m)1.3(ent)-508.7(w)2.4(it)5.3(h)-514(i)1.1(n)]TJ /F12 1 Tf 11.059 0 TD 0 Tc ()Tj /F11 1 Tf 0.5518 0 TD 0.0156 Tc [(ix)-7.7(ima)-8.5(b)-520(in)-524.4(pat)-7.4(i)3.5(e)-6.8(n)-2.8(ts)-519.9(with)-519.2(ac)-6.8(tive)-520.9(rh)-5.2(eu)-8.7(ma)-8.5(toid)]TJ -11.6109 -1.2699 TD 0 Tc (arthritis.)Tj /F16 1 Tf 3.6813 0 TD [(Ann)-277.6(Rheum)-274.1(Dis)]TJ /F11 1 Tf 6.6596 0 TD [(\(2004\))-278(63\(6\):681)]TJ /F13 1 Tf 6.6596 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(7.)-270.6(doi:)-278.4(10.1136/ard.2003.008599)]TJ -19.1927 -1.2624 TD [(38.)-502.1(Xu)-361.9(Y,)-366.5(Yamada)-360.4(T,)-362.3(Satoh)-362.3(T,)-362.3(Okuda)-364(Y.)-366.5(Measurement)-362.6(of)-365.5(serum)-358.7(amyloid)-368.7(A1)]TJ 1.6781 -1.2699 TD [(\(SAA1\),)-259.7(a)-258.4(major)-260(isotype)-264.1(of)-252.2(acute)-259.9(phase)-264.3(SAA.)]TJ /F16 1 Tf 18.1344 0 TD [(Clin)-255(Chem)-259.1(Lab)-262.3(Med)]TJ /F11 1 Tf 8.2773 0 TD [(\(2006\))-255.3(44)]TJ -26.4117 -1.2624 TD (\(1\):59)Tj /F13 1 Tf 2.3433 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(63.)-298(doi:)-301.1(10.1515/CCLM.2006.012)]TJ -4.5355 -1.2699 TD [(39.)-502.1(De)-208.1(Seny)-203.3(D,)-209.5(Fillet)-201.7(M,)-204.7(Ribbens)-206.6(C,)-206.9(Mare)]TJ /F20 1 Tf 16.3278 0.0454 TD ()Tj /F11 1 Tf 0.0454 -0.0454 TD [(e)-203.8(R)0(,)-203.6(Meuwis)-204(MA,)-205.6(Lutteri)-207.7(L.)-211(Monomeric)]TJ -14.695 -1.2624 TD [(calgranulins)-332.4(measured)-331.2(by)-319.5(SELDI-TOF)-328(mass)-328.5(spectrometry)-329.5(and)-323.7(calprotectin)]TJ 0 -1.2699 TD [(m)-11.9(e)-14.9(a)-9(s)-14(u)-16.7(r)-14(ed)-538(by)-531.1(E)-12.5(L)-13.3(I)-14.7(S)0(A)-538.2(a)-9(s)-528(b)0(i)-18.6(o)-14(m)-11.9(a)-16.5(r)-14(k)-9.9(e)-14.9(r)0(s)-534.4(i)-12.1(n)-524.8(a)-9(r)-14(t)-15.5(h)-13.3(r)-14(i)-12.1(t)-7.9(i)-12.1(s)-14(.)]TJ /F16 1 Tf 20.9691 0 TD 0.0154 Tc [(Cl)4.9(i)5.7(n)-511.9(C)5.4(h)3.8(em)]TJ /F11 1 Tf 5.1024 0 TD 0.0123 Tc [(\(2008\))-514(54)]TJ -26.0715 -1.2699 TD 0 Tc (\(6\):1066)Tj /F13 1 Tf 3.3033 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(75.)-298(doi:)-301.1(10.1373/clinchem.2007.099549)]TJ -5.4955 -1.2624 TD [(40.)-502.1(Li)-365.5(TW,)-361.9(Zheng)-363.7(BR,)-361.4(Huang)-368.1(ZX,)-365.7(Lin)-361.2(Q,)-358.3(Zhao)-365.5(LK,)-361.4(Liao)-365.9(ZT,)-358.9(et)-363(al.)-364.9(Screening)]TJ 1.6781 -1.2699 TD [(disease-associated)-238.2(proteins)-225.3(from)-232.7(sera)-225.6(of)-221.9(patients)-229.3(with)-233.2(rheumatoid)-228.7(arthritis:)-226.4(a)]TJ 0 -1.2624 TD [(comparative)-308.9(proteomic)-301.8(study.)]TJ /F16 1 Tf 12.3063 0 TD [(Chin)-301.5(Med)-301.2(J)-300.3(\(Engl\))]TJ /F11 1 Tf 7.6196 0 TD [(\(2010\))-300.7(123\(5\):537)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (43.)Tj -29.2766 -1.2699 TD [(41.)-502.1(Seok)-462.8(A,)-470.8(Lee)-458.7(HJ,)-468.8(Lee)-458.7(S,)-463(Lee)-466.3(J,)-465.4(Mun)-465.4(S,)-463(Park)-461.1(A,)-463.2(et)-468.8(al.)-463.2(Identi)]TJ /F12 1 Tf 26.9559 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(cation)-469.4(and)]TJ -25.8069 -1.2624 TD [(Validation)-482.6(of)-471.4(SAA4)-475.9(as)-476.5(a)-477.7(Rheumatoid)-477.6(Arthritis)-474(Prescreening)-483.3(Marker)-476.8(by)]TJ 0 -1.2699 TD [(Liquid)-354.6(Chromatography)-348.9(Tandem-mass)-361.1(Spectrometry.)]TJ /F16 1 Tf 22.1181 0 TD (Molecules)Tj /F11 1 Tf 4.2029 0 TD [(\(2017\))-346(22)]TJ -26.321 -1.2699 TD [(\(5\):805.)-303.1(doi:)-301.1(10.3390/molecules22050805)]TJ -1.6781 -1.2624 TD [(42.)-502.1(Nys)-222.9(G,)-223(Cobraiville)-222.2(G,)-215.4(Servais)-226.4(AC,)-222.9(Malaise)-216.5(MG,)-222.4(de)-220.5(Seny)-226(D,)-217.1(Fillet)-224.4(M.)-219.8(Targeted)]TJ 1.6781 -1.2699 TD [(proteomics)-255.3(reveals)-258.2(serum)-252.8(amyloid)-255.3(A)-257.9(variants)-253.7(and)-255.7(alarmins)-254.1(S100A8-S100A9)]TJ 0 -1.2624 TD [(as)-280(key)-284.9(plasma)-279.2(biomarkers)-286.4(of)-282.4(rheumatoid)-281.6(arthritis.)]TJ /F16 1 Tf 20.3266 0 TD (Talanta)Tj /F11 1 Tf 3.4167 0 TD [(\(2019\))-278(204:507)]TJ /F13 1 Tf 5.9793 0 TD ()Tj /F11 1 Tf -29.7226 -1.2699 TD [(17.)-305.6(doi:)-301.1(10.1016/j.talanta.2019.06.044)]TJ -1.6781 -1.2624 TD [(4)-12.3(3)0(.)-512.5(F)-9.1(i)-12.1(l)0(i)-11.6(p)-9.1(ow)-17.3(ic)-11.9(z-)-16.1(So)-14.7(sn)-17.2(ow)-17.3(sk)-16.3(a)-515.5(A)-8.4(M,)-522.2(Ro)-12.3(zt)-15.2(r)-14(o)0(p)-15.6(o)0(w)-9.8(i)-12.1(cz)-14.6(-)-8.8(D)0(e)-11.5(n)-10.8(i)-12.1(s)0(i)-11(e)0(w)-18.2(i)0(c)-11.9(z)-521.3(K,)-522(Ro)-12.3(s)-14(e)0(n)-10.6(t)-7.9(ha)-14.7(l)-521(C)0(J)-12.2(,)]TJ 1.7008 -1.2699 TD [(Ba)-15.6(um)-512.4(J.)-518.3(The)-517.8(am)-13.4(yl)-10.1(oid)-12.6(os)-12.9(is)-509.9(of)-516.7(ju)-8.6(v)-10.7(e)0(n)-10.6(ile)-517.8(rh)-12.1(eum)-13.3(a)-9(toi)-11.4(d)-508(a)-9(rth)-12.5(ri)-11(t)-7.9(i)0(s)]TJ /F13 1 Tf 24.7184 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(com)-10.6(p)-9.1(ara)-16.8(ti)-12.5(ve)]TJ -25.2324 -1.2699 TD [(studies)-368.3(in)-363.1(Polish)-367.7(and)-361.5(American)-368.1(children.)-369.4(I.)-363.7(Levels)-369.4(of)-365.5(serum)-366.2(SAA)-365.3(protein.)]TJ /F16 1 Tf 0 -1.2624 TD [(Arthritis)-302.7(Rheumatol)]TJ /F11 1 Tf 8.2924 0 TD [(\(1978\))-300.7(21\(6\):699)]TJ /F13 1 Tf 7.4999 0 0 7.4999 174.8976 246.444 Tm ()Tj /F11 1 Tf 0.514 0 TD [(703.)-295.2(doi:)-301.1(10.1002/art.1780210615)]TJ -17.1895 -1.2699 TD [(44.)-502.1(Scheinberg)-452.7(MA,)-439.9(Hubscher)-452.8(O,)-441.4(Morteo)-442.1(OG,)-444(Benson)-449(MD.)-443.3(Serum)-443.6(amyloid)]TJ 1.6781 -1.2624 TD [(protein)-339.8(levels)-340.5(in)-332.9(south)-338(american)-338.4(children)-337.9(with)-339(rheumatoid)-342.1(arthritis:)-339.7(A)-333.5(co-)]TJ 0 -1.2699 TD [(operative)-212.4(study.)]TJ /F16 1 Tf 6.4782 0 TD [(Ann)-209.6(Rheum)-206.1(Dis)]TJ /F11 1 Tf 6.4555 0 TD [(\(1980\))-210(39:228)]TJ /F13 1 Tf 5.4275 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(30.)-207.3(doi:)-210.4(10.1136/ard.39.3.228)]TJ -20.5458 -1.2624 TD [(45.)-502.1(Kutulculer)-402.1(N,)-396.1(Karaca)-402.7(NE,)-401(Azarsiz)-397.1(E,)-399.2(Aksu)-396.7(G,)-404.4(Gulez)-396.2(N.)-396.1(Immunoglobulin)]TJ 1.6781 -1.2699 TD [(light)-376(chain)-370(levels)-378.3(can)-367.3(be)-376.6(used)-372.1(to)-369.7(determine)-382.6(disease)-375.1(stage)-373.9(in)-370.7(children)-375.7(with)]TJ T* [(juvenile)-305.7(idiopathic)-302.7(arthritis.)]TJ /F16 1 Tf 11.4294 0 TD [(Clin)-307.9(Lab)-300.1(Sci)]TJ /F11 1 Tf 5.178 0 TD [(\(2011\))-300.7(24\(2\):93)]TJ /F13 1 Tf 6.2061 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (8.)Tj -24.9981 -1.2624 TD [(46.)-502.1(Cantarini)-283.9(L,)-271.5(Giani)-280.9(T,)-279.2(Fioravanti)-275(A,)-281.8(Iacoponi)-272.5(F,)-282.5(Simonini)-273.6(G,)-283.5(Pagnini)-274.6(I,)-280.5(et)-272.2(al.)]TJ 1.6781 -1.2699 TD [(Serum)-451.2(amyloid)-444.3(A)-446.9(circulating)-447.5(levels)-446.3(and)-444.7(disease)-443.2(activity)-448.1(in)-446.3(patients)-448.6(with)]TJ 0 -1.2624 TD [(juvenile)-230.1(idiopathic)-227.1(arthritis.)]TJ /F16 1 Tf 11.2027 0 TD [(Yonsei)-233.7(Med)-225.6(J)]TJ /F11 1 Tf 5.367 0 TD [(\(2012\))-225.1(53\(5\):1045)]TJ /F13 1 Tf 7.0829 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(8.)-225.2(doi:)-225.5(10.3349/)]TJ -24.1666 -1.2699 TD (ymj.2012.53.5.1045)Tj -1.6781 -1.2624 TD [(47.)-502.1(Dev)-369.9(S,)-372.3(Singh)-372.6(A.)-364.9(Study)-377.7(of)-365.5(role)-367.3(of)-373.1(serum)-373.8(amyloid)-368.7(A)-371.3(\(SAA\))-367.1(as)-370.7(a)-371.8(marker)-368.4(of)]TJ 1.6781 -1.2699 TD [(disease)-458.3(activity)-463.2(in)-453.8(juvenile)-456.9(idiopathic)-461.4(arthritis.)]TJ /F16 1 Tf 19.7445 0 TD [(J)-451.5(Family)-461.5(Med)-452.4(Prim)-459.5(Care)]TJ /F11 1 Tf -19.7445 -1.2699 TD [(\(2019\))-300.7(8\(6\):2129)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(33.)-305.6(doi:)-301.1(10.4103/jfmpc.jfmpc_339_19)]TJ -8.8744 -1.2624 TD [(48.)-502.1(Miyamae)-278.6(T,)-271.6(Malehorn)-271.3(DE,)-274.9(Lemster)-272.2(B,)-272.4(Mori)-273.8(M,)-272.8(Imagawa)-279.2(T,)-271.6(Yokota)-268.9(S,)-274(et)-272.2(al.)]TJ 1.6781 -1.2699 TD 0.03 Tc [(Se)7.6(r)8.5(u)-1.8(m)-518.6(p)5.7(ro)8.4(t)7(e)0(i)10.3(n)-525.1(p)5.7(r)8.5(o)]TJ /F12 1 Tf 8.2999 0 TD 0 Tc ()Tj /F11 1 Tf 0.5518 0 TD 0.0265 Tc [(le)-525.1(i)6.8(n)-528.6(s)5(y)0.7(stemic-ons)5(et)-518.1(juvenil)4.4(e)-525.1(idio)4.9(path)5.7(ic)-525.1(arth)5.7(ritis)]TJ -8.8518 -1.2624 TD 0 Tc [(dif)58.1(ferentiates)-434(response)-430.6(versus)-439.4(nonresponse)-436(to)-422.6(therapy.)]TJ /F16 1 Tf 22.806 0 TD [(Arthritis)-438.8(Res)-425.2(Ther)]TJ /F11 1 Tf -22.806 -1.2699 TD [(\(2005\))-300.7(7\(4\):R746)]TJ /F13 1 Tf 6.8259 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(55.)-305.6(doi:)-301.1(10.1186/ar1723)]TJ 25.7616 83.6042 TD [(49.)-502.1(Lange)-361(U,)-353.2(Boss)-358.5(B,)-355.5(Teichmann)-360.5(J,)-359.5(Klr)-359.2(HU,)-356.6(Neeck)-358.7(G.)-359(Serum)-352.9(amyloid)-361.1(A)]TJ /F13 1 Tf 30.418 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (an)Tj -29.2463 -1.2699 TD [(indicator)-338.3(of)-327.8(in)]TJ /F12 1 Tf 5.8583 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(ammation)-328.6(in)-332.9(ankylosing)-335.7(spondylitis.)]TJ /F16 1 Tf 15.0881 0 TD [(Rheumatol)-333.3(Int)]TJ /F11 1 Tf 6.138 0 TD (\(2000\))Tj -27.6211 -1.2624 TD (19:119)Tj /F13 1 Tf 2.6155 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(22.)-298(doi:)-301.1(10.1007/s002960050114)]TJ -4.8076 -1.2699 TD [(50.)-502.1(Jung)-268(SY,)-268.9(Park)-272.1(MC,)-266.8(Park)-272.1(YB,)-267.2(Lee)-269.8(SK.)-265.6(Serum)-269.8(amyloid)-270.4(A)-265.5(a)0(s)-272.4(a)-266(useful)-269.6(indicator)]TJ 1.6781 -1.2624 TD [(of)-448.7(disease)-458.3(activity)-448.1(in)-453.8(patients)-448.6(with)-452.4(ankylosing)-449.1(spondylitis.)]TJ /F16 1 Tf 24.6428 0 TD [(Yonsei)-452.9(Med)-452.4(J)]TJ /F11 1 Tf -24.6428 -1.2699 TD [(\(2007\))-300.7(48:218)]TJ /F13 1 Tf 5.5182 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(24.)-298(doi:)-301.1(10.3349/ymj.2007.48.2.218)]TJ -7.7103 -1.2699 TD [(51.)-502.1(De)-306.4(Vries)-302.8(MK,)-309.7(Eijk)-298.5(IC,)-304.8(Horst-Bruinsma)-308.4(IE,)-308.1(Peters)-304.8(MJL,)-304.2(Nurmohamed)-313.1(MT,)]TJ 1.6781 -1.2624 TD [(Dijkmans)-351.1(BAC.)-350.5(Erythrocyte)-346.2(Sedimentation)-355.4(Rate,)-348.8(C-reactive)-350.6(Protein)-350.8(Level,)]TJ 0 -1.2699 TD [(and)-248.1(Serum)-239.5(Amyloid)-247.2(a)-243.3(Protein)-244.9(for)-243.4(Patient)-249(Selection)-240.8(and)-248.2(Monitoring)-241.9(of)-244.6(Anti-)]TJ 0 -1.2624 TD [(Tu)-15(mo)-10.8(r)-505.3(N)-9.4(ec)-14.6(ros)-11.7(is)-517.4(F)-9.1(a)0(c)-8.7(t)-7.9(or)-511.8(Tr)-12.2(ea)-8.7(t)-7.9(m)0(e)-11.7(n)0(t)-517.6(i)0(n)-514.3(A)-8.4(nky)-16.3(los)-12.3(in)-15.4(g)-509.6(S)0(p)-9.8(o)0(n)-9.7(d)-9.1(yl)-10.1(it)-12.5(is)-11(.)]TJ /F16 1 Tf 26.8123 0 TD [(A)-9.2(rth)-10.8(ri)-16.1(ti)-10(s)]TJ -26.8123 -1.2699 TD (Rheumatol)Tj /F11 1 Tf 4.6111 0 TD [(\(2009\))-308.2(61\(11\):1484)]TJ /F13 1 Tf 7.6499 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(90.)-298(doi:)-308.6(10.1002/art.24838)]TJ -14.4455 -1.2624 TD [(52.)-502.1(Li)-373.1(T,)-377.5(Huang)-375.7(Z,)-375.8(Zheng)-378.8(B,)-378.2(Liao)-373.4(Z,)-375.8(Zhao)-373(L,)-377.3(Gu)-374.5(J.)-374.7(Serum)-375.6(disease-associated)]TJ 1.6781 -1.2699 TD 0.0159 Tc [(pr)-5.6(ot)-7.1(ei)-3.8(ns)-519.6(of)-517.1(ankyl)-6.2(o)1.9(s)-5.6(i)3.8(ng)-523.9(spo)-5.7(n)-2.5(dyli)-3.8(ti)-3.8(s:)-522(r)-5.6(e)1(s)-5.6(u)-0.8(lts)-519.6(o)-5.7(f)-517(a)-522.2(pre)-6.5(l)1.3(i)-3.8(m)-3.6(inar)-5.6(y)-516.3(s)-5.6(tudy)-523.9(by)]TJ T* 0 Tc [(comparative)-308.9(proteomics.)]TJ /F16 1 Tf 10.2048 0 TD [(Clin)-300.4(Exp)-300.1(Rheumatol)]TJ /F11 1 Tf 8.3831 0 TD [(\(2010\))-300.7(28\(2\):201)]TJ /F13 1 Tf 6.6823 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (7.)Tj -27.4548 -1.2624 TD [(53.)-502.1(Rademacher)-267.9(J,)-261.3(Tietz)-259.7(LM,)-255.8(Le)-262.5(L,)-263.9(Hartl)-260.5(A,)-259.1(Hermann)-263.8(KA,)-258.3(Sieper)-262.2(J,)-261.3(et)-257.1(al.)-259.1(Added)]TJ 1.6781 -1.2699 TD [(value)-254.7(of)-252.2(biomarkers)-256.2(compared)-255.6(with)-248.3(clinical)-254.1(parameters)-254.6(for)-258.6(the)-247.7(prediction)-255(of)]TJ 0 -1.2624 TD 0.0156 Tc [(r)-5.9(a)-0.9(diogr)-5.9(a)-0.9(phi)-4.1(c)-513.3(spi)-4.1(n)-2.8(al)-513(pr)-5.9(ogres)-5.9(s)1.6(i)-4.1(o)1.6(n)-516.8(i)3.5(n)-516.8(a)-1(x)-7.7(i)3.5(al)-520.6(spondyloar)-5.9(thr)-5.9(i)3.5(ti)-4.1(s.)]TJ /F16 1 Tf 25.7843 0 TD 0.0174 Tc [(Rhe)4.2(u)-3.4(m)4.7(a)-0.1(tol)]TJ -25.7843 -1.2699 TD 0 Tc (\(Oxford\))Tj /F11 1 Tf 3.7267 0 TD [(\(2019\))-300.7(58\(9\):1556)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(64.)-298(doi:)-301.1(10.1093/rheumatology/kez025)]TJ -13.0849 -1.2624 TD [(54.)-502.1(Wu)-341.3(J,)-336.9(Wu)-333.7(X,)-338.9(Chen)-335.4(Z,)-338(Lv)-333.8(Q,)-335.6(Yang)-335.2(M,)-340.8(Zheng)-333.5(X,)-338.9(et)-340.3(al.)-334.7(Circulating)-336(Retinol-)]TJ 1.6781 -1.2699 TD [(Binding)-510.7(Protein)-509.5(4)-503.7(a)0(s)-499.2(a)-500.3(Pos)-10.2(sible)-500.4(Biomarker)-514.5(of)-501.6(Treatm)-10.6(ent)-502.3(Response)-513.2(for)]TJ T* 0.0308 Tc [(Ankylos)-5.8(i)3.6(ng)-531.7(Spo)-5.9(n)4.9(d)-8.6(y)5(l)-6.4(i)3.5(ti)-4(s:)-537.3(An)-531.8(Arr)-5.8(a)-0.9(y-B)-6(a)-0.9(sed)-537.7(C)-1.1(om)-3.8(parati)-4(ve)-528.3(St)-7.4(udy.)]TJ /F16 1 Tf 27.9159 0 TD 0.0319 Tc (Front)Tj -27.9159 -1.2624 TD 0 Tc (Pharmacol)Tj /F11 1 Tf 4.5733 0 TD [(\(2020\))-300.7(11:231.)-306(doi:)-301.1(10.3389/fphar.2020.00231)]TJ -6.2514 -1.2699 TD [(55.)-502.1(Liu)-306.6(S,)-304.2(Ji)-302.4(W,)-303.1(Lu)-302.1(J,)-306.6(Tang)-308.4(X,)-301.1(Guo)-305.4(Y,)-298.4(Ji)-310(M,)-303(et)-302.5(al.)-304.5(Discovery)-305.9(of)-305.1(Potential)-300.2(Serum)]TJ 1.6781 -1.2624 TD [(Protein)-411.2(Biomarkers)-415.1(in)-408.5(Ankylosing)-410.8(Spondylitis)-417.5(Using)-407.1(Tandem)-416.9(Mass)-406.7(Tag-)]TJ 0 -1.2699 TD 0.0201 Tc [(Based)-518.2(Q)-4.4(uan)-5.8(t)4.6(itative)-516.4(P)0(roteomics.)]TJ /F16 1 Tf 14.128 0 TD 0.5346 Tc [(JP)512.1(r)513.1(o)518.8(t)511.6(e)513.8(o)511.3(m)521.9(e)-7.7(R)515.3(e)513.8(s)]TJ /F11 1 Tf 7.1585 0 TD 0.0201 Tc [(\(2020\))-513.8(19\(2\):864)]TJ /F13 1 Tf 7.1963 0 TD 0 Tc ()Tj /F11 1 Tf 0.5291 0 TD 0.0199 Tc (72.)Tj -29.012 -1.2624 TD 0 Tc [(doi:)-301.1(10.1021/acs.jproteome.9b00676)]TJ -1.6781 -1.2699 TD [(56.)-502.1(Ma)-348.6(J,)-344.4(Luo)-346.3(X,)-346.5(Wu)-341.3(Q,)-350.7(Chen)-342.9(Z,)-345.5(Kou)-347.4(L,)-347.1(Wang)-347.5(H.)-344.8(Circulation)-346.9(levels)-348.1(of)-342.9(acute)]TJ 1.6781 -1.2699 TD [(phase)-407.9(proteins)-399.2(in)-400.9(patients)-403.2(with)-407(Takayasu)-401.5(arteritis.)]TJ /F16 1 Tf 21.1203 0 TD [(J)-398.6(Vasc)-397.2(Surg)]TJ /F11 1 Tf 5.1478 0 TD [(\(2010\))-399(51)]TJ -26.268 -1.2624 TD (\(3\):700)Tj /F13 1 Tf 2.8271 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(6.)-300.8(doi:)-301.1(10.1016/j.jvs.2009.09.038)]TJ -5.0117 -1.2699 TD [(57.)-502.1(Nair)-354.3(AM,)-349.2(Goel)-348.4(R,)-347.2(Hindhumati)-355.9(M,)-348.3(Jayakanthan)-351.8(K,)-348.1(Visalakshi)-355.7(J,)-352(Joseph)-347.9(G,)]TJ 1.6781 -1.2624 TD [(et)-204.2(al.)-198.6(Serum)-209.3(amyloid)-202.4(A)-197.4(a)0(s)-204.4(a)-205.5(marker)-202.1(of)-199.2(disease)-208.8(activity)-198.7(and)-202.8(treatment)-205(response)]TJ 0 -1.2699 TD [(in)-431.1(Takayasu)-431.7(arteritis.)]TJ /F16 1 Tf 7.4999 0 0 7.4999 391.7479 417.4298 Tm [(Rheumatol)-431.5(Int)]TJ /F11 1 Tf 6.3346 0 TD [(\(2017\))-429.2(37\(10\):1643)]TJ /F13 1 Tf 7.7708 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(9.)-429.3(doi:)-429.6(10.1007/)]TJ -23.7584 -1.2624 TD (s00296-017-3786-2)Tj -1.6781 -1.2699 TD [(58.)-502.1(Hocevar)-315.1(A,)-319.6(Rotar)-315.3(Z,)-315.3(Jese)-318.9(R,)-309.4(Semrl)-320.6(SS,)-312.5(Pizem)-315.7(J,)-314.2(Hawlina)-319.3(M,)-318.1(et)-310(al.)-319.6(Do)-313.1(Early)]TJ 1.6781 -1.2699 TD [(Diagnosis)-373(and)-369.1(Glucocorticoid)-372.3(Treatment)-369.2(Decrease)-372.7(the)-368.6(Risk)-366.9(of)-365.6(Permanent)]TJ 0 -1.2624 TD [(V)-13.6(i)0(s)-11(u)-9.1(a)-9(l)-521(Lo)-12.2(ss)-526.8(a)-9(n)0(d)-526.4(E)0(a)-13.9(r)0(l)-13.4(y)-517.1(R)-13.4(e)0(l)-14.3(a)-9(p)-9.1(s)0(e)-13.7(s)-520.4(in)-521.8(G)-10.1(i)0(a)-13.6(n)-10.8(t)-514.4(C)-9.2(el)-14.3(l)-521(A)-8.4(rt)-14.3(er)-13.7(i)-12.1(t)-7.9(is)-18.5(:)-515.2(A)-514.9(P)-12.5(r)0(o)-12.9(s)0(p)-15.5(e)0(c)-22.2(t)-7.9(iv)-15.2(e)]TJ 0 -1.2699 TD [(Longitudinal)-488.8(Study.)]TJ /F16 1 Tf 8.5872 0 TD [(Med)-490.2(\(Baltimore\))]TJ /F11 1 Tf 7.287 0 TD [(\(2016\))-489.7(95\(14\):e3210.)-488.3(doi:)-490(10.1097/)]TJ -15.8742 -1.2624 TD (MD.0000000000003210)Tj -1.6781 -1.2699 TD [(59.)-502.1(Burja)-378.3(B,)-378.2(Feichtinger)-384(J,)-374.7(Lakota)-380.5(K,)-378.4(Thallinger)-384.2(GG,)-376.7(Sodin-Semrl)-383.7(S,)-372.3(Kuret)-385.2(T,)]TJ 1.6781 -1.2624 TD [(et)-249.6(al.)-244(Utility)-243.4(of)-244.6(serological)-252.4(biomarkers)-248.7(for)-243.4(giant)-247.1(cell)-240.3(arteritis)-249.4(in)-249.7(a)-243.3(large)-244.5(cohort)]TJ 0 -1.2699 TD 0.04 Tc [(o)-4.3(f)-545.9(tr)-4.2(e)-5.1(a)0.8(t)-5.7(m)-2.2(en)-8.6(t-)-6.6(nav)-8.5(e)-541.8(p)0.6(a)-6.8(t)1.8(ie)-5.1(nt)-5.7(s)-4.2(.)]TJ /F16 1 Tf 13.2436 0 TD 0.0403 Tc [(Cli)-7.2(n)-539.9(R)-9.2(h)-1.5(euma)-7.4(to)-5.7(l)]TJ /F11 1 Tf 7.6121 0 TD 0.0428 Tc [(\(2019\))-536.4(38\(2\):317)]TJ /F13 1 Tf 7.5592 0 TD 0 Tc ()Tj /F11 1 Tf 0.5518 0 TD 0.0426 Tc (29.)Tj -28.9667 -1.2699 TD 0 Tc [(doi:)-301.1(10.1007/s10067-018-4240-x)]TJ -1.6781 -1.2624 TD [(60.)-502.1(Dartevel)-377.3(A,)-372.5(Toussaint)-376.4(B,)-378.2(Trocme)-377.9(C,)-373.2(Arnaud)-377.9(M,)-371(Simon)-374.6(N,)-373.4(Faure)-381.1(P,)-376.5(et)-370.5(al.)]TJ 1.6781 -1.2699 TD [(Serum)-458.8(amyloid)-459.4(A)-454.4(a)0(s)-453.8(a)-455(marker)-451.5(of)-456.2(disease)-458.3(activity)-455.7(in)-453.8(Giant)-458.2(cell)-451.9(arteritis.)]TJ /F16 1 Tf 0 -1.2624 TD [(Autoimmun)-304.3(Rev)]TJ /F11 1 Tf 6.8788 0 TD [(\(2020\))-308.2(19\(1\):102428.)-304.3(doi:)-301.1(10.1016/j.autrev.2019.102428)]TJ -8.557 -1.2699 TD [(61.)-502.1(Van)-366(Sleen)-365.7(Y,)-358.9(Sandovici)-365.5(M,)-363.5(Abdulahad)-360.2(WH,)-367.1(Bijzet)-358.2(J,)-367.1(van)-363.1(der)-363(Geest)-364.1(SMK,)]TJ 1.6781 -1.2624 TD [(Boots)-358.9(AMH,)-367.8(et)-363(al.)-357.4(Markers)-362.3(of)-365.5(angiogenesis)-367.1(and)-361.5(macrophage)-362.6(products)-364.2(for)]TJ 0 -1.2699 TD [(predicting)-221.4(disease)-216.4(course)-224.4(and)-217.9(monitoring)-216.7(vascular)-216.1(in)]TJ /F12 1 Tf 20.8103 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(ammation)-215.2(in)-219.5(giant)-216.8(cell)]TJ -21.347 -1.2699 TD (arteritis.)Tj /F16 1 Tf 3.6813 0 TD (Rheumatology)Tj /F11 1 Tf 6.0322 0 TD [(\(2019\))-391.4(58\(8\):1383)]TJ /F13 1 Tf 7.2568 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(92.)-396.3(doi:)-391.8(10.1093/rheumatology/)]TJ -17.4768 -1.2624 TD (kez034)Tj -1.6781 -1.2699 TD [(62.)-502.1(Mitani)-278.2(Y,)-275.7(Sawada)-282(H,)-276.8(Hayakawa)-274.9(H,)-276.8(Aoki)-278.8(K,)-280.1(Ohashi)-275(H,)-276.8(Matsumura)-280(M,)-280.3(et)-272.2(al.)]TJ 1.6781 -1.2624 TD [(Elevated)-320.3(levels)-325.4(of)-312.6(high-sensitivity)-328.9(C-reactive)-320.4(protein)-317.2(and)-323.7(serum)-320.9(amyloid-A)]TJ 0 -1.2699 TD [(la)-8.4(te)-514.1(afte)-12.9(r)-505.3(Kaw)-11.5(a)-9(sak)-10.2(i)-503.5(d)-9.1(ise)-10.7(ase)-15.1(:)-507.7(asso)-13.1(cia)-13.3(tio)-11.4(n)-502.2(b)0(e)-13.8(twe)-11(en)-509.5(in)]TJ /F12 1 Tf 21.6267 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(amm)-10.2(at)-9.4(ion)-513.2(and)-512.7(la)-8.4(t)-7.9(e)]TJ -22.1634 -1.2624 TD [(coronary)-464.1(sequelae)-458.1(in)-453.8(Kawasaki)-466.1(disease.)]TJ /F16 1 Tf 16.7738 0 TD (Circulation)Tj /F11 1 Tf 4.9286 0 TD [(\(2005\))-451.9(111\(1\):38)]TJ /F13 1 Tf 6.841 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (43.)Tj -29.0498 -1.2699 TD [(doi:)-301.1(10.1161/01.CIR.0000151311.38708.29)]TJ -1.6781 -1.2699 TD [(63.)-502.1(Whitin)-373.3(JC,)-368.7(Yu)-366.8(TT,)-368.2(Ling)-364.3(XB,)-368.2(Kanegaye)-373.8(JT,)-372.9(Burns)-364.4(JC,)-368.7(Cohen)-372.1(HJ.)-370.6(A)-363.7(Novel)]TJ 1.6781 -1.2624 TD [(Truncated)-246.7(Form)-238(of)-237(Serum)-239.5(Amyloid)-239.6(A)-242.8(i)0(n)-234.6(Kawasaki)-239.3(Disease.)]TJ /F16 1 Tf 23.8038 0 TD [(PloS)-240.8(One)]TJ /F11 1 Tf 3.8249 0 TD (\(2016\))Tj -27.6287 -1.2699 TD [(11\(6\):e0157024.)-308.9(doi:)-301.1(10.1371/journal.pone.0157024)]TJ -1.6781 -1.2624 TD [(64.)-502.1(Purevdorj)-233.7(N,)-229.8(Mu)-235.3(Y,)-222.8(Gu)-230.9(Y,)-230.4(Zheng)-235.2(F,)-229.6(Wang)-234.1(R,)-226.3(Yu)-230.8(J,)-231(et)-226.9(al.)-236.4(Clinical)-225.7(signi)]TJ /F12 1 Tf 29.1481 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (cance)Tj -27.9991 -1.2699 TD [(of)-259.7(the)-262.8(serum)-267.9(biomarker)-264.9(index)-266.8(detection)-265.3(in)-257.3(children)-269.9(with)-263.4(Henoch-Schonlein)]TJ 0 -1.2624 TD 0.0236 Tc [(pu)6.9(rpu)6.9(r)2.1(a)7(.)]TJ /F16 1 Tf 4.15 0 TD 0.0189 Tc [(Cli)-5.9(n)-515.9(B)-6.3(i)1.7(o)-4.4(c)0.8(hem)]TJ /F11 1 Tf 6.2968 0 TD 0.0196 Tc [(\(2018\))-521.8(52:167)]TJ /F13 1 Tf 5.9717 0 TD 0 Tc ()Tj /F11 1 Tf 0.5291 0 TD 0.0201 Tc [(70.)-525.4(doi:)-517.8(10.1016/j.clinbio)6.1(c)-2.3(hem.)]TJ -16.9476 -1.2699 TD 0 Tc (2017.11.006)Tj -1.6781 -1.2699 TD [(65.)-502.1(Kuret)-249.2(T,)-249(Lakota)-244.5(K,)-242.3(Z)]TJ /F20 1 Tf 9.8345 0.2646 TD ()Tj /F11 1 Tf 0.1058 -0.2646 TD [(igon)-244.2(P,)-248(Ogric)]TJ /F20 1 Tf 5.2612 0.0454 TD ()Tj /F11 1 Tf 0.257 -0.0454 TD [(M,)-242.5(Sodin-S)]TJ /F20 1 Tf 4.4145 0.257 TD ()Tj /F11 1 Tf 0.0454 -0.257 TD [(emrl)-244.3(S,)-251.3(C)]TJ /F20 1 Tf 3.5377 0.257 TD ()Tj /F11 1 Tf 0.1361 -0.257 TD (uc)Tj /F20 1 Tf 0.9298 0.0454 TD ()Tj /F11 1 Tf 0.0076 -0.0454 TD [(nik)-252.1(S,)-243.8(et)-242(al.)-251.5(Insight)]TJ -22.8513 -1.2624 TD [(into)-415.3(in)]TJ /F12 1 Tf 2.8271 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-421(cell)-414.2(and)-422(cytokine)-420.2(pro)]TJ /F12 1 Tf 13.3948 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(les)-421.3(in)-416(adult)-420.1(IgA)-419.3(vasculitis.)]TJ /F16 1 Tf 11.2783 0 TD (Clin)Tj -28.5585 -1.2699 TD (Rheumatol)Tj /F11 1 Tf 4.6111 0 TD 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[(\()18(2)0(0)20.7(1)17.9(5\))-213.6(10)20.7(\()18(1)0(\))20.7(:)0(e)29.3(0)0(1)28.2(1)0(0)20.7(8)17.9(20)20.7(.)-220.4(d)0(o)22.2(i)0(:)-217.4(1)17.9(0.)24.2(13)28.2(71)28.2(/j)20.2(o)16.2(u)0(r)22.3(n)0(a)25.6(l)15.7(.p)27.4(on)20.5(e)15.4(.)0(0)24.2(1)17.9(10)20.7(8)17.9(2)0(0)]TJ -3.5074 -1.2699 TD [(75.)-502.1(Lis-S)]TJ /F20 1 Tf 3.5982 0.2495 TD ()Tj /F11 1 Tf 0.0605 -0.2495 TD (wi)Tj /F23 1 Tf 0.9373 0 TD ()Tj /F11 1 Tf 0.4158 0 TD [(ty)-222.7(A,)-228.9(Widuchowska)-229.2(M,)-227.4(Brzezin)]TJ /F20 1 Tf 12.2534 0.0454 TD ()Tj /F11 1 Tf 0.1058 -0.0454 TD (ska-Wcis)Tj /F23 1 Tf 3.6511 0 TD ()Tj /F11 1 Tf 0.2721 0 TD [(o)-225.7(L)0(,)-226.1(Kucharz)-225.4(E.)-225.4(High)-228.5(acute)]TJ -19.616 -1.2624 TD [(phase)-483.5(protein)-483.5(levels)-484.1(correlate)-488.4(with)-482.6(pulmonary)-481.2(and)-490(skin)-477.7(involvement)-488.5(in)]TJ 0 -1.2699 TD [(patients)-433.4(with)-437.3(dif)65.6(fuse)-434.8(systemic)-440.5(sclerosis.)]TJ /F16 1 Tf 16.5923 0 TD [(J)-436.4(Int)-429(Med)-429.7(Res)]TJ /F11 1 Tf 6.2968 0 TD [(\(2018\))-436.8(46:1634)]TJ /F13 1 Tf 6.1305 0 TD ()Tj /F11 1 Tf 0.514 0 TD (9.)Tj -29.5336 -1.2624 TD [(doi:)-301.1(10.1177/0300060518760955)]TJ -1.6781 -1.2699 TD [(76.)-502.1(Wang)-271.9(CM,)-266.8(Deng)-267.3(JH,)-264.7(Mao)-271.9(GF,)-269.9(He)-267.8(JL,)-267(Shi)-267.9(X.)-263.3(Serum)-269.8(Amyloid)-269.9(A:)-266.7(A)-265.5(Potential)]TJ 1.6781 -1.2699 TD [(Biomarker)-454.1(Assessing)-445.3(Disease)-453.4(Activity)-447.6(in)-446.3(Systemic)-449.8(Lupus)-455.2(Erythematosus.)]TJ /F16 1 Tf 0 -1.2624 TD [(Med)-301.2(Sci)-303(Monit)]TJ /F11 1 Tf 6.2212 0 TD [(\(2020\))-308.2(26:e923290.)-297.4(doi:)-308.6(10.12659/MSM.923290)]TJ -7.8993 -1.2699 TD [(77.)-502.1(Boyd)-403.3(TA,)-401(Eastman)-400.1(PS,)-399.9(Huynh)-402.6(DH,)-394.4(Qureshi)-404.1(F,)-395.9(Sasso)-406.9(EH,)-395.1(Bolce)-397.5(R,)-400.1(et)-400.7(al.)]TJ 1.6781 -1.2624 TD [(Correlation)-368.8(of)-365.5(serum)-366.2(protein)-362.5(biomarkers)-369.6(with)-361.7(disease)-367.6(activity)-372.5(in)-363.1(psoriatic)]TJ 0 -1.2699 TD [(a)-9(r)0(t)-14.3(h)-13.3(ri)-11(t)-7.9(i)-12.1(s.)]TJ /F16 1 Tf 3.9912 0 TD [(Ex)-15.6(pe)-18(rt)-520.8(Re)-17.4(v)-515.5(C)-10(li)-12.6(n)-512.2(I)0(m)-19.9(m)0(u)-10.8(n)-13.3(ol)]TJ /F11 1 Tf 11.505 0 TD [(\(2)-9.5(0)-12.3(2)0(0)-17.1(\))-511.2(16)-17.1(\(3)-17.1(\):)-13.5(33)-17.1(5)]TJ /F13 1 Tf 6.9998 0 TD ()Tj /F11 1 Tf 0.5216 0 TD [(41)-17.1(.)-515.2(d)0(o)-15.6(i)0(:)-519.8(1)0(0)-17.1(.)-8.8(10)-17.1(80)-9.6(/)]TJ -23.0176 -1.2624 TD (1744666X.2020.1729129)Tj -1.6781 -1.2699 TD [(78.)-502.1(Du)24.4(z)15.4(o)0(v)20.7(a)-228.2(A,)-213.7(B)16.1(a)0(k)26.5(k)0(a)26.5(l)0(o)24.3(g)0(l)27.7(u)-228.4(A,)-213.7(B)16.1(e)0(s)24.1(b)0(a)22.4(s)-225.6(N,)-214.7(T)16.8(o)0(p)22.2(a)0(l)29.4(o)0(g)20.7(l)15.7(u)-228.4(R)16.8(,)-228(O)0(z)21.1(e)15.4(n)-230(S)14.5(,)-228(O)0(z)28.7(a)0(l)21.8(t)0(i)25.3(n)-222.5(F,)-214.4(et)-211.8(al)21.8(.)-228(R)16.8(ol)24.3(e)]TJ 1.6781 -1.2699 TD [(of)-237(A-)28.1(S)14.5(A)0(A)-236.1(i)18.1(n)-245.2(m)0(o)27(n)0(i)22.4(t)0(o)23.4(r)16.3(in)22.4(g)-245(s)16.3(ub)22.2(c)15.4(l)15.7(in)22.4(i)18.1(c)0(a)21.5(l)-241.3(in)]TJ /F12 1 Tf 14.9066 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(am)24.4(ma)24.4(ti)25.3(o)16.2(n)-245.2(an)25.6(d)-251(i)18.1(n)-245.2(c)0(o)24(l)15.7(ch)24.8(ic)25.9(in)22.4(e)-241.6(d)0(o)22.2(s)16.3(ag)25.7(e)-249.2(i)18.1(n)]TJ -15.4207 -1.2624 TD [(fa)25(mi)21.3(l)15.7(i)0(a)24.2(l)-286.7(M)15.7(e)15.4(di)24.1(te)22.6(r)16.3(r)0(a)22.4(n)0(e)27.2(a)0(n)-276.8(f)0(e)26.7(v)0(e)27.4(r)0(.)]TJ /F16 1 Tf 11.6109 0 TD [(Cl)24.9(in)-280(E)15.3(x)14.5(p)-284.5(R)0(h)22(e)0(u)26.5(m)0(a)22.8(t)0(o)29.2(l)]TJ /F11 1 Tf 7.4999 0 0 7.4999 210.7842 312.9448 Tm [(\()18(2)0(0)20.7(0)17.9(3\))-274.1(21)20.7(:5)31.8(09)]TJ /F13 1 Tf 5.3594 0 TD ()Tj /F11 1 Tf 0.4913 0 TD [(14)20.7(.)]TJ -27.3112 -1.2699 TD [(79.)-502.1(Lachmann)-259.2(HJ,)-257.2(Sengl)-264.8(B,)-249.7(Yavuzs)]TJ /F20 1 Tf 14.5362 0 TD ()Tj /F11 1 Tf T* [(en)-252.5(TU,)-260.7(Booth)-252.4(DR,)-260.7(Booth)-252.4(SE,)-263.8(Bybee)-257.6(A,)-251.5(et)-257.1(al.)]TJ -12.8581 -1.2624 TD 0.0634 Tc [(Cli)5.9(n)-0.3(ical)-563.5(and)-558(s)4.1(ub)4(cl)3.5(inical)-563.5(i)5.9(n)]TJ /F12 1 Tf 12.7674 0 TD 0 Tc ()Tj /F11 1 Tf 0.5972 0 TD 0.0621 Tc [(ammation)-561(in)-561(pat)-6.3(i)4.6(ents)-564.2(with)-563.4(familial)]TJ -13.3646 -1.2699 TD 0 Tc [(Medi)-12.9(terrane)-17.3(an)-503.6(fever)-511.7(and)-512.7(in)-499.2(hete)-13.1(rozyg)-11.2(ous)-505.8(carri)-11(ers)-511.4(of)-501.6(MEFV)-510.8(mutat)-15.7(ions.)]TJ /F16 1 Tf 0 -1.2624 TD [(Rheumatol)-212.3(\(Oxford\))]TJ /F11 1 Tf 8.1488 0 TD [(\(2006\))-210(45\(6\):746)]TJ /F13 1 Tf 6.5916 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(50.)-207.3(doi:)-202.8(10.1093/rheumatology/kei279)]TJ -16.9249 -1.2699 TD [(80.)-502.1(Berkun)-345(Y,)-343.8(Padeh)-346(S,)-349.6(Reichman)-342.1(B,)-348(Zaks)-346.9(N,)-343.2(Rabinovich)-343.5(E,)-346.3(Lidar)-344.7(M,)-340.8(et)-347.8(al.)-342.3(A)]TJ 1.6781 -1.2699 TD [(Single)-441.7(Testing)-431.5(of)-433.6(Serum)-443.6(Amyloid)-436.2(A)-431.8(Levels)-437.5(as)-431.1(a)-439.9(Tool)-434(for)-432.4(Diagnosis)-441(and)]TJ 0 -1.2624 TD [(Tr)-12.2(ea)-8.7(t)-7.9(men)-14.9(t)-506.8(D)0(i)-8.8(lem)-11.1(ma)-13.4(s)-505.3(i)0(n)-514.3(F)-9.1(ami)-10.4(li)-11.6(a)-9(l)-505.9(Med)-15.9(ite)-12.2(rr)-12.8(ane)-12(a)-9(n)-509.7(Fev)-12(er.)]TJ /F16 1 Tf 23.8567 0 TD [(Se)-8.7(min)-519.4(Art)-16(hri)-12.5(ti)-10(s)]TJ -23.8567 -1.2699 TD (Rheumatol)Tj /F11 1 Tf 4.6111 0 TD [(\(2007\))-308.2(37:182)]TJ /F13 1 Tf 5.5257 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(8.)-300.8(doi:)-301.1(10.1016/j.semarthrit.2007.03.005)]TJ -12.3214 -1.2624 TD [(81.)-502.1(Yalc)]TJ /F20 1 Tf 3.3865 0 TD ()Tj /F11 1 Tf 0.0227 0 TD [(inkaya)-242.9(F,)-237.1(Cakar)-240(N,)-237.3(Acar)-235.2(B,)-242.2(Tutar)-234.8(E,)-240.5(Griz)-241.6(H,)-231.5(Elhan)-241.5(AH,)-239.9(et)-234.4(al.)-236.4(The)-238.1(value)]TJ -1.731 -1.2699 TD 0.0233 Tc [(of)-524.8(the)-528.3(l)1.2(evels)-519.8(o)1.7(f)-524.8(a)-0.8(cute)-520.7(ph)-5.1(a)6.7(s)-5.8(e)-520.7(r)1.8(eactants)-519.8(for)-519.8(t)0.3(h)-5.1(e)-520.7(prediction)-524.2(of)-464.3(fa)6.8(milial)]TJ 0 -1.2624 TD 0.0382 Tc [(M)-6.6(e)0.7(di)-4.2(te)-6.9(rr)-6(anea)-8.6(n)-539.6(f)-3.4(eve)-6.9(r)-542.7(as)-6(so)-6.1(ci)-4.2(ate)-6.9(d)-537.9(a)-8.6(m)3.6(yl)-6.6(oi)-4.2(do)-6.1(si)-4.2(s:)-545.1(a)-545.3(c)0.7(as)-6(e)-543.6(c)0.7(o)-6.1(n)-2.9(tr)-6(ol)-543.3(st)-7.5(udy.)]TJ /F16 1 Tf 0 -1.2699 TD 0 Tc [(Rheumatol)-303(Int)]TJ /F11 1 Tf 6.0776 0 TD [(\(2007\))-308.2(27\(6\):517)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(22.)-305.6(doi:)-301.1(10.1007/s00296-006-0265-6)]TJ -14.952 -1.2699 TD [(82.)-502.1(Kallinich)-350(T,)-339.7(Wittkowski)-347.7(H,)-337.3(Keitzer)-349.9(R,)-339.7(Roth)-343.4(J,)-344.4(Foell)-339.3(D.)-345.6(Neutrophil-derived)]TJ 1.6781 -1.2624 TD [(S100A12)-456.3(as)-453.8(novel)-458(biomarker)-453.9(of)-456.3(in)]TJ /F12 1 Tf 14.5287 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammation)-457.1(in)-453.8(familial)-457.5(Mediterranean)]TJ -15.0578 -1.2699 TD (fever.)Tj /F16 1 Tf 2.4718 0 TD [(Ann)-300.3(Rheum)-296.8(Dis)]TJ /F11 1 Tf 6.7276 0 TD [(\(2010\))-300.7(69\(4\):677)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(82.)-305.6(doi:)-301.1(10.1136/ard.2009.114363)]TJ -18.0739 -1.2624 TD [(83.)-502.1(Lofty)-359.6(HM,)-359.4(Marzouk)-365.1(H,)-360(Farag)-361.6(Y,)-358.9(Nabih)-360.1(M,)-363.5(Khalifa)-363.3(IAS,)-357.6(Mostafa)-359.4(N,)-365.8(et)-355.4(al.)]TJ 1.6781 -1.2699 TD [(Serum)-292.5(Amyloid)-292.5(A)-288.1(Level)-295(in)-287.5(Egyptian)-294.4(Children)-294.4(with)-286.1(Familial)-296.5(Mediterranean)]TJ 0 -1.2624 TD (Fever.)Tj /F16 1 Tf 2.6986 0 TD [(Int)-300.5(J)-300.3(Rheumatol)]TJ /F11 1 Tf 6.6898 0 TD [(\(2016\))-300.7(1:1)]TJ /F13 1 Tf 4.0819 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(6.)-300.8(doi:)-301.1(10.1155/2016/7354018)]TJ -15.6626 -1.2699 TD [(84.)-502.1(Cakan)-403.2(M,)-401.3(Karadag)-400.1(SG,)-397.5(Tanatar)-405.6(A,)-395.2(Sonmez)-407.3(HE,)-395.1(Ayaz)-405.8(NA.)-397(The)-396.8(Value)-401.3(of)]TJ 1.6781 -1.2699 TD [(Serum)-239.5(Amyloid)-239.6(A)-235.2(Levels)-233.4(in)-234.6(Familial)-236.1(Mediterranean)-246.5(Fever)-237.3(to)-233.6(Identify)-235.2(Occult)]TJ 0 -1.2624 TD (In)Tj /F12 1 Tf 0.8769 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammation)-366.4(During)-370.8(Asymptomatic)-366.2(Periods.)]TJ /F16 1 Tf 17.5146 0 TD [(J)-368.3(Clin)-360.8(Rheumatol)]TJ /F11 1 Tf 7.3853 0 TD [(\(2021\))-361.2(27)]TJ -26.3058 -1.2699 TD (\(1\):1)Tj /F13 1 Tf 1.8671 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(4.)-300.8(doi:)-308.6(10.1097/RHU.0000000000001134)]TJ -4.0517 -1.2624 TD [(85.)-502.1(Bilginer)-345.2(Y,)-343.8(Ozaltin)-335.6(F,)-343(Basaran)-344.4(C,)-343(Duzova)-341.6(A,)-342.3(Besbas)-337(N,)-343.2(Topaloglu)-342.8(R,)-339.7(et)-340.3(al.)]TJ 1.6781 -1.2699 TD [(Evaluation)-344(of)-335.3(intima)-343.6(media)-336.7(thickness)-346(of)-335.3(the)-338.4(common)-342.2(and)-338.9(internal)-335.9(carotid)]TJ 0 -1.2624 TD [(a)-9(rte)-14.1(ri)-11(es)-520.2(wit)-15.8(h)-512.2(i)0(n)]TJ /F12 1 Tf 6.5916 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(amm)-17.7(at)-9.3(or)-12.9(y)-509.6(m)0(a)-13.4(r)0(k)-8.7(e)0(r)-13.7(s)-512.9(in)-514.3(fa)-12.8(mi)-8.9(li)-11.6(a)-9(l)-505.9(Me)-14.3(d)-9.1(i)0(t)-12.5(err)-12.5(a)-9(n)0(e)-10.6(a)-9(n)-509.7(f)0(e)-11.1(v)0(e)-10.4(r)-512.9(a)-9(s)]TJ 27.6438 84.8666 TD [(possible)-356.1(predictors)-358.3(for)-349.3(atherosclerosis.)]TJ /F16 1 Tf 15.844 0 TD [(Rheumatol)-355.9(Int)]TJ /F11 1 Tf 6.1834 0 TD [(\(2008\))-346(28\(12\):1211)]TJ /F13 1 Tf 7.6877 0 TD ()Tj /F11 1 Tf -29.715 -1.2699 TD [(6.)-300.8(doi:)-301.1(10.1007/s00296-008-0605-9)]TJ -1.6781 -1.2624 TD [(86.)-502.1(Mohamed)-253(R,)-256.5(El-Bassyouni)-257.1(HT,)-252.4(Elwan)-246.7(SH,)-254.8(Youness)-253(E,)-255.6(Soliman)-254.5(DR,)-253.2(Shehata)]TJ 1.6781 -1.2699 TD [(GM,)-343.3(et)-340.3(al.)-342.3(Carotid)-339.9(intima-media)-349(thickness,)-347.2(lipid)-344.3(pro)]TJ /F12 1 Tf 21.3848 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(le,)-340.6(serum)-343.5(amyloid)-346(A)]TJ -21.914 -1.2624 TD [(and)-225.5(vitamin)-225.8(D)-215.9(status)-228.2(in)-219.5(children)-224.5(with)-218(familial)-223.2(Mediterranean)-231.4(fever.)]TJ /F16 1 Tf 26.7518 0 TD (Egyptian)Tj -26.7518 -1.2699 TD (Rheumatologist)Tj /F11 1 Tf 6.4026 0 TD [(\(2020\))-308.2(42\(3\):237)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(40.)-305.6(doi:)-301.1(10.1016/j.ejr.2020.05.005)]TJ -15.277 -1.2699 TD [(87.)-502.1(Sargsyan)-403.7(Y,)-404.3(Sargsyan)-403.7(A.)-402.7(Endothelial)-404.9(biomarkers)-407.4(in)-400.9(patients)-410.8(with)-399.5(familial)]TJ 1.6781 -1.2624 TD [(Mediterranean)-367.5(fever)-368.1(associated)-368.3(vascular)-359.7(disease)-367.6(and)-361.5(vasculopathy.)]TJ /F16 1 Tf 27.3566 0 TD (Pediatr)Tj -27.3566 -1.2699 TD (Rheumatol)Tj /F11 1 Tf 4.6111 0 TD [(\(2015\))-308.2(13\(1\):O16.)-302.1(doi:)-301.1(10.1186/1546-0096-13-S1-O16)]TJ -6.2892 -1.2624 TD [(88.)-502.1(Aygndz)-218.9(M,)-212.3(Bavbek)-216.2(N,)-207.1(ztrk)-216.3(M,)-212.3(Kaftan)-213.6(O,)-214.7(Kos)]TJ /F20 1 Tf 21.5511 0 TD ()Tj /F11 1 Tf T* [(ar)-211.9(A.)-213.7(Kirazli)-211.9(A.Serum)-218.9(beta)]TJ -19.873 -1.2699 TD [(2-microglobulin)-346.7(re)]TJ /F12 1 Tf 7.5969 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ects)-346.4(disease)-344.9(activity)-342.3(in)-340.4(Behc)]TJ /F20 1 Tf 11.2707 0 TD ()Tj /F11 1 Tf 0.0227 0 TD (et)Tj /F13 1 Tf 0.7181 0 TD ()Tj /F11 1 Tf 0.2192 0 TD [(s)-346.6(disease.)]TJ /F16 1 Tf 4.0517 0 TD [(Rheumatol)-348.4(Int)]TJ /F11 1 Tf -24.4085 -1.2624 TD [(\(2002\))-300.7(22\(1\):5)]TJ /F13 1 Tf 5.7298 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(8.)-300.8(doi:)-301.1(10.1007/s00296-002-0180-4)]TJ -7.9144 -1.2699 TD [(89.)-502.1(Cantarini)-223.4(L,)-218.6(Pucino)-224.6(V,)-218.9(Vitale)-215.6(A,)-221.3(Talarico)-221.8(R,)-218.7(Lucherini)-220.2(OM,)-221.6(Magnotti)-223(F.)-214.4(et)-219.3(al.)]TJ 1.6781 -1.2699 TD 0.0354 Tc [(Imm)8.3(u)-4(no)6.3(metabo)6.3(lic)-531.3(b)6.3(io)6.3(mar)6.3(k)2.8(er)6.3(s)-537.9(o)6.3(f)-535.3(i)8.2(n)]TJ /F12 1 Tf 16.0783 0 TD 0 Tc ()Tj /F11 1 Tf 0.5669 0 TD 0.0354 Tc [(ammati)8.1(on)-534.8(i)8.2(n)-534.8(B)6.1(e)-2.2(hc)]TJ /F20 1 Tf 8.3302 0 TD 0 Tc ()Tj /F11 1 Tf 0.0529 0 TD 0.0375 Tc (et)Tj /F13 1 Tf 0.7862 0 TD 0 Tc ()Tj /F11 1 Tf 7.4999 0 0 7.4999 518.6833 588.4156 Tm 0.5658 Tc [(sd)526.4(i)531(s)536.7(e)528.2(a)534.1(s)529.2(e)535.8(:)]TJ -26.064 -1.2624 TD 0 Tc [(relationship)-425.4(with)-429.7(epidemiological)-422.3(pro)]TJ /F12 1 Tf 15.4585 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(le,)-423.7(disease)-428(activity)-425.4(and)-422(therapeutic)]TJ -15.9876 -1.2699 TD (regimens.)Tj /F16 1 Tf 4.1273 0 TD [(Clin)-270.1(Exp)-269.8(Immunol)]TJ /F11 1 Tf 7.6347 0 TD [(\(2016\))-278(184\(2\):197)]TJ /F13 1 Tf 7.1358 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(207.)-265(doi:)-270.8(10.1111/cei.12768)]TJ -21.09 -1.2624 TD [(90.)-502.1(Vitale)-382(A,)-387.6(Rigante)-381.1(D,)-383.4(Lupalco)-378.8(G,)-381.7(Brizi)-384.7(MG,)-381.1(Caso)-378.8(F,)-388.3(Franceschini)-384.1(R,)-385(et)-378.1(al.)]TJ 1.6781 -1.2699 TD [(Serum)-292.5(amyloid)-293.1(A)-295.7(i)0(n)-287.5(Behcet)]TJ /F13 1 Tf 11.1422 0 TD ()Tj /F11 1 Tf 0.2192 0 TD [(s)-293.6(disease.)]TJ /F16 1 Tf 3.9459 0 TD [(Clin)-292.8(Rheumatol)]TJ /F11 1 Tf 6.5613 0 TD [(\(2014\))-293.1(33\(8\):1165)]TJ /F13 1 Tf 7.151 0 TD ()Tj /F11 1 Tf 0.514 0 TD (7.)Tj -29.5336 -1.2624 TD [(doi:)-301.1(10.1007/s10067-014-2555-9)]TJ -1.6781 -1.2699 TD [(91.)-502.1(Sota)-356.6(J,)-359.5(Vitale)-359.3(A,)-357.4(Rigante)-358.5(D,)-353.2(Orlando)-360.5(I,)-356.1(Lucherini)-363.8(OM,)-357.7(Simpatico)-356.3(A,)-357.4(et)-355.4(al.)]TJ 1.6781 -1.2699 TD [(Correlation)-210(of)-206.8(Serum)-209.3(Amyloid-A)-211.5(Levels,)-211.9(Clinical)-210.6(Manifestations,)-208.9(Treatment,)]TJ 0 -1.2624 TD [(and)-210.4(Disease)-211.5(Activity)-213.2(in)-204.4(Patients)-210(with)-210.5(Behc)]TJ /F20 1 Tf 16.5697 0 TD ()Tj /F11 1 Tf 0.0227 0 TD (et)Tj /F13 1 Tf 0.7181 0 TD ()Tj /F11 1 Tf 0.2192 0 TD [(s)-202.9(Disease.)]TJ /F16 1 Tf 3.9837 0 TD [(Isr)-209.7(Med)-210.5(Assoc)-208.6(J)]TJ /F11 1 Tf 6.1153 0 TD (\(2018\))Tj -27.6287 -1.2699 TD (20\(8\):517)Tj /F13 1 Tf 3.7796 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(21.)-298(doi:)-301.1(10.1038/s41433-019-0740-4)]TJ -5.9717 -1.2624 TD [(92.)-502.1(Le)24.8(e)-150.9(H)0(J)23.7(,)-152.4(K)15.9(i)0(m)-145(J)0(H)31.3(,)-152.4(Ki)18.9(m)-148(S)14.5(W,)-144.4(Jo)28.3(o)-150.1(H)0(A)25.9(,)-152.4(Le)24.8(e)-150.9(H)0(W)19.6(,)-152.4(K)15.9(i)0(m)-137.5(Y)0(S)27.2(,)-152.4(et)-143.7(al)29.4(.)-152.4(P)0(r)26.5(o)0(t)23.4(e)15.4(om)26.9(ic)-140.4(An)26.1(al)21.8(ys)28.3(is)-139.5(o)16.2(f)]TJ 1.6781 -1.2699 TD [(S)14.5(e)0(r)24.1(u)0(m)-164.7(A)0(m)25(y)0(l)27.7(o)16.2(id)-164.9(A)-174.7(a)0(s)-159(a)-175.3(Po)26.4(te)22.6(nt)26.6(i)18.1(a)0(l)-167.2(M)15.7(ar)22.4(ke)28.1(r)-172.7(i)0(n)-166.6(I)15.5(nt)26.6(e)15.4(s)0(t)23.5(i)0(n)22.4(a)0(l)-159.6(B)16.1(e)15.4(h)0(c)]TJ /F20 1 Tf 22.0803 0 TD ()Tj /F11 1 Tf 0.0076 0 TD (et)Tj /F13 1 Tf 0.6954 0 TD ()Tj /F11 1 Tf 0.2041 0 TD [(s)-172.7(D)0(i)21.4(s)16.3(ea)21.5(s)16.3(e)15.4(.)]TJ /F16 1 Tf 3.8249 0 TD [(Di)22.1(g)15.4(e)0(s)25(t)0(i)20.2(v)0(e)]TJ -26.8123 -1.2624 TD [(Di)22.1(s)-226.4(S)0(c)24.2(i)]TJ /F11 1 Tf 2.8044 0 TD [(\(2)20.7(0)17.9(1)0(7)20.7(\))-223.9(62)28.2(\(8)20.7(\))18(:)0(1)24.2(9)0(5)28.2(3)]TJ /F13 1 Tf 6.8939 0 TD ()Tj /F11 1 Tf 0.4989 0 TD -0.0283 Tc [(6)-10.4(2)-28.3(.)-246(d)-28.3(oi)-28.3(:)-245.7(1)-28.3(0.)-28.3(10)-28.3(07)-28.3(/)-5.9(s)-12(1)-28.3(0)-7.6(6)-10.4(2)-28.3(0)-7.6(-)-28.3(01)-28.3(7)-7.6(-)-28.3(46)-28.3(06)-28.3(-y)]TJ -11.8754 -1.2699 TD 0 Tc [(93)-9.6(.)-507.7(H)0(a)-12.5(wki)-10.2(ns)-516.1(PN,)-514.4(La)-14.7(chm)-9.8(a)-9(n)0(n)-513(HJ,)-521.7(Aga)-13(nna)-514.4(E,)-520.2(McD)-11(er)-13.7(mot)-11.2(t)-506.8(MF.)-523.8(Sp)-9.8(ect)-15(rum)-518.8(of)]TJ 1.6932 -1.2699 TD [(Clinical)-414.7(Features)-417.9(in)-416(Muckle-Wells)-416.3(Syndrome)-418.6(and)-414.5(Response)-422.5(to)-415(Anakinra.)]TJ /F16 1 Tf 0 -1.2624 TD [(Arthritis)-302.7(Rheumatol)]TJ /F11 1 Tf 8.2848 0 TD [(\(2004\))-300.7(50\(2\):607)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(12.)-305.6(doi:)-301.1(10.1002/art.2003)]TJ -17.1744 -1.2699 TD [(94.)-502.1(Scarpioni)-278.1(R,)-264.1(Rigante)-275.3(D,)-270(Cantarini)-268.8(L,)-271.5(Ricardi)-273.6(M,)-265.2(Albertazzi)-275.8(V,)-271.8(Melfa)-268.4(L,)-271.5(et)-264.7(al.)]TJ 1.6781 -1.2624 TD [(Renal)-417.9(involvement)-412.9(in)-416(secondary)-413.6(amyloidosis)-415.2(of)-418.5(Muckle-Wells)-416.3(syndrome:)]TJ 0 -1.2699 TD [(marked)-356(improvement)-359(of)-350.4(renal)-358(function)-355.6(and)-346.4(reduction)-356.3(of)-358(proteinuria)-353.8(after)]TJ 0 -1.2624 TD [(therapy)-237.5(with)-240.7(human)-235.5(anti-interleukin1)]TJ /F17 1 Tf 15.0956 0 TD (b)Tj /F11 1 Tf 0.7786 0 TD [(monoclonal)-234.4(antibody)-238.9(canakinumab.)]TJ /F16 1 Tf -15.8742 -1.2699 TD [(Clin)-300.4(Rheumatol)]TJ /F11 1 Tf 6.584 0 TD [(\(2015\))-300.7(34:1311)]TJ /F13 1 Tf 5.9944 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(6.)-300.8(doi:)-301.1(10.1007/s10067-013-2481-2)]TJ -14.7706 -1.2699 TD [(95.)-502.1(Hof)61.9(fman)-254.8(HM,)-246(Throne)-254.2(ML,)-248.2(Amar)-247.4(NJ,)-255.5(Cartwright)-252.5(RC,)-243(Kivitz)-253.4(AJ,)-254.6(Soo)-247.9(Y,)-245.5(et)-249.6(al.)]TJ 1.6781 -1.2624 TD [(Long)-11(-te)-8.9(rm)-502.1(ef)]TJ /F12 1 Tf 5.4501 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(ca)-8.7(cy)-501.8(and)-512.7(saf)-11.6(ety)-509.7(pro)]TJ /F12 1 Tf 8.4285 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(le)-505.7(of)-509.2(ril)-10.4(onac)-10.9(ept)-508.1(in)-506.7(the)-512.3(treatm)-12.7(ent)-509.8(of)]TJ -14.9444 -1.2699 TD [(cryopryin-associated)-411.7(periodic)-410.2(syndromes:)-409.3(results)-413.4(of)-403.3(a)-402.1(72-week)-409.1(open-label)]TJ 0 -1.2624 TD 0.0401 Tc [(e)-5(x)1.6(te)-5(nsion)-545.2(s)3.5(t)-5.6(udy.)]TJ /F16 1 Tf 7.8918 0 TD 0.0395 Tc [(Clin)-548.3(Ther)]TJ /F11 1 Tf 4.9361 0 TD 0.0423 Tc [(\(2012)7.3(\))-544.5(3)-0.3(4)7.3(\()-0.2(10\):209)7.3(1)]TJ /F13 1 Tf 8.5796 0 TD 0 Tc ()Tj /F11 1 Tf 0.5518 0 TD 0.0434 Tc [(103.)-532.3(do)6.7(i:)-539.9(10)8.4(.10)8.4(16/)]TJ -21.9593 -1.2699 TD 0 Tc (j.clinthera.2012.09.009)Tj -1.6781 -1.2624 TD [(96.)-502.1(Goldbach-Mansky)-252.2(R,)-241.4(Shrof)60.1(f)-245.7(SD,)-240.4(Wilson)-246.5(M,)-242.5(Snyder)-249.1(C,)-244.7(Plehn)-247.4(S,)-243.8(Barham)-245.2(B.)-242.2(A)]TJ 1.6781 -1.2699 TD [(pilot)-231.6(study)-224.7(to)-233.6(evaluate)-226.1(the)-232.6(safety)-226.5(and)-233(ef)]TJ /F12 1 Tf 15.2997 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(cacy)-230.8(of)-229.5(the)-225(long-acting)-230.1(interleukin-1)]TJ -15.8289 -1.2699 TD [(in)-15.4(hi)-10.3(bi)-11(t)-7.9(o)0(r)-511.8(r)0(i)-18.5(lon)-16.7(ac)-8.7(ep)-16.4(t)-506.8(\()0(I)-11.9(n)-10.8(ter)-14.1(le)-14.3(uk)-11.5(in)-15.4(-1)-512.5(Tr)-12.2(a)-9(p)0(\))-512.8(i)-12.1(n)-509.7(p)-9.1(at)-9.3(ie)-11.9(nt)-11.2(s)-512.9(wit)-15.8(h)-512.2(f)0(a)-12.8(m)0(i)-8.9(l)0(i)-11.6(a)-9(l)-513.5(col)-13.2(d)]TJ 0 -1.2624 TD [(auto)-9.8(in)]TJ /F12 1 Tf 2.5701 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(amm)-10.2(atory)-509.1(syndrome.)]TJ /F16 1 Tf 9.3431 0 TD [(Arthr)-11.3(itis)-503.1(Rheu)-12(matol)]TJ /F11 1 Tf 8.7081 0 TD [(\(2)-9.5(008\))-502.8(58\(8\):2)-14.7(432)]TJ /F13 1 Tf 7.3853 0 TD ()Tj /F11 1 Tf 0.514 0 TD (42.)Tj -29.0498 -1.2699 TD [(doi:)-301.1(10.1002/art.23620)]TJ -1.6781 -1.2624 TD [(97.)-502.1(Wike)]TJ /F20 1 Tf 3.772 0.0378 TD ()Tj /F11 1 Tf 0.0454 -0.0378 TD [(n)-252.7(M)0(,)-250.1(Halle)]TJ /F20 1 Tf 4.218 0.0378 TD ()Tj /F11 1 Tf 0.0454 -0.0378 TD [(n)-252.7(B)0(,)-249.7(Kullenberg)-260.3(T,)-248.9(Koskinen)-259.5(LO.)-250.6(Development)-256.4(and)-255.7(ef)64.5(fect)-253.1(of)]TJ -6.4026 -1.2699 TD [(antibodies)-337.2(to)-339.4(anakinra)-334(during)-338(treatment)-341.1(of)-335.3(severe)-332.6(CAPS:)-341.9(sub-analysis)-336.5(of)-335.3(a)]TJ 0 -1.2624 TD [(long-term)-334.4(safety)-332.3(and)-331.3(ef)]TJ /F12 1 Tf 9.4036 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(cacy)-329.1(study.)]TJ /F16 1 Tf 4.7698 0 TD [(Clin)-330.6(Rheumatol)]TJ /F11 1 Tf 6.6369 0 TD [(\(2018\))-330.9(37\(12\):3381)]TJ /F13 1 Tf 7.6725 0 TD ()Tj /F11 1 Tf 0.514 0 TD (6.)Tj -29.5336 -1.2699 TD [(doi:)-301.1(10.1007/s10067-018-4196-x)]TJ -1.6781 -1.2699 TD [(98.)-502.1(Connolly)-355.7(M,)-355.9(Marrelli)-349.4(A,)-357.4(Blades)-355.4(M,)-348.3(McCormick)-357.3(J,)-359.5(Maderna)-353.4(P,)-353.9(Godson)-351.7(C,)]TJ 1.6781 -1.2624 TD 0.023 Tc [(et)-521.6(al.)-522.5(A)-0.6(cute)-521(serum)-518.1(a)-1.1(myloid)-515.3(A)-522.1(i)-4.2(ndu)]TJ 15.9498 0 TD [(ces)-520(migrat)7.6(ion,)-522.4(angiogenesis,)-522.4(a)6.5(nd)]TJ -15.9498 -1.2699 TD 0.0197 Tc (in)Tj /F12 1 Tf 7.4999 0 0 7.4999 329.4991 236.9196 Tm 0 Tc ()Tj /F11 1 Tf 0.5443 0 TD 0.0171 Tc [(a)-7(m)5.2(matio)-4.5(n)-515.3(in)-515.3(syno)-4.5(vial)-519.1(c)-5.3(e)2.2(ll)-5(s)-518.4(i)5(n)-522.9(v)-1.1(itro)-518.5(and)-513.6(i)-2.6(n)-522.9(a)-513.5(human)-515.3(r)-4.4(heu)-7.2(m)5.2(a)-7(t)1.6(oid)]TJ -1.3833 -1.2624 TD 0 Tc [(arthritis/SCID)-362.8(mouse)-351.2(chimera)-354.6(model.)]TJ /F16 1 Tf 15.6852 0 TD [(J)-353.2(Immunol)]TJ /F11 1 Tf 4.6791 0 TD [(\(2010\))-353.6(184\(11\):6427)]TJ /F13 1 Tf 8.179 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (37.)Tj -29.0498 -1.2699 TD [(doi:)-301.1(10.4049/jimmunol.0902941)]TJ -1.6781 -1.2624 TD [(9)-12.3(9)0(.)-512.5(I)0(s)-13.6(h)0(i)-10.3(i)-511(W,)-522.4(Ma)-16(t)-7.9(sud)-17.1(a)-515.5(M)0(,)-514.7(N)-9.4(a)-9(k)0(a)-11.3(m)0(u)-13.5(r)0(a)-521.9(A)-8.4(,)-515.2(N)0(a)-10.8(k)0(a)-11.3(m)-11.9(ura)-523.4(N)-9.3(,)-507.7(Su)-17.4(zu)-16.5(ki)-520.9(A,)-516.1(Ik)-17.1(eda)-524.3(S.)]TJ 1.7008 -1.2699 TD [(Abd)-16.5(om)-18.4(ina)-16.8(l)-513.5(f)-11.4(at)-515.8(a)-9(s)0(p)-15.5(i)0(r)-11(a)-9(t)-7.9(i)0(o)-11(n)-509.7(bi)-18.6(op)-15.6(sy)-516(a)-9(n)0(d)-518.9(g)-10.7(en)-10.6(ot)-14.4(yp)-12.2(i)-12.1(n)0(g)-520.4(o)0(f)-516.7(s)0(e)-13.7(r)0(u)-15.5(m)-510.9(a)-9(m)0(y)-15(l)0(o)-13.5(i)0(d)-520.2(A)]TJ T* [(con)-17(tri)-11.3(bu)-15.6(te)-514.1(t)-7.9(o)-505.4(ea)-16.3(rly)-523(dia)-15.1(gn)-13.9(osi)-9.9(s)-512.9(o)0(f)-516.7(r)0(e)-13.7(a)0(c)-8.7(t)-7.9(ive)-521.4(A)-8.4(A)-507.3(a)-9(myl)-14.5(oi)-11(d)-9.1(osi)-9.8(s)-512.9(s)0(e)-13.7(c)0(o)-13.8(n)0(d)-12.4(ary)-517.4(t)-7.9(o)]TJ 0 -1.2624 TD 0.0295 Tc [(rheumatoid)-531.5(a)5.4(r)0.4(thritis.)]TJ /F16 1 Tf 9.7135 0 TD [(Intern)-528(Med)]TJ /F11 1 Tf 5.5484 0 TD 0.0278 Tc [(\(20)-7.2(03\))-536.3(42\(9)-7.2(\))0.4(:800)]TJ /F13 1 Tf 7.3475 0 TD 0 Tc ()Tj /F11 1 Tf 0.5443 0 TD 0.0282 Tc [(5.)-532.4(doi:)-532.4(10.216)-6.8(9/)]TJ -23.1537 -1.2699 TD 0 Tc (internalmedicine)Tj -2.298 -1.2624 TD [(100.)-499.3(Migita)-376.3(K,)-370.8(Eguchi)-374.9(K,)-370.8(Tsukada)-375.9(T,)-377.5(Kawabe)-374.4(Y,)-366.5(Takashima)-381.2(H,)-367.5(Mine)-377.4(M,)-371(et)-370.5(al.)]TJ 2.1544 -1.2699 TD [(Increased)-418.5(circulating)-409.7(serum)-411.6(amyloid)-414(A)-401.5(protein)-415.4(derivatives)-416.5(in)-408.5(rheumatoid)]TJ 0 -1.2624 TD [(arthritis)-232.7(patients)-236.9(with)-233.2(secondary)-232.2(amyloidosis.)]TJ /F16 1 Tf 18.2327 0 TD [(Lab)-232(Invest)]TJ /F11 1 Tf 4.2936 0 TD [(\(1996\))-232.6(75\(3\):371)]TJ /F13 1 Tf 6.6143 0 TD ()Tj /F11 1 Tf 0.514 0 TD (5.)Tj -31.8089 -1.2699 TD [(101.)-499.3(Gorlier)-411.1(C,)-411(Sellam)-413.3(J,)-412.4(Laurans)-411.7(L,)-415.1(Simon)-404.8(T,)-415.2(Giurgea)-412.4(I,)-409(Bastard)-417.3(JP,)-409.8(et)-408.3(al.)-410.3(In)]TJ 2.1544 -1.2699 TD [(familial)-276.1(Mediterranean)-276.8(fever,)-278.6(soluble)-276.5(TREM-1)-271.5(plasma)-279.2(level)-273.6(is)-275.5(higher)-274.7(in)-272.4(case)]TJ 0 -1.2624 TD 0.0437 Tc [(of)-542.2(amylo)7(i)1.3(do)7(sis.)]TJ /F16 1 Tf 7.408 0 TD 0.0438 Tc [(I)6.4(nnate)-536.3(Imm)8.4(u)0.3(n)]TJ /F11 1 Tf 7.0829 0 TD 0.0429 Tc [(\(20)7.9(19\))-543.9(25\(8)7.9(\))0.4(:487)]TJ /F13 1 Tf 7.5516 0 TD 0 Tc ()Tj /F11 1 Tf 0.5518 0 TD 0.0431 Tc [(9)8.1(0)0.5(.)-540.2(d)-3.8(o)6.4(i)0.7(:)-540.2(10.11)8.1(77/)]TJ -22.5943 -1.2699 TD 0 Tc (1753425919870847)Tj -2.1544 -1.2624 TD [(102.)-499.3(L)24.5(a)21.2(c)22.9(h)24.5(m)25.8(a)21.2(n)19.4(n)-214.9(H)19.2(J)27.2(,)-228(G)27.7(o)23.8(o)23.8(d)21.1(m)25.8(a)21.2(n)-222.5(H)26.8(J)19.6(B)23.6(,)-220.4(G)27.7(i)18.1(l)23.2(b)23.8(e)30.5(r)16.3(t)29.9(s)23.8(o)23.8(n)-222.5(J)19.6(A)21.8(,)-220.4(G)27.7(a)21.2(l)23.2(l)23.2(i)25.7(m)25.8(o)23.8(r)23.8(e)-226.5(J)27.2(R)24.4(,)-228(S)22(a)28.8(b)23.8(i)25.7(n)-222.5(C)21(A)21.8(,)-220.4(G)27.7(i)18.1(l)23.2(l)23.2(m)25.8(o)23.8(r)23.8(e)]TJ 2.1544 -1.2699 TD -0.0237 Tc [(JD,)-221.5(e)-0.8(t)-228.2(a)-2.5(l.)-221.5(Natural)-219.7(h)0.8(i)-5.6(s)0.1(to)7.6(r)-7.4(y)-223.3(and)-221.8(o)0.1(utcome)-227.6(in)-223.5(systemic)-227.5(AA)-221.1(amyloi)-5.6(dosi)-5.6(s.)]TJ /F16 1 Tf 25.3458 0 TD 0.2017 Tc [(NE)224.6(n)226.2(g)224.6(lJM)222.5(e)226.3(d)]TJ /F11 1 Tf -25.3458 -1.2624 TD -0.0252 Tc [(\(2)-7.3(007\))-302(3)-7.3(56\(23)-7.3(\):2361)]TJ /F13 1 Tf 7.6952 0 TD 0 Tc ()Tj /F11 1 Tf 0.4838 0 TD -0.0193 Tc 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[(110.)-499.3(Shi)-230.1(F,)-229.6(Wu)-227.9(T,)-226.3(Zhu)-230.7(X,)-225.5(Ge)-229.1(Y,)-222.8(Zeng)-229.5(X,)-233.1(Chi)-223.6(Y,)-230.4(et)-226.9(al.)-228.9(Association)-229.5(of)-229.5(viral)-226.6(load)-228.1(with)]TJ 2.1544 -1.2624 TD [(s)-14(e)0(r)-13.7(u)-9.1(m)-518.4(b)-14(io)-11(m)-11.9(a)-9(k)-9.9(e)0(r)-21.3(s)-512.9(a)-9(m)-11.9(on)-17.3(g)-517.1(C)-9.2(O)-9.4(V)0(I)-20.7(D)0(-)-13.1(1)-12.3(9)-518.8(c)0(a)-16.3(s)0(e)-21.3(s)0(.)]TJ /F16 1 Tf 18.8903 0 TD 0.0127 Tc [(Vir)12.7(o)-1.9(lo)12.7(gy)]TJ /F11 1 Tf 3.9156 0 TD 0.0125 Tc [(\()12.5(2)-4.6(0)12.5(2)-4.6(0\))-498.7(54)12.5(6:12)12.5(2)]TJ /F13 1 Tf 6.3194 0 TD 0 Tc ()Tj /F11 1 Tf 0.514 0 TD 0.0123 Tc (6.)Tj -29.6394 -1.2699 TD 0 Tc [(doi:)-301.1(10.1016/j.virol.2020.04.011)]TJ -2.1544 -1.2624 TD [(111.)-499.3(Wang)-339.9(D,)-330.5(Li)-335.3(R,)-332.1(Wang)-332.4(J,)-336.9(Jiang)-332.9(Q,)-335.6(Gao)-327.9(C,)-335.5(Yang)-335.2(J,)-329.3(et)-340.3(al.)-327.1(Correlation)-338.5(analysis)]TJ 2.1544 -1.2699 TD [(between)-307.4(disease)-307.1(severity)-310.7(and)-301.1(clinical)-307(and)-308.6(biochemical)-304.4(characteristics)-315.1(of)-305.1(143)]TJ 0 -1.2624 TD [(cases)-338.8(of)-342.9(COVID-19)-341.6(in)-332.9(Wuhan,)-345.3(China:)-342.8(a)-334(descriptive)-345.3(study.)]TJ /F16 1 Tf 24.091 0 TD [(BMC)-339.4(Infect)-341.4(Dis)]TJ /F11 1 Tf -24.091 -1.2699 TD [(\(2020\))-300.7(20\(1\):519.)-305.1(doi:)-301.1(10.1186/s12879-020-05242-w)]TJ -2.1544 -1.2699 TD [(112.)-499.3(Li)-312.6(H,)-314.6(Xiang)-319.8(X,)-308.7(Ren)-318.8(H,)-314.6(Xu)-316.6(L,)-309.3(Zhao)-312.6(L,)-316.8(Chen)-312.7(X,)-316.2(et)-310(al.)-319.6(Serum)-315.1(Amyloid)-315.2(A)-310.8(i)0(s)-313.3(a)]TJ 2.1544 -1.2624 TD [(biomarker)-423.7(of)-418.5(severe)-415.8(Coronavirus)-418.1(Disease)-423.1(and)-414.4(poor)-421.5(prognosis.)]TJ /F16 1 Tf 26.1395 0 TD [(J)-421.2(Infection)]TJ /F11 1 Tf -26.1395 -1.2699 TD [(\(2020\))-300.7(80\(6\):646)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(55.)-305.6(doi:)-301.1(10.1016/j.jinf.2020.03.035)]TJ -9.3507 -1.2624 TD [(113.)-499.3(Li)-252.2(X,)-255.7(Wang)-249.2(L,)-256.4(Yan)-249(S,)-251.3(Yang)-252.1(F,)-252.2(Xiang)-259.3(L,)-248.8(Zhu)-253.3(J,)-253.7(et)-249.6(al.)-251.5(Clinical)-256(characteristics)-254.6(of)]TJ 2.1544 -1.2699 TD [(25)-243.9(death)-250.7(cases)-248(with)-240.7(COVID-19:)-244.5(A)-250.3(retrospective)-246.3(review)-243.7(of)-244.6(medical)-252.8(records)-245.9(in)]TJ 0 -1.2624 TD [(a)-371.8(single)-371.8(medical)-373.7(center,)-373.3(Wuhan,)-375.6(China.)]TJ /F16 1 Tf 16.6075 0 TD [(Int)-368.5(J)-368.3(Infect)-371.6(Dis)]TJ /F11 1 Tf 6.4631 0 TD [(\(2020\))-376.3(94:128)]TJ /F13 1 Tf 5.5938 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (32.)Tj -29.1708 -1.2699 TD [(doi:)-301.1(10.1016/j.ijid.2020.03.053)]TJ -2.1544 -1.2699 TD [(114.)-499.3(Mo)-240.2(XN,)-250(Su)-236.6(ZQ,)-249.1(Lei)-236.8(CL,)-242.9(Chen)-244.7(DF,)-241.4(Peng)-245.4(H,)-239(Chen)-244.7(RC,)-243(et)-242(al.)-244(Serum)-247.1(amyloid)-240.2(A)]TJ 2.1544 -1.2624 TD [(is)-343.6(a)-334(predictor)-344.3(for)-341.7(prognosis)-339.4(of)-342.9(COVID-19.)]TJ /F16 1 Tf 17.6128 0 TD (Respirology)Tj /F11 1 Tf 4.8076 0 TD [(\(2020\))-338.5(25\(7\):764)]TJ /F13 1 Tf 6.7201 0 TD ()Tj /F11 1 Tf 0.514 0 TD (5.)Tj -29.6546 -1.2699 TD [(doi:)-301.1(10.1111/resp.13840)]TJ -2.1544 -1.2624 TD [(115.)-499.3(Watson)-289.6(G,)-291(See)-287.4(CG,)-292.7(Woo)-284.6(P.)-285.8(Use)-290.1(of)-290(somatic)-287.9(cell)-293.2(hybrids)-291.2(and)]TJ /F12 1 Tf 26.5099 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(uorescence)-294.9(in)]TJ -24.8847 -1.2699 TD [(situ)-232.1(hybridization)-237.1(to)-233.6(localize)-237.4(the)-232.6(functional)-235.5(serum)-230.2(amyloid)-240.2(A)-227.7(\(SAA\))-238.6(genes)-231.5(to)]TJ 0 -1.2624 TD [(chromosome)-235.1(11p15.4-p15.1)-234.1(and)-233(the)-232.6(entire)-233.3(SAA)-236.7(superfamily)-236.5(to)-233.6(chromosome)]TJ 0 -1.2699 TD (11p15.)Tj /F16 1 Tf 7.4999 0 0 7.4999 83.6787 265.4362 Tm (Genomics)Tj /F11 1 Tf 4.1349 0 TD [(\(1994\))-300.7(23\(3\):694)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(6.)-300.8(doi:)-301.1(10.1006/geno.1994.1559)]TJ -16.4412 -1.2699 TD [(116.)-499.3(Jumeau)-412.4(C,)-403.5(Awad)-407.8(F,)-403.4(Assrawi)-414.9(E,)-406.8(Cobret)-406.6(L,)-400(Duquesnoy)-408.3(P,)-406.8(Giurgea)-412.4(I,)-409(et)-400.7(al.)]TJ 2.1544 -1.2624 TD [(Expression)-320.1(of)-312.6(SAA1,)-318.3(SAA2)-317.1(and)-308.6(SAA4)-317.1(genes)-314.6(in)-317.8(human)-311.1(primary)-322.6(monocytes)]TJ 0 -1.2699 TD 0.0135 Tc [(and)-517.2(m)1.6(onocyte-)4.7(derived)-509.7(m)-6(acrophages.)]TJ /F16 1 Tf 16.1841 0 TD 0 Tc [(Pl)-25.4(oS)-540.5(O)-13.6(n)-13.3(e)]TJ /F11 1 Tf 4.4599 0 TD 0.0125 Tc [(\(2019\))-513.8(14\()-7.3(5\):e)12.5(0)-7.1(2)-7.4(17005.)]TJ -20.644 -1.2624 TD 0 Tc [(doi:)-301.1(10.1371/journal.pone.0217005)]TJ -2.1544 -1.2699 TD [(117.)-499.3(Kluve-Beckerman)-217(B,)-204.4(Drumm)-209.9(ML,)-210.4(Benson)-207.1(MD.)-208.9(Nonexpression)-213(of)-206.8(the)-209.9(human)]TJ 2.1544 -1.2624 TD [(serum)-373.8(amyloid)-368.7(A)-363.7(three)-374.8(\(SAA3\))-371.9(gene.)]TJ /F16 1 Tf 15.7079 0 TD [(DNA)-368.9(Cell)-369.1(Biol)]TJ /F11 1 Tf 6.1985 0 TD [(\(1991\))-376.3(10\(9\):651)]TJ /F13 1 Tf 6.7579 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (61.)Tj -29.1708 -1.2699 TD [(doi:)-301.1(10.1089/dna.1991.10.651)]TJ -2.1544 -1.2699 TD [(118.)-499.3(Steel)-415.7(DM,)-420.6(Sellar)-415.3(GC,)-421.2(Uhlar)-417.8(CM,)-410.5(Simon)-420(S,)-417.6(deBeer)-422(FC,)-412.6(Whitehead)-419(AS.)-418.5(A)]TJ 2.1544 -1.2624 TD [(constitutively)-327.9(expressed)-324.6(serum)-328.4(amyloid)-323.3(A)-318.4(protein)-324.7(gene)-323.3(is)-328.5(closely)-324.3(linked)-320.9(to,)]TJ 0 -1.2699 TD [(and)-444.7(shares)-449.4(structural)-447(similarities)-451(with,)-446(an)-443.1(acute)-441.3(phase)-445.7(serum)-449.4(amyloid)-444.3(A)]TJ 0 -1.2624 TD [(protein)-302(gene.)]TJ /F16 1 Tf 5.5635 0 TD (Genomics)Tj /F11 1 Tf 4.1273 0 TD [(\(1993\))-308.2(16\(2\):447)]TJ /F13 1 Tf 6.6899 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(54.)-305.6(doi:)-301.1(10.1006/geno.1993.1209)]TJ -19.0415 -1.2699 TD [(119.)-499.3(Blank)-368.4(N,)-358.3(Hegenbart)-371.7(U,)-360.7(Lohse)-364.1(P,)-361.4(Beimler)-368.6(J,)-359.5(Rcken)-365.1(C,)-365.7(Ho)-357.7(AD,)-369.2(et)-363(al.)-357.4(Risk)]TJ 2.1544 -1.2624 TD 0.0227 Tc [(factors)-520.4(f)-3.8(or)-520.4(AA)-522.4(am)-4.4(yloi)-4.5(dosi)-4.5(s)-520.4(i)3(n)-524.8(G)-2.5(erm)-4.4(a)6.1(ny.)]TJ /F16 1 Tf 18.5804 0 TD 0.0168 Tc [(Am)-11(y)-7.3(l)-1.2(o)-6.5(i)-8(d)]TJ /F11 1 Tf 4.029 0 TD 0.021 Tc [(\()-6.4(2)1.1(0)-6.5(15\))-528(22)-6.5(:\(1\))-6.4(:1)]TJ /F13 1 Tf 6.4858 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.0199 Tc (7.)Tj -29.6319 -1.2699 TD 0 Tc [(doi:)-301.1(10.3109/13506129.2014.980942)]TJ -2.1544 -1.2699 TD [(120.)-499.3(Booth)-275(DR,)-275.9(Booth)-275(SE,)-278.9(Gillmore)-280(JD,)-273.1(Hawkins)-281.8(PN,)-272.5(Pepys)-280.3(MB.)-271.8(SAA1)-279.3(alleles)-277.8(as)]TJ 2.1544 -1.2624 TD [(risk)-238.9(factors)-243.8(in)-234.6(reactive)-241.9(systemic)-236.4(AA)-243.6(amyloidosis.)]TJ /F16 1 Tf 19.4119 0 TD (Amyloid)Tj /F11 1 Tf 3.5906 0 TD [(\(1998\))-232.7(5\(4\):262)]TJ /F13 1 Tf 6.138 0 TD ()Tj /F11 1 Tf 0.514 0 TD (5.)Tj -29.6546 -1.2699 TD [(doi:)-301.1(10.3109/13506129809007299)]TJ -2.1544 -1.2624 TD [(121.)-499.3(Utku)-242.8(U,)-239.8(Dilek)-244.7(M,)-235(Akpolat)-246.8(I,)-235.1(Bedir)-245.7(A,)-236.4(Akpolat)-246.8(T.)-233.8(SAA1)-241.5(alpha/alpha)-249(alleles)-240(in)]TJ 2.1544 -1.2699 TD 0.0142 Tc [(Be)14.2(h)-6.4(c)-0.7(e)14.2(t)]TJ /F13 1 Tf 2.7364 0 TD 0 Tc ()Tj /F11 1 Tf 0.2268 0 TD 0.0138 Tc [(s)-514.2(d)4.7(is)13.8(e)-7.5(a)4.8(se)-507.5(rel)13.8(a)-2.2(te)13.8(d)-516.7(a)-2.7(myl)13.8(o)-7.2(idosi)13.8(s.)]TJ /F16 1 Tf 13.1454 0 TD 0.0106 Tc [(Cl)-7.4(in)-509.1(Rheumato)-5.2(l)]TJ /F11 1 Tf 7.1434 0 TD 0.012 Tc [(\(2007\))-506.7(26:927)]TJ /F13 1 Tf 5.8659 0 TD 0 Tc ()Tj /F11 1 Tf 0.5216 0 TD 0.0123 Tc (9.)Tj -29.6394 -1.2624 TD 0 Tc [(doi:)-301.1(10.1007/s10067-006-0435-7)]TJ 32.6177 84.8666 TD [(122.)-499.3(M)23.3(o)23.8(r)23.8(i)25.7(g)19.6(u)21.1(c)22.9(h)24.5(i)-193.6(M)23.3(,)-205.3(T)24.4(e)22.9(r)23.8(a)28.8(i)-201.1(C)21(,)-197.8(K)23.5(o)23.8(s)23.8(e)22.9(k)20.3(i)-201.1(Y)27.8(,)-197.8(U)18.4(e)22.9(s)23.8(a)28.8(t)22.3(o)-203(M)30.8(,)-205.3(N)28.4(a)21.2(k)20.3(a)28.8(j)23.2(i)18.1(m)25.8(a)-198(A)21.8(,)-197.7(I)23.1(n)27(a)21.2(d)21.1(a)-198(S)22(,)-197.7(e)22.9(t)-196.9(a)21.2(l)23.2(.)-197.8(I)23.1(n)]TJ /F12 1 Tf 29.7831 0 TD ()Tj /F11 1 Tf 0.5065 0 TD -0.0211 Tc [(ue)9.4(nce)]TJ -28.1352 -1.2699 TD -0.025 Tc [(of)-217.8(g)-5.4(e)-2.1(notyp)-3.9(e)-2.1(s)-220.4(a)-3.8(t)-214.3(S)-3(A)-3.2(A)4.4(1)-218.8(a)-3.8(nd)-223.1(SA)-3.2(A2)-218.8(loci)-218.6(on)-217.2(the)-221.3(d)3.7(ev)-5.4(elopm)-6.7(e)-2.1(nt)-221.9(an)-5.6(d)-215.6(t)-2.7(he)-221.3(leng)-5.4(th)-219.7(of)-217.8(la)-3.8(tent)]TJ 0 -1.2624 TD -0.0237 Tc [(period)-252.1(of)-254.3(secondar)-7.4(y)-246(AA-)5.3(amyloidosis)-249.3(i)-5.6(n)-246.2(p)-2.6(atients)-249.3(w)-4.3(ith)-248.6(r)0.1(heumatoid)-252.1(a)-2.5(rt)6.2(hr)-7.4(itis.)]TJ /F16 1 Tf 28.3468 0 TD -0.0227 Tc (Hum)Tj -28.3468 -1.2699 TD -0.0193 Tc [(Ge)5.3(n)5.2(e)5.3(t)]TJ /F11 1 Tf 2.487 0 TD -0.0251 Tc [(\(1999)-7.2(\))-302(105\()-7.1(4)0.3(\):360)]TJ /F13 1 Tf 6.7806 0 TD 0 Tc ()Tj /F11 1 Tf 0.4838 0 TD -0.0253 Tc [(6.)-306.2(doi)-7.2(:)-298.6(10.10)-7.4(0)0.1(7/)-5.7(s0043)-7.4(9)0.2(9900)-7.4(150)]TJ -11.9057 -1.2624 TD 0 Tc [(123.)-499.3(Ajiro)-327.7(J,)-321.7(Narita)-325.9(I,)-325.9(Sato)-326.4(F,)-327.8(Saga)-324.1(D,)-322.9(Hasegawa)-330.2(H,)-322.2(Kuroda)-326.6(T,)-332.1(et)-325.1(al.)-319.6(SAA1)-324.7(gene)]TJ 2.1544 -1.2699 TD [(polymorphisms)-381.9(and)-384.2(the)-376.2(risk)-382.5(of)-380.7(AA)-379.7(amyloidosis)-384.9(in)-378.2(Japanese)-379.4(patients)-388.1(with)]TJ T* [(rheu)-13.4(matoi)-9.6(d)-500.5(arthr)-12.7(itis.)]TJ /F16 1 Tf 9.1088 0 TD [(Mod)-507.9(Rheuma)-11.9(tol)]TJ /F11 1 Tf 7.1812 0 TD [(\(2006\))-512.3(16\(5\):2)-14.7(94)]TJ /F13 1 Tf 6.9091 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(9.)-504.9(doi:)-505.1(10)-9.6(.3109/)]TJ -23.7131 -1.2624 TD (s10165-006-0500-8)Tj -2.1544 -1.2699 TD 0.0152 Tc [(124.)-500(N)5.8(aka)6.2(m)-4.3(u)6.1(r)1.2(a)-515.4(T)1.8(,)-515.2(H)-3.4(ig)4.5(ashi)-511(S,)-515.2(Tomod)6.1(a)-515.4(K,)-515.2(Tsuk)5.3(ano)-512.8(M)0.7(,)-507.6(B)1(aba)-515.4(S)-0.6(,)-507.6(S)-0.6(hono)-512.8(M.)]TJ 2.2148 -1.2624 TD 0.0464 Tc (Signi)Tj /F12 1 Tf 2.2224 0 TD 0 Tc ()Tj /F11 1 Tf 0.5745 0 TD 0.0477 Tc [(cance)-549.2(o)3.4(f)-545.7(S)-5.9(AA1.3)-546.7(allele)-549.2(genotype)-549.2(in)-545.2(Japanese)-549.2(patients)-548.3(wi)5.3(th)]TJ -2.7969 -1.2699 TD 0 Tc [(amyloidosis)-332(secondary)-338(to)-331.9(rheumatoid)-334.5(arthritis.)]TJ /F16 1 Tf 19.2834 0 TD [(Rheumatol)-333.3(\(Oxford\))]TJ /F11 1 Tf 8.3982 0 TD (\(2006\))Tj -27.6816 -1.2624 TD (45\(1\):43)Tj /F13 1 Tf 3.2958 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(9.)-300.8(doi:)-301.1(10.1093/rheumatology/kei112)]TJ -6.0246 -1.2699 TD [(125.)-499.3(Moriguchi)-265.9(M,)-257.6(Terai)-259.9(C,)-252.3(Kaneko)-261.9(H,)-261.7(Koseki)-260.6(Y,)-253.1(Kajiyama)-264.4(H,)-254.1(Uesato)-260.5(M,)-257.6(et)-257.1(al.)-259.1(A)]TJ 2.1544 -1.2699 TD [(novel)-412.6(single-nucleotide)-419.8(polymorphism)-413.3(at)-410(the)-406.4(50-)]TJ /F12 1 Tf 20.2056 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(anking)-411(region)-416.6(of)-410.9(SAA1)]TJ -20.7348 -1.2624 TD [(a)-9(s)0(s)-12.8(o)-14(ci)-11.9(a)-9(t)-7.9(ed)-522.9(w)-10.9(i)0(t)-12.5(h)-512.2(r)-14(i)0(s)-11(k)-516.4(of)-524.3(t)-7.9(y)-10.7(p)-9.1(e)-513.8(A)-8.4(A)-514.9(a)-9(m)0(y)-15(l)0(o)-13.5(i)0(d)-13.7(o)0(s)-20.4(i)0(s)-517.4(s)-14(ec)-14.6(on)-17.3(d)-9.1(a)0(r)-15.4(y)-509.6(t)-7.9(o)-520.5(rh)-12.1(eu)-16.5(m)-12(a)0(t)-9.3(o)-14(id)]TJ 0 -1.2699 TD 0.0108 Tc [(ar)10.8(t)-3.5(h)10.8(r)-8.9(i)10.8(ti)10.8(s)-7.7(.)]TJ /F16 1 Tf 3.9912 0 TD 0.0089 Tc [(A)8.9(r)-6.7(th)8.9(ritis)-504.7(R)8.9(h)-6.8(e)8.9(u)-10(m)8.9(a)-6.1(t)1(o)8.9(l)]TJ /F11 1 Tf 8.8291 0 TD 0 Tc [(\()-12.3(2)0(0)-9.6(0)-12.3(1\))-523.5(44)-9.6(\()-12.3(6)0(\))-17.1(:)-8.8(12)-9.6(6)-12.3(6)]TJ /F13 1 Tf 7.4911 0 TD ()Tj /F11 1 Tf 0.5216 0 TD [(72)-9.6(.)-515.2(d)-9.1(oi)-18.6(:)-515.2(1)0(0)-9.6(.)-8.8(1)-12.3(0)0(0)-9.6(2)-12.4(/1)-15.4(52)-17.1(9-)]TJ -20.833 -1.2624 TD (0131\(200106\)44:6<1266::AID-ART218>3.0.CO;2-3)Tj -2.1544 -1.2699 TD [(126.)-499.3(Yamada)-284.8(T,)-286.7(Okuda)-280.8(Y,)-283.3(Takasugi)-283.7(K,)-287.7(Wang)-279.5(L,)-286.6(Marks)-280.5(D,)-285.1(Benson)-282.7(MD,)-284.5(et)-279.8(al.)-281.8(An)]TJ 2.1544 -1.2624 TD [(allele)-233.6(of)-229.5(serum)-237.7(amyloid)-232.6(A1)-232.4(associated)-232.2(with)-233.2(amyloidosis)-233.7(in)-234.6(both)-230.6(Japanese)-235.8(and)]TJ 0 -1.2699 TD (Caucasians.)Tj /F16 1 Tf 4.9588 0 TD (Amyloid)Tj /F11 1 Tf 3.6511 0 TD [(\(2003\))-300.7(10\(1\):7)]TJ /F13 1 Tf 5.7298 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(11.)-305.6(doi:)-301.1(10.3109/13506120308995250)]TJ -17.0005 -1.2699 TD [(127.)-499.3(M)23.3(o)23.8(r)23.8(i)25.7(g)19.6(u)21.1(c)22.9(h)24.5(i)-223.8(M)23.3(,)-235.5(K)23.5(a)28.8(n)19.4(e)22.9(k)27.9(o)-233.2(H)26.8(,)-228(T)24.4(e)22.9(r)23.8(a)21.2(i)-231.3(C)28.6(,)-235.6(K)23.5(o)23.8(s)23.8(e)22.9(k)27.9(i)-231.3(Y)27.8(,)-235.5(K)23.5(a)28.8(j)23.2(i)18.1(y)27.1(a)21.2(m)25.8(a)-228.2(H)19.2(,)-228(I)23.1(n)27(a)21.2(d)21.1(a)-228.2(S)22(,)-228(e)22.9(t)-227.1(a)21.2(l)30.8(.)-235.5(R)24.4(e)22.9(l)23.2(a)28.8(t)22.3(i)25.7(v)19.6(e)]TJ 2.1544 -1.2624 TD -0.0243 Tc [(transcri)-6.2(ptional)-311(a)-3.1(ctivi)-6.2(t)5.6(i)-6.2(e)-1.4(s)-302.8(o)-0.5(f)-307.8(S)-2.3(AA1)-308.8(pr)-8(omoters)-302.8(p)-3.2(olym)-6(orph)-7.3(i)1.4(c)-311.3(a)4.5(t)-311.9(p)4.4(osi)-6.2(tion)-307.2(-13\(T)-7.5(/)2.9(C\):)]TJ 0 -1.2699 TD -0.0234 Tc [(potential)-302.5(a)-2.2(ssociat)6.5(i)-5.3(on)-298.8(between)-306.3(inc)7.1(r)-7.1(e)7.1(a)]TJ 13.7425 0 TD -0.0238 Tc [(sed)-305.1(t)-1.5(ranscription)-306.8(and)-305.1(a)5(m)-5.5(y)3.3(loidosis.)]TJ /F16 1 Tf 13.3948 0 TD -0.0218 Tc [(Amyl)5.5(oid)]TJ /F11 1 Tf -27.1374 -1.2624 TD -0.025 Tc [(\(2)-7.1(005\))-301.8(1)-7.1(2:26)]TJ /F13 1 Tf 4.7774 0 TD 0 Tc ()Tj /F11 1 Tf 0.4838 0 TD -0.0253 Tc [(3)-7.4(2)0.2(.)-298.6(d)-4.2(oi:)-306.2(1)0.2(0.1080)-7.4(/13)-7.4(50612)-7.4(0500)-7.4(03239)-7.4(4)]TJ 7.4999 0 0 7.4999 306.1417 483.9306 Tm 0 Tc [(128.)-499.3(Thorn)-420.7(CF,)-420.2(Lu)-423(ZY,)-416(Whitehead)-419(AS.)-426.1(Regulation)-418.9(of)-418.5(the)-421.6(human)-417(acute)-426.2(phase)]TJ 2.1544 -1.2624 TD [(serum)-313.3(amyloid)-308.2(A)-310.8(genes)-314.6(by)-304.4(tumour)-315.6(necrosis)-312.6(factor-alpha,)-309.9(interleukin-6)-318.6(and)]TJ 0 -1.2699 TD [(glucocorticoids)-318.7(in)-317.8(hepatic)-315.5(and)-316.2(epithelial)-318.9(cell)-315.9(lines.)]TJ /F16 1 Tf 20.4702 0 TD [(Scand)-315.4(J)-315.4(Immunol)]TJ /F11 1 Tf 7.2719 0 TD (\(2004\))Tj -27.7421 -1.2699 TD (59:152)Tj /F13 1 Tf 2.6155 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(8.)-300.8(doi:)-301.1(10.1111/j.0300-9475.2004.01369.x)]TJ -5.2838 -1.2624 TD [(129.)-499.3(H)19.2(a)28.8(g)19.6(i)25.7(h)24.5(a)21.2(r)23.8(a)-160.2(K)23.5(,)-160(N)28.4(i)18.1(s)23.8(h)24.5(i)25.7(k)20.3(a)28.8(w)19.4(a)-160.2(T)24.4(,)-160(S)29.6(u)21.1(g)19.6(a)28.8(m)18.3(a)28.8(t)22.3(a)-160.2(Y)20.3(,)-152.4(S)22(o)23.8(n)19.4(g)-154.3(J)19.6(,)-160(I)]TJ 19.873 0 TD -0.0239 Tc [(sobe)-182.4(T,)-183.9(Taga)-184.1(T,)-183.9(et)-183(al.)-176.3(E)-6.2(ssential)-182.1(role)]TJ -17.7187 -1.2699 TD -0.0235 Tc [(of)-186(STAT3)-187(i)-5.4(n)-185.5(c)-0.6(ytokine-driven)-185.5(NF-)]TJ /F17 1 Tf 12.4802 0 TD 0 Tc (k)Tj /F11 1 Tf 0.514 0 TD -0.0236 Tc [(B-mediated)-183.9(serum)-186.7(a)-2.4(myloid)-183.9(A)-190.8(g)-4(e)6.9(n)-4.2(e)-189.7(e)-0.7(xpressi)-5.5(on.)]TJ /F16 1 Tf -12.9942 -1.2624 TD -0.0193 Tc [(Ge)5.3(n)5.2(e)5.3(s)-268.4(C)8.5(e)5.3(l)0.5(l)8(s)]TJ /F11 1 Tf 4.4675 0 TD -0.0255 Tc [(\(2)-7.6(005\))-272.1(1)0(0)-7.6(\(11\))-7.5(:)3.5(1)-7.6(051)]TJ /F13 1 Tf 7.2039 0 TD 0 Tc ()Tj /F11 1 Tf 0.4913 0 TD -0.0248 Tc [(63.)-275.5(d)3.9(oi)-6.7(:)-267.9(1)0.6(0.11)-6.9(11/)-5.2(j.1)-6.9(3)0.6(65-2443)-6.9(.)4.2(2)-6.9(005.00)-6.9(900.x)]TJ -14.317 -1.2699 TD 0 Tc [(130.)-499.3(Migita)-232.7(K,)-227.2(Koga)-229.4(T,)-233.8(Komori)-224(A,)-228.9(Torigoshi)-238.5(T,)-226.3(Maeda)-230.4(Y,)-230.4(Izumi)-229.1(Y,)-230.4(et)-226.9(al.)-228.9(In)]TJ /F12 1 Tf 29.6621 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (uence)Tj -28.0369 -1.2624 TD [(of)-433.6(Janus)-431.4(kinase)-433.5(inhibition)-436.8(on)-425.5(interleukin)-433.5(6-mediated)-435.2(induction)-441.1(of)-426(acute-)]TJ 0 -1.2699 TD [(phase)-392.8(serum)-388.9(amyloid)-391.4(A)-386.4(i)0(n)-393.3(rheumatoid)-387.5(synovium.)]TJ /F16 1 Tf 20.9993 0 TD [(J)-391(Rheumatol)]TJ /F11 1 Tf 5.3972 0 TD [(\(2011\))-391.4(38)]TJ -26.3966 -1.2699 TD (\(11\):2309)Tj /F13 1 Tf 3.7796 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(17.)-298(doi:)-301.1(10.3899/jrheum.101362)]TJ -6.448 -1.2624 TD [(131.)-499.3(Hagihara)-345(K,)-340.6(Nishikawa)-349(T,)-339.7(Isobe)-343.7(T,)-347.2(Song)-338.5(J,)-344.4(Sugamata)-347(Y,)-343.8(Yoshizaki)-343.5(K.)-340.6(IL-6)]TJ 2.1544 -1.2699 TD [(plays)-291.6(a)-288.7(critical)-295.9(role)-291.7(in)-287.5(the)-293.1(synergistic)-294.6(induction)-289.9(of)-290(human)-296(serum)-290.6(amyloid)-293.1(A)]TJ 0 -1.2624 TD [(\(SAA\))-374.7(gene)-376.3(when)-374.9(stimulated)-382.7(with)-369.2(proin)]TJ /F12 1 Tf 16.547 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-375.7(cytokines)-373.7(as)-378.2(analyzed)]TJ -17.0761 -1.2699 TD [(with)-278.5(an)-284.4(SAA)-274.5(isoform)-280.3(real-time)-281.9(quantitative)-289.3(RT-PCR)-274.8(assay)-283.3(system.)]TJ /F16 1 Tf 26.9786 0 TD (Biochem)Tj -26.9786 -1.2624 TD [(Biophys)-302.3(Res)-304.2(Commun)]TJ /F11 1 Tf 9.0181 0 TD [(\(2004\))-300.7(314\(2\):363)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(9.)-300.8(doi:)-301.1(10.1016/j.bbrc.2003.12.096)]TJ -18.845 -1.2699 TD [(132.)-499.3(Yoshizaki)-222.6(K.)-227.2(Pathogenic)-218.3(Role)-223.2(of)-221.9(IL-6)-223(Combined)-217.1(with)-225.6(TNF-alfa)-220.7(or)-224.5(IL-1)-215.4(in)-227(the)]TJ 2.1544 -1.2699 TD [(Induction)-292.5(of)-290(Acute)-289.6(Phase)-290.3(Proteins)-289.1(SAA)-289.7(and)-285.9(CRP)-292.1(in)-287.5(Chronic)-284.8(In)]TJ /F12 1 Tf 25.6936 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (ammatory)Tj -26.2227 -1.2624 TD (Diseases.)Tj /F16 1 Tf 3.9686 0 TD [(Adv)-395(Exp)-398.3(Med)-391.9(Biol)]TJ /F11 1 Tf 7.9976 0 TD [(\(2011\))-399(691:141)]TJ /F13 1 Tf 6.0927 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(50.)-396.3(doi:)-391.8(10.1007/978-1-4419-)]TJ -18.5728 -1.2699 TD (6612-4_15)Tj -2.1544 -1.2624 TD [(133.)-499.3(Kushner)-211.2(I,)-204.9(Jiang)-211.9(SL,)-204.1(Zhang)-206.6(D,)-209.5(Lozanski)-203.7(G,)-207.9(Samols)-207.7(D.)-202(Do)-207.2(post-transcriptional)]TJ 2.1544 -1.2699 TD [(m)-11.9(e)-14.9(ch)-20.6(a)-9(n)-10.8(i)-12.1(s)-14(m)-11.9(s)-520.4(p)-16.7(a)-9(r)-14(t)-7.9(i)-12.1(c)0(i)-19.4(p)-16.7(a)-9(t)-7.9(e)-528.9(i)0(n)-529.4(i)-12.1(n)-10.8(d)-16.7(u)-9.1(c)0(t)-22.8(i)-12.1(on)-531.3(o)-14(f)-517.8(C)-16.8(-)-8.8(r)-14(e)0(a)-16.3(c)-14.9(t)-7.9(i)-12.1(v)-10.7(e)-528.9(p)-9.1(r)-14(ot)-21.9(ei)-19.4(n)-524.8(a)-9(n)-10.8(d)-523.2(s)-14(e)0(r)-21.3(u)-9.1(m)]TJ 0 -1.2624 TD 0.0295 Tc [(amy)3.7(l)-0.2(o)7.9(i)-5.3(d)-523.9(A)-523.2(by)-525.4(IL)8.7(-6)-527.1(a)5.4(n)3.6(d)-531.5(I)7.2(L-1?)]TJ /F16 1 Tf 13.924 0 TD 0.026 Tc [(Ann)-531.5(N)-2.7(Y)-526.5(A)1.7(c)-7.2(a)1(d)-532.3(S)0.2(ci)]TJ /F11 1 Tf 8.5796 0 TD 0.0278 Tc [(\(1995\))-528.7(762:102)]TJ /F13 1 Tf 6.584 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.0275 Tc (7.)Tj -29.6243 -1.2699 TD 0 Tc [(doi:)-301.1(10.1111/j.1749-6632.1995.tb32318.x)]TJ -2.1544 -1.2699 TD [(134.)-499.3(Steel)-241.9(DM,)-246.7(Roger)-240.8(JT,)-236.9(DeBeer)-243.3(MC,)-244.2(DeBeer)-243.3(FC,)-238.8(Whitehead)-245.2(AS.)-244.6(Biosynthesis)-242.5(of)]TJ 2.1544 -1.2624 TD [(human)-273.3(acute-phase)-276(serum)-275.5(amyloid)-278(A)-273(protein)-271.8(\(A-SAA\))-271(in)-272.4(vitro:)-279.1(the)-270.4(roles)-275.5(or)]TJ 0 -1.2699 TD [(mRNA)-360.6(accumulation,)-357.8(poly)-350.7(\(A\))-358(tail)-353.5(shortening)-356.7(and)-354(translational)-359.3(ef)]TJ /F12 1 Tf 27.092 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (ciency.)Tj /F16 1 Tf -27.6211 -1.2624 TD [(Biochem)-302.7(J)]TJ /F11 1 Tf 4.286 0 TD [(\(1993\))-308.2(291\(Pt)-296.5(3\):701)]TJ /F13 1 Tf 8.3302 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(7.)-300.8(doi:)-301.1(10.1042/bj2910701)]TJ -15.2846 -1.2699 TD [(135.)-499.3(Lozanski)-362.5(G,)-359.1(Jiang)-363.1(SL,)-355.3(Samols)-358.9(D.)-360.7(Kushner)-362.4(I.)-356.1(C-reactive)-365.7(protein)-355(and)-361.5(serum)]TJ 2.1544 -1.2624 TD [(amyloid)-202.4(A)-205(mRNA)-201.9(stability)-200.6(following)-203.7(induction)-206.8(by)-198.5(cytokines.)]TJ /F16 1 Tf 24.0457 0 TD (Cytokine)Tj /F11 1 Tf 3.704 0 TD (\(1996\))Tj -27.7496 -1.2699 TD (8\(7\):534)Tj /F13 1 Tf 3.3033 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(40.)-298(doi:)-301.1(10.1006/cyto.1996.0072)]TJ -5.9717 -1.2699 TD [(136.)-499.3(Tanaka)-507.1(F,)-501.7(Migita)-504.8(K,)-506.9(Kawabe)-502.9(Y,)-502.5(Aoyagi)-503.3(T,)-506(Ida)-501.5(H,)-503.6(Kawakami)-501.9(A,)-508.5(et)-499(al.)]TJ 2.1544 -1.2624 TD [(Interleukin-18)-424.2(induces)-409.9(serum)-419.1(amyloid)-414(A)-409.1(\(SAA\))-420(protein)-415.4(production)-417.5(from)]TJ 0 -1.2699 TD 0.0341 Tc [(rh)5.7(eum)7(a)2.4(t)3.5(o)-2.6(i)6.9(d)-534.4(s)5(y)0.8(no)5(vial)]TJ /F12 1 Tf 9.5699 0 TD 0 Tc ()Tj /F11 1 Tf 0.5669 0 TD 0.0299 Tc [(br)-6.7(oblas)-6.7(ts.)]TJ /F16 1 Tf 4.6489 0 TD 0.033 Tc [(Life)-532(Sci)-528.5(F)1.2(eb)]TJ /F11 1 Tf 5.881 0 TD 0.0346 Tc [(\()7.2(2)-0.4(0)7.1(04\))-529.5(1)7.1(3)-0.4(\()7.2(74\))7.2(:16)7.1(7)-0.4(1)]TJ /F13 1 Tf 8.4133 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.035 Tc (9.)Tj -29.6168 -1.2624 TD 0 Tc [(doi:)-308.6(10.1016/j.lfs.2003.08.025)]TJ -2.1544 -1.2699 TD [(137.)-499.3(Thorn)-382.9(CF,)-382.4(Whitehead)-381.2(AS.)-380.7(Dif)55.4(ferential)-381.6(glucocorticoid)-380.4(enhancement)-391(of)-380.7(the)]TJ 2.1544 -1.2624 TD [(cytokine-driven)-326.7(transcriptional)-325.3(activation)-320.1(of)-312.6(the)-323.3(human)-318.7(acute)-320.3(phase)-317.2(serum)]TJ 0 -1.2699 TD [(a)-9(m)-11.9(y)-10.7(l)-14.6(oi)-18.6(d)-523.2(A)-514.9(g)-10.7(e)-14.9(n)-10.8(e)0(s)-21.3(,)-522.8(SA)-16.7(A)-16(1)-518.8(a)-9(n)-10.8(d)-523.2(S)0(A)-16.7(A)-16(2.)]TJ /F16 1 Tf 16.033 0 TD [(J)-13(I)0(m)-19.9(m)-12.7(un)-19(ol)]TJ /F11 1 Tf 4.5733 0 TD [(\()-12.3(2)0(0)-17.1(0)-12.4(2\))-531.1(1\()-17.1(1)-12.3(6)-12.3(9)0(\))-17.1(:)-16.3(39)-17.1(9)]TJ /F13 1 Tf 7.5365 0 TD ()Tj /F11 1 Tf 0.5216 0 TD [(40)-17.1(6)-12.3(.)]TJ 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[(cy)-18(t)-15.5(o)0(s)-20.4(k)-9.9(e)-14.9(l)-14.6(et)-22.8(a)-9(l)-521(r)-14(e)-14.9(a)-9(r)-14(r)-14(a)-9(n)-10.8(g)-10.7(e)-14.9(m)-11.9(en)-25.7(t)-7.9(,)-522.8(c)-14.9(e)0(l)-21.9(l)-521(m)-11.9(a)-16.6(t)-7.9(r)-14(i)-12.1(x)-522.3(i)-12.1(n)-10.8(t)-15.5(e)0(r)-21.3(a)-9(c)-14.9(t)-7.9(i)-12.1(o)-14(n)-10.8(s)-528(a)-9(n)-10.8(d)-523.2(p)-16.7(ro)-20.4(m)-11.9(o)-14(t)-7.9(e)-14.9(s)-520.4(c)-14.9(el)-21.9(l)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT /F6 1 Tf 6.9999 0 0 6.9999 45.3543 744.2644 Tm (Soric)Tj /F10 1 Tf 1.6198 0.0324 TD ()Tj /F6 1 Tf 0.8585 -0.0324 TD [(Hosman)-304.8(et)-300.5(al.)]TJ 51.9802 0 TD [(SAA)-295.6(in)-304.4(In)]TJ /F7 1 Tf 3.9281 0 TD ()Tj /F6 1 Tf 0.4374 0 TD [(ammatory)-307.2(Rheumatic)-303.5(Diseases)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.5958 0 TD 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[(149.)-499.3(Cheng)-330.9(N,)-335.6(He)-328.3(R,)-332.1(Tian)-332.6(J,)-329.3(Ye)-334.8(PP,)-328.6(Ye)-334.8(RD.)-328.8(Cutting)-332.3(edge:)-338(TLR2)-332.1(is)-328.4(a)-334(functional)]TJ 2.1544 -1.2699 TD [(receptor)-337.9(for)-326.6(acute-phase)-336.5(serum)-336(amyloid)-330.9(A.)]TJ /F16 1 Tf 17.7867 0 TD [(J)-330.5(Immunol)]TJ /F11 1 Tf 4.6413 0 TD [(\(2008\))-330.9(181\(1\):22)]TJ /F13 1 Tf 6.7125 0 TD ()Tj /F11 1 Tf 0.514 0 TD (6.)Tj -29.6546 -1.2699 TD [(doi:)-301.1(10.4049/jimmunol.181.1.22)]TJ -2.1544 -1.2624 TD [(150.)-499.3(Connolly)-355.7(M,)-348.3(Rooney)-349.9(PR,)-352.1(McGarry)-351.6(T,)-354.8(Maratha)-348.7(AX,)-354.9(McCormick)-349.7(J,)-352(Miggin)]TJ 2.1544 -1.2699 TD [(SM,)-485.1(et)-476.3(al.)-478.3(Acute)-478.5(serum)-479.6(amyloid)-482.1(A)-477.1(i)0(s)-479.6(a)0(n)-480.9(endogenous)-485.1(TLR2)-475.7(ligand)-482(that)]TJ 0 -1.2624 TD [(mediates)-252.5(in)]TJ /F12 1 Tf 4.5808 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-247.1(and)-248.2(angiogenic)-248.4(mechanisms.)]TJ /F16 1 Tf 16.0708 0 TD [(Ann)-247.4(Rheum)-243.9(Dis)]TJ /F11 1 Tf 6.5689 0 TD (\(2016\))Tj -27.7496 -1.2699 TD (75\(7\):1392)Tj /F13 1 Tf 4.2634 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(8.)-300.8(doi:)-308.6(10.1136/annrheumdis-2015-207655)]TJ -6.9242 -1.2624 TD [(151.)-499.3(O)]TJ /F13 1 Tf 2.8952 0 TD ()Tj /F11 1 Tf 0.2192 0 TD [(Reilly)-246.5(S,)-251.3(Cant)-248.6(R,)-249(Ciechomska)-259.2(M,)-242.5(Finnigan)-251.8(J,)-253.7(Oakley)-249.8(F,)-252.2(Hambleton)-251.8(S,)-243.8(et)-249.6(al.)]TJ -0.96 -1.2699 TD [(Serum)-375.6(amyloid)-376.2(A)-371.3(induces)-372.1(interleukin-6)-379(in)-370.7(dermal)]TJ /F12 1 Tf 20.954 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(broblasts)-372.4(via)-371.9(Toll-like)]TJ -21.4831 -1.2699 TD [(receptor)-262.3(2,)-247.9(interleukin-1)-265.6(receptor-associated)-261.5(kinase)-252.1(4)-254.2(and)-255.7(nuclear)-261(factor-)]TJ /F17 1 Tf 29.0045 0 TD (k)Tj /F11 1 Tf 7.4999 0 0 7.4999 283.1244 322.4125 Tm (B.)Tj /F16 1 Tf -29.5487 -1.2624 TD (Immunology)Tj /F11 1 Tf 5.2914 0 TD [(\(2014\))-300.7(143\(3\):331)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(40.)-305.6(doi:)-301.1(10.1111/imm.12260)]TJ -15.1183 -1.2699 TD [(152.)-499.3(Okamoto)-265.1(H,)-261.7(Katagiri)-255.4(Y,)-260.6(Kiire)-263.9(A,)-259.1(Momohara)-266(S,)-258.9(Kamatani)-257.9(N.)-267.6(Serum)-262.2(amyloid)]TJ 2.1544 -1.2624 TD 0.0223 Tc [(A)-522.8(a)5.8(ct)6.8(iva)5.7(t)-0.7(es)-513.2(nucl)7.7(ear)-513.2(f)3.4(act)6.8(o)0.7(r-)5.9(ka)5.7(pp)5.6(aB)-513.5(in)-517.7(rheu)5.6(ma)5.8(to)8.3(id)-523.5(synovial)]TJ /F12 1 Tf 26.0564 0 TD 0 Tc ()Tj /F11 1 Tf 0.5518 0 TD 0.0211 Tc [(bro)7.1(b)-0.5(lasts)]TJ -26.6082 -1.2699 TD 0.0448 Tc [(through)-543(b)0.5(inding)-547.9(to)-536.2(r)-7(e)7.3(ceptor)-543.7(o)0.5(f)-541.1(a)-2(d)5.4(v)-3.7(anced)-546.4(glycation)-540.5(e)-0.3(nd)5.4(-produ)5.4(cts.)]TJ /F16 1 Tf 0 -1.2624 TD 0 Tc [(J)-300.3(Rheumatol)]TJ /F11 1 Tf 5.2234 0 TD [(\(2008\))-308.2(35\(5\):752)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (6.)Tj -14.574 -1.2699 TD [(153.)-499.3(M)23.3(u)21.1(l)23.2(l)23.2(a)28.8(n)-267.8(R)16.8(H)26.8(,)-265.8(B)23.6(r)23.8(e)22.9(s)23.8(n)19.4(i)25.7(h)24.5(a)21.2(n)-267.8(B)23.6(,)-265.8(G)20.1(o)23.8(l)23.2(d)28.7(e)22.9(n)19.4(-)21.4(M)30.8(a)21.2(s)23.8(o)23.8(n)-267.8(L)24.5(,)-273.3(M)23.3(a)28.8(r)23.8(k)20.3(h)24.5(a)21.2(m)-269(T)24.4(,)-265.8(O)]TJ /F13 1 Tf 25.0586 0 TD ()Tj /F11 1 Tf 0.189 0 TD -0.0232 Tc [(Hara)-289.2(R,)-289(FitzGerald)]TJ -23.0932 -1.2699 TD -0.022 Tc [(O,)-355.8(et)-362.5(a)6.8(l)1.2(.)-355.8(A)-0.2(cute-)7(p)-0.9(hase)-354.4(s)-5.7(e)8.5(r)-5.7(u)6.7(m)-359(a)-0.8(myl)8.8(o)1.8(id)-356.2(A)-355.5(s)1.8(ti)]TJ 16.5848 0 TD -0.0233 Tc [(m)-5(u)-2.2(l)7.5(a)-2.1(tion)-359.2(of)-359.7(angioge)7.2(n)-3.9(esis,)-364.7(l)7.5(eukocyte)]TJ -16.5848 -1.2624 TD -0.0228 Tc [(recruitment,)-394.4(and)-402.3(m)3(at)7.1(rix)-393.9(d)-1.7(egrada)6(tion)-396.5(in)]TJ 15.8213 0 TD -0.0238 Tc [(rheumatoid)-395.8(arthritis)-400.6(t)-1.5(hrough)-399.9(an)-397.5(NF-)]TJ -15.8213 -1.2699 TD -0.0232 Tc [(kap)5.5(p)-2.1(aB-)5.8(d)-2.1(ependent)-318.4(signal)-309.9(transduc)7.3(tion)-313.7(p)5.5(a)-2(thway.)]TJ /F16 1 Tf 18.7618 0 TD -0.0227 Tc [(A)5.9(r)1.1(thr)-6.4(i)5.4(tis)-309.6(R)3.4(heumato)6.9(l)]TJ /F11 1 Tf 7.8766 0 TD -0.0179 Tc [(\(2)7.6(0)7.6(0)7.5(6\))-302.3(54)]TJ -26.6384 -1.2624 TD -0.0247 Tc [(\()-6.7(1\):105)]TJ /F13 1 Tf 2.6533 0 TD 0 Tc ()Tj /F11 1 Tf 0.4913 0 TD -0.0256 Tc [(14.)-306.5(doi)-7.5(:)-298.9(10)-7.7(.1)-7.7(002/)-6(art.215)-7.7(18)]TJ -5.299 -1.2699 TD 0 Tc [(154.)-499.3(Migita)-346(K,)-340.6(Kawabe)-344.2(Y,)-343.8(Tominaga)-340.4(M,)-340.8(Origuchi)-344.9(T,)-347.2(Aoyagi)-337(T,)-347.2(Eguchi)-344.7(K,)-340.6(et)-340.3(al.)]TJ 2.1544 -1.2624 TD [(Serum)-322.7(amyloid)-323.3(A)-318.4(protein)-317.2(induces)-326.8(production)-319.2(of)-320.2(matrix)-320.2(metalloproteinases)]TJ 0 -1.2699 TD [(by)-304.4(human)-303.6(synovial)]TJ /F12 1 Tf 7.9749 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (broblasts.)Tj /F16 1 Tf 4.1046 0 TD [(Lab)-300.1(Invest)]TJ /F11 1 Tf 4.4297 0 TD [(\(1998\))-308.2(78\(5\):535)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (9.)Tj -26.389 -1.2699 TD [(155.)-499.3(Vallon)-310.8(R,)-301.9(Freuler)-309.7(F,)-305.2(Desta-Tesdu)-315.8(N,)-305.4(Robeva)-302.7(A,)-312(Dawson)-304.8(J,)-306.6(Wenner)-306.8(P,)-308.5(et)-302.5(al.)]TJ 2.1544 -1.2624 TD [(Se)-15.5(ru)-15.5(m)-518.4(a)-9(my)-15(lo)-13.5(id)-520.2(A)-514.9(\()0(a)-13.7(p)-9.1(oS)-14.7(A)-8.4(A)-8.4(\))-511.2(ex)-15.5(p)-9.1(r)0(e)-13.7(s)0(s)-20.4(i)0(o)-11(n)-517.3(is)-517.4(u)-9.1(p)-9.1(-)-8.8(re)-13.7(g)-10.7(u)0(l)-8.6(a)-9(t)-7.9(e)0(d)-522.9(i)-12.1(n)-509.7(r)0(h)-19.7(eum)-20.8(a)-9(t)-7.9(oi)-11(d)]TJ 0 -1.2699 TD 0.0521 Tc [(arthri)-5.4(t)6.4(i)-5.4(s)-551.5(a)-2.2(nd)-554.2(induces)-551.5(transcription)-555.9(o)0.3(f)-548.9(m)-5.2(atri)-5.4(x)-545.7(m)-5.2(etalloproteinases.)]TJ /F16 1 Tf 0 -1.2624 TD 0 Tc [(J)-300.3(Immunol)]TJ /F11 1 Tf 4.5808 0 TD [(\(2001\))-300.7(166\(4\):2801)]TJ /F13 1 Tf 7.6423 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(7.)-300.8(doi:)-301.1(10.4049/jimmunol.166.4.2801)]TJ -14.8915 -1.2699 TD [(156.)-499.3(O)]TJ /F13 1 Tf 2.8952 0 TD ()Tj /F11 1 Tf 0.2192 0 TD [(Hara)-405.8(R,)-407.7(Murphy)-403.3(EP,)-404.2(Whitehead)-411.5(AS,)-403.4(FitzGerald)-410.5(O,)-403.6(Bresnihan)-407.7(B.)-408.5(Local)]TJ -0.96 -1.2624 TD [(expression)-262(of)-252.2(the)-255.3(serum)-260.4(amyloid)-255.3(A)-257.9(and)-255.7(formyl)-257.9(peptide)-258.6(receptor-like)-254.6(1)-254.2(genes)]TJ 0 -1.2699 TD [(in)-295.1(synovial)-299.9(tissue)-291.2(is)-298.2(associated)-300.2(with)-293.6(matrix)-297.5(metalloproteinase)-298.2(production)-296.5(in)]TJ T* [(patients)-221.8(with)-218(in)]TJ /F12 1 Tf 6.1531 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-216.9(arthritis.)]TJ /F16 1 Tf 7.9598 0 TD [(Arthritis)-219.6(Rheumatol)]TJ /F11 1 Tf 8.1185 0 TD [(\(2004\))-217.5(50\(6\):1788)]TJ /F13 1 Tf 7.0829 0 TD ()Tj /F11 1 Tf -29.8435 -1.2624 TD [(99.)-305.6(doi:)-301.1(10.1002/art.20301)]TJ -2.1544 -1.2699 TD [(157.)-499.3(Kobayashi)-367.3(A,)-357.4(Naito)-362.3(S,)-357.2(Enomoto)-364.9(H,)-360(Shiomoi)-357.8(T,)-362.3(Kimura)-365.3(T,)-362.3(Obata)-359.2(K,)-363.3(et)-355.4(al.)]TJ 2.1544 -1.2624 TD [(Serum)-352.9(levels)-340.5(of)-350.4(matrix)-342.8(metalloproteinase)-351.1(3)-344.9(\(stromelysin)-347.6(1\))-349.7(for)-341.7(monitoring)]TJ 0 -1.2699 TD [(synovitis)-325.4(in)-310.2(rheumatoid)-327(arthritis.)]TJ /F16 1 Tf 13.6518 0 TD [(Arch)-317.4(Pathol)-320(Lab)-315.2(Med)]TJ /F11 1 Tf 9.0105 0 TD [(\(2007\))-315.8(131\(4\):563)]TJ /F13 1 Tf 7.1812 0 TD ()Tj /F11 1 Tf -29.8435 -1.2624 TD [(70.)-305.6(doi:)-301.1(10.1043/1543-2165\(2007\)131[563:SLOMMS]2.0.CO;2)]TJ 32.6177 84.8666 TD [(158.)-499.3(Satomura)-287.3(K,)-287.7(Torigoshi)-291.4(T,)-286.8(Koga)-282.3(T,)-286.7(Maeda)-290.8(Y,)-283.3(Izumi)-289.6(Y,)-290.9(Jiuchi)-283.8(Y,)-290.9(et)-287.4(al.)-281.8(\(SAA\))]TJ 2.1544 -1.2699 TD [(induces)-379.7(pentraxin)-369(3)-375.2(\(PTX3\))-370.2(production)-379.7(in)-370.7(rheumatoid)-372.3(synoviocytes.)]TJ /F16 1 Tf 28.5056 0 TD (Mod)Tj -28.5056 -1.2624 TD (Rheumatol)Tj /F11 1 Tf 4.6111 0 TD [(\(2013\))-308.2(23\(1\):28)]TJ /F13 1 Tf 6.2061 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(35.)-298(doi:)-301.1(10.3109/s10165-012-0630-0)]TJ -13.4855 -1.2699 TD [(159.)-499.3(Aggarwal)-276.1(S,)-281.6(Ghilardi)-275.7(N,)-275.1(Xie)-274(MH,)-276.2(de)-273.5(Sauvage)-283.2(FJ,)-270.4(Gurney)-281.2(AL.)-272.3(Interleukin-23)]TJ 2.1544 -1.2624 TD 0.0151 Tc [(pr)-6.4(om)-4.4(otes)-520.4(a)-515.5(d)-1.6(i)-4.6(s)1.1(t)-7.9(i)3(nct)-522(C)-1.7(D4)-518.8(T)-519.9(c)0.2(e)-7.3(l)0.5(l)-513.5(a)-1.4(c)-7.3(t)-0.4(ivati)-4.6(o)1.1(n)-517.3(s)-6.4(tate)-521.4(char)-6.4(acte)-7.3(ri)-4.6(zed)-523.2(by)-517.1(th)-5.7(e)]TJ 0 -1.2699 TD 0.0613 Tc [(production)-561.8(of)-562.4(inte)-6.5(rleukin)5.1(-)-0.4(17.)]TJ /F16 1 Tf 14.4758 0 TD 0.6203 Tc [(JB)557.3(i)557.7(o)559.2(lC)557.4(h)555.8(e)561.8(m)]TJ /F11 1 Tf 6.4102 0 TD 0.0577 Tc [(\(2)-7.6(00)-7.6(3\))-566.9(27)-7.6(8:)-11.5(191)-7.6(0)]TJ /F13 1 Tf 7.5894 0 TD 0 Tc ()Tj /F11 1 Tf 0.5745 0 TD 0.0653 Tc [(14)7.6(.)]TJ -29.0498 -1.2699 TD 0 Tc [(doi:)-301.1(10.1074/jbc.M207577200)]TJ -2.1544 -1.2624 TD [(160.)-499.3(Hirota)-317.5(K,)-310.3(Yoshitomi)-313.4(H,)-314.6(Hashimoto)-311.3(M,)-310.6(Maeda)-313.5(S,)-311.8(Teradaira)-316.1(S,)-311.8(Sugimoto)-314.8(N,)]TJ 2.1544 -1.2699 TD [(et)-355.4(al.)-349.8(Preferential)-362.4(recruitment)-359.1(of)-350.4(CCR6-)-355.3(expressing)-356.9(Th17)-353.7(cells)-352.5(to)-354.6(in)]TJ /F12 1 Tf 27.6287 0 TD ()Tj /F11 1 Tf 0.5367 0 TD (amed)Tj -28.1654 -1.2624 TD [(joints)-338(via)-341.7(CCL20)-336(in)-340.4(rheumatoid)-342.1(arthritis)-338.5(and)-338.9(its)-336.4(animal)-339.5(model.)]TJ /F16 1 Tf 26.0942 0 TD [(J)-338.1(Exp)-337.9(Med)]TJ /F11 1 Tf -26.0942 -1.2699 TD [(\(2007\))-300.7(204:2803)]TJ /F13 1 Tf 6.4782 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(12.)-298(doi:)-301.1(10.1084/jem.20071397)]TJ -9.1466 -1.2624 TD [(161.)-499.3(Migita)-255.3(K,)-257.4(Koga)-259.6(T,)-256.5(Torigoshi)-253.6(T,)-256.5(Maeda)-260.6(Y,)-253.1(Miyashita)-261.3(T,)-256.5(Izumi)-259.3(Y,)-253.1(et)-257.1(al.)-251.5(Serum)]TJ 2.1544 -1.2699 TD 0.0599 Tc [(am)10.2(yl)7.5(oid)-546.4(A)-553.3(pr)8.1(ot)6.6(ein)-555.7(s)8.1(timul)7.5(a)-2(t)6.6(e)-0.3(s)]TJ 14.4985 0 TD 0.0591 Tc [(C)4.5(C)4.5(L)0.5(20)-550.4(pr)7.3(od)4.6(uc)6.4(tio)7.3(n)-556.4(in)-548.9(rhe)6.4(u)-3(ma)4.7(t)5.8(o)-0.3(id)]TJ -14.4985 -1.2699 TD 0.0288 Tc (synoviocytes.)Tj /F16 1 Tf 6.1607 0 TD 0.0278 Tc [(Rheuma)-4.8(tol)-534.5(\()5.5(O)-8.4(x)4.5(f)-4.6(o)-3.1(rd)6.2(\))]TJ /F11 1 Tf 9.2751 0 TD [(\(2009)-7.2(\))-528.7(48\(7\):741)]TJ /F13 1 Tf 7.3399 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.0282 Tc [(7.)-524.8(doi:)-532.4(10.1093/)]TJ -23.3124 -1.2624 TD 0 Tc (rheumatology/kep089)Tj -2.1544 -1.2699 TD [(162.)-499.3(Lucherini)-258(M,)-257.6(Lopalco)-255.1(G,)-253.2(Cantarini)-253.7(L,)-256.4(Emmi)-252.6(G,)-253.2(Lopalco)-255.1(A,)-251.5(Venerito)-260.9(V,)-256.7(et)-249.6(al.)]TJ 2.1544 -1.2624 TD [(Critical)-222.2(regulation)-215.3(of)-214.4(Th17)-217.6(cell)-217.6(dif)65.6(ferentiation)-222.9(by)-213.7(serum)-222.6(amyloid-A)-212.1(signalling)]TJ 0 -1.2699 TD 0.0364 Tc [(in)-541.4(B)7.1(e)-1.1(hcet)]TJ /F13 1 Tf 4.2936 0 TD 0 Tc ()Tj /F11 1 Tf 0.2495 0 TD 0.5733 Tc [(sd)533.9(i)538.5(s)536.7(e)543.3(a)534.1(s)536.7(e)535.7(.)]TJ /F16 1 Tf 4.7547 0 TD 0.0365 Tc [(Immunol)-533.3(Lett)]TJ /F11 1 Tf 6.6596 0 TD 0.0353 Tc [(\(20)-7.3(18\))-536.4(201:38)]TJ /F13 1 Tf 7.4999 0 0 7.4999 488.3527 550.4314 Tm 0 Tc ()Tj /F11 1 Tf 0.5443 0 TD 0.0351 Tc [(44.)-540.6(doi:)-540.6(10.1016/)]TJ -22.685 -1.2624 TD 0 Tc (j.imlet.2018.10.013)Tj -2.1544 -1.2699 TD [(163.)-499.3(Metawi)-349(SA,)-342.9(Abbas)-339.1(D,)-345.6(Kamal)-346(MM,)-340.2(Ibrahim)-346(MK.)-347.5(Serum)-345.4(and)-338.9(synovial)]TJ /F12 1 Tf 30.6675 0 TD ()Tj /F11 1 Tf 0.5367 0 TD (uid)Tj -29.0498 -1.2699 TD [(levels)-340.5(of)-342.9(interleukin-17)-346(in)-340.4(correlation)-344.2(with)-339(disease)-344.9(activity)-342.3(in)-348(patients)-342.7(with)]TJ 0 -1.2624 TD (RA.)Tj /F16 1 Tf 1.8218 0 TD [(Clin)-300.4(Rheumatol)]TJ /F11 1 Tf 6.5765 0 TD [(\(2011\))-308.2(30\(9\):1201)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(7.)-300.8(doi:)-301.1(10.1007/s10067-011-1737-y)]TJ -18.2327 -1.2699 TD [(164.)-499.3(Shen)-266.4(H,)-269.2(Goodall)-266.8(JC,)-262.9(Hill)-263.9(Gaston)-269.9(JS.)-269.5(Frequency)-268.6(and)-263.3(phenotype)-271(of)-267.3(peripheral)]TJ 2.1544 -1.2624 TD [(blood)-209.4(Th17)-210.1(cells)-208.9(in)-211.9(ankylosing)-214.8(spondylitis)-211.6(and)-210.4(rheumatoid)-213.6(arthritis.)]TJ /F16 1 Tf 26.9786 0 TD (Arthritis)Tj -26.9786 -1.2699 TD (Rheumatol)Tj /F11 1 Tf 4.6111 0 TD [(\(2009\))-308.2(60\(6\):1647)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(56.)-298(doi:)-301.1(10.1002/art.24568)]TJ -14.4455 -1.2624 TD [(165.)-499.3(Romero-Sanchez)-267.6(C,)-259.9(Jaimes)-261.4(DA,)-263.3(Londoo)-259.9(J,)-261.3(De)-261(Avila)-258.9(J,)-261.3(Castellanos)-260.3(JE,)-258.6(Bello)]TJ 2.1544 -1.2699 TD [(JM.)-487.5(Association)-486.5(between)-481.3(Th-17)-483.5(cytokine)-488.2(pro)]TJ /F12 1 Tf 18.9735 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(le)-483(and)-482.5(clinical)-488.4(features)-488.1(in)]TJ -19.5026 -1.2699 TD [(patients)-304.9(with)-301.2(spondyloarthritis.)]TJ /F16 1 Tf 12.8808 0 TD [(Clin)-300.4(Exp)-300.1(Rheumatol)]TJ /F11 1 Tf 8.3755 0 TD [(\(2011\))-308.2(29\(5\):828)]TJ /F13 1 Tf 6.6898 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (34.)Tj -30.607 -1.2624 TD [(166.)-499.3(Bissonnette)-309.3(R,)-301.9(Nigen)-307.3(S,)-304.2(Langley)-310.6(RG,)-304.4(Lynde)-308.2(CW,)-304.8(Tan)-305.3(J,)-299.1(Fuentes-Duculan)-312.4(J,)]TJ 2.1544 -1.2699 TD [(et)-363(al.)-364.9(Increased)-365.6(expression)-367.8(of)-365.5(IL-17A)-364.7(and)-361.5(limited)-362.4(involvement)-367.6(of)-365.5(IL-23)-363.9(in)]TJ 0 -1.2624 TD [(patients)-274.7(with)-263.4(palmo-plantar)-277.9(\(PP\))-268.7(pustular)-275.8(psoriasis)-270.9(or)-269.9(PP)-266.9(pustulosis;)-270.3(results)]TJ 0 -1.2699 TD [(from)-255.4(a)-250.9(randomised)-255(controlled)-257.2(trial.)]TJ /F16 1 Tf 14.3019 0 TD [(J)-247.4(Eur)-253.8(Acad)-255.3(Dermatol)-256.2(Venereol)]TJ /F11 1 Tf 12.2307 0 TD [(\(2014\))-255.3(28)]TJ -26.5326 -1.2624 TD (\(10\):1298)Tj /F13 1 Tf 3.7796 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(305.)-302.8(doi:)-301.1(10.1111/jdv.12272)]TJ -6.448 -1.2699 TD [(167.)-484.2(Br)24.8(au)19.7(n)-260.3(J)0(,)-253.7(B)16.1(ar)22.4(al)29.4(ia)24.2(ko)29(s)-263.4(X)0(,)-255.7(D)0(e)26.3(o)16.2(dh)23(ar)-249.7(A,)-251.5(B)16.1(a)0(e)21.5(t)0(e)30.1(n)-267.8(D,)-247.3(Si)25(ep)21.4(e)15.4(r)-263.4(J,)-253.7(Em)28.5(er)24.1(y)-267.7(P)17.7(,)-265.8(e)15.4(t)-264.9(a)0(l)21.8(.)-258.2(Ef)82(f)18.9(e)0(c)23.2(t)-264.9(o)16.2(f)]TJ 2.1392 -1.2699 TD [(se)24.1(cu)21.3(ki)30.9(nu)25.4(ma)24.4(b)-240.8(o)0(n)-228.9(c)15.4(li)26.2(ni)22.4(c)15.4(a)0(l)-227.6(a)0(n)25.6(d)-243.5(r)16.3(a)0(d)19.7(i)18.1(og)28.2(ra)22.4(ph)23(i)18.1(c)-241.6(ou)22.2(tc)30.1(om)27(es)-232.9(i)18.1(n)-245.2(an)25.5(ky)24.8(l)15.7(o)16.2(si)19.3(n)19.4(g)-245(s)16.3(p)0(o)22.2(n)0(d)25.4(y)0(l)27.7(i)0(t)25.3(i)0(s)26.8(:)]TJ 0 -1.2624 TD 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0 TD [(\(2015\))-270.5(54\(4\):660)]TJ /F13 1 Tf 6.6596 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(5.)-270.6(doi:)-278.4(10.1093/rheumatology/keu359)]TJ -17.6053 -1.2624 TD [(170.)-499.3(Niemi)-226.7(K,)-227.2(Teiril)-226.1(L,)-218.6(Lappalainen)-235.1(J,)-223.5(Rajamki)-225(K,)-227.2(Baumann)-226(MH,)-223.3(rni)-226.5(K,)-227.2(et)-219.3(al.)]TJ 2.1544 -1.2699 TD [(Serum)-224.4(amyloid)-225.1(A)-220.1(activates)-228.8(the)-217.5(NLRP3)-227.1(in)]TJ /F12 1 Tf 16.2144 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammasome)-225.1(via)-228.3(P2X7)-216.1(receptor)-232.1(and)]TJ -16.7435 -1.2624 TD 0.019 Tc [(a)-519.1(c)-3.4(ath)5.7(e)-3.4(psin)-521(B)4.8(-)-5(sensitive)-525(p)2.3(athway.)]TJ /F16 1 Tf 14.7555 0 TD 0.0196 Tc [(J)-522.6(I)4.9(mmunol)]TJ /F11 1 Tf 5.1705 0 TD 0.0201 Tc [(\(201)7.8(1\))-521.3(186\(1)7.7(1)0.2(\):61)7.7(19)]TJ /F13 1 Tf 8.6779 0 TD 0 Tc ()Tj /F11 1 Tf 0.5291 0 TD 0.0199 Tc (28.)Tj -29.133 -1.2699 TD 0 Tc [(doi:)-301.1(10.4049/jimmunol.1002843)]TJ -2.1544 -1.2699 TD [(171.)-499.3(Husby)-383.8(G,)-374.2(Natvig)-377.2(JB,)-381.3(Sletten)-381.5(K.)-378.4(New,)-376.5(third)-381.4(class)-376.3(of)-380.7(amyloid)]TJ /F12 1 Tf 27.0996 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(bril)-379.7(protein.)]TJ /F16 1 Tf -25.4743 -1.2624 TD [(J)-300.3(Exp)-300.1(Med)]TJ /F11 1 Tf 4.4826 0 TD [(\(1974\))-300.7(139\(3\):773)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(8.)-300.8(doi:)-301.1(10.1084/jem.139.3.773)]TJ -14.317 -1.2699 TD [(17)-9.6(2.)-512.5(Mi)-19.1(git)-15.6(a)-515.5(K)0(,)-514.4(Y)-10(am)-13.4(asa)-16.8(ki)-520.9(S,)-515.9(Sh)-13.9(ib)-11(a)-9(t)-7.9(om)-10.8(i)-511(K)0(,)-522(I)0(d)-8.7(a)-515.5(H,)-518.7(Kaw)-19.1(ak)-11.3(a)-9(m)0(i)-515.4(M)0(,)-15.7(,)-507.7(E)-12.5(g)0(u)-12.2(c)0(h)-13(i)-511(K.)]TJ 2.177 -1.2624 TD [(Impai)-11.6(red)-506.6(degradati)-12.6(on)-501.1(of)-501.6(serum)-509.8(amy)-8.9(loid)-503.4(A)-499.8(\(SAA\))-510.7(protei)-11.6(n)-502.2(b)0(y)-500.9(cyto)-9.7(kine-)]TJ 0 -1.2699 TD 0.0579 Tc [(st)4.6(im)8.2(ulat)4.6(e)5.2(d)-556(mo)6.1(no)6.1(cy)9.4(te)5.2(s)6.1(.)]TJ /F16 1 Tf 10.923 0 TD 0.0564 Tc [(Clin)-554(E)3.7(x)2.8(p)-553.1(I)3.9(mmu)5.3(nol)]TJ /F11 1 Tf 9.26 0 TD 0.0573 Tc [(\(2)7.2(001)7.2(\))-552.2(1)-0.4(2)7.2(3)-0.4(\(3)7.2(\):40)7.1(8)]TJ /F13 1 Tf 8.2924 0 TD 0 Tc ()Tj /F11 1 Tf 0.5669 0 TD 0.0501 Tc [(11)-7.6(.)]TJ -29.0423 -1.2624 TD 0 Tc [(doi:)-301.1(10.1046/j.1365-2249.2001.01472.x)]TJ -2.177 -1.2699 TD [(173.)-499.3(Magy)-437.9(N,)-433.9(Benson)-433.9(MD,)-435.7(Liepnieks)-436.1(JL,)-440.8(Kluve-Beckerman)-436.2(B.)-438.7(Cellular)-432.4(events)]TJ 2.1544 -1.2699 TD [(associated)-436.3(with)-429.7(the)-429.1(initial)-426.4(phase)-438.2(of)-426(AA)-432.6(amyloidogenesis:)-429.8(insights)-435(from)-429.2(a)]TJ 0 -1.2624 TD 0.0222 Tc [(h)-6.2(u)-2.1(man)-525.3(m)-4.9(onoc)-7.8(yte)-529.4(m)-4.9(odel.)]TJ /F16 1 Tf 11.5353 0 TD 0.0237 Tc (Amyloid)Tj /F11 1 Tf 4.0441 0 TD 0.0275 Tc [(\()7.7(2)0(0)7.6(07\))-513.9(14)7.6(\(1\))7.7(:)3.6(51)]TJ /F13 1 Tf 6.7579 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.0266 Tc [(63)6.7(.)-518.9(d)-5.2(o)5(i)6.9(:)-526.4(1)6.7(0.1)6.7(0)-0.9(8)6.7(0)-0.9(/)]TJ -22.874 -1.2699 TD 0 Tc (13506120601116575)Tj -2.1544 -1.2624 TD [(174.)-499.3(Stix)-202.8(B,)-204.4(Khne)-198.3(T,)-203.6(Sletten)-207.7(K,)-197(Raynes)-208.8(J,)-200.8(Roessner)-200.5(A,)-206.2(Rcken)-198.8(C.)-206.9(Proteolysis)-203(of)-199.2(AA)]TJ 2.1544 -1.2699 TD (amyloid)Tj /F12 1 Tf 3.6889 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(bril)-447.7(proteins)-452.1(by)-448(matrix)-448.7(metalloproteinases-1,)-455.5(-2,)-445.7(and)-444.7(-3.)]TJ /F16 1 Tf 23.9323 0 TD [(Am)-452.8(J)]TJ -28.1503 -1.2624 TD (Pathol)Tj /F11 1 Tf 2.8649 0 TD [(\(2001\))-300.7(159\(2\):561)]TJ /F13 1 Tf 7.4999 0 0 7.4999 397.5306 141.959 Tm ()Tj /F11 1 Tf 0.5065 0 TD [(70.)-305.6(doi:)-301.1(10.1016/s0002-9440\(10\)61727-0)]TJ -12.6918 -1.2699 TD 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-1.2624 TD [(Re)20.4(s)-226.4(O)0(p)27(i)0(n)]TJ /F11 1 Tf 3.6889 0 TD [(\(2)20.7(0)17.9(1)0(7)20.7(\))-223.9(33)28.2(\(5)20.7(\))18(:)0(8)24.2(3)0(7)]TJ /F13 1 Tf 6.4253 0 TD ()Tj /F11 1 Tf 0.4989 0 TD [(43)28.2(.)-228(d)0(o)22.2(i)0(:)-217.4(1)17.9(0.)24.2(10)28.2(80)28.2(/0)22.4(30)28.2(07)20.7(9)17.9(9)0(5)28.2(.)0(2)24.2(0)0(1)28.2(7)0(.)24.2(1)0(2)28.2(8)0(9)20.7(9)17.9(08)]TJ -12.7523 -1.2699 TD [(190.)-499.3(O)]TJ /F13 1 Tf 2.8952 0 TD ()Tj /F11 1 Tf 0.2192 0 TD [(Neill)-367.8(L,)-362.2(Rooney)-365(P,)-361.4(Molloy)-369.6(D,)-360.7(Connolly)-363.2(M,)-363.5(McCormick)-372.4(J,)-359.5(McCarthy)-365.5(G,)]TJ -0.96 -1.2699 TD [(et)-226.9(al.)-221.3(Regulation)-222.3(of)-229.5(In)]TJ /F12 1 Tf 8.4814 0 TD ()Tj /F11 1 Tf 0.5367 0 TD [(ammation)-222.8(and)-225.5(Angiogenesis)-222.9(in)-227(Giant)-223.8(Cell)-219.5(Arteritis)-226.2(by)]TJ -9.0181 -1.2624 TD [(Acute-Phase)-309(Serum)-307.6(Amyloid)-307.7(A.)]TJ /F16 1 Tf 13.2058 0 TD [(Arthritis)-302.7(Rheumatol)]TJ /F11 1 Tf 8.2924 0 TD [(\(2015\))-300.7(67\(9\):2447)]TJ /F13 1 Tf 7.1661 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (56.)Tj -29.1708 -1.2699 TD [(doi:)-301.1(10.1002/art.39217)]TJ 32.6177 72.205 TD [(191.)-499.3(Chen)-403.4(ES,)-392.3(Song)-399(Z,)-398.5(Willett)-404.1(MH,)-397.2(Heine)-396.3(S,)-402.5(Yung)-395.9(RC,)-401.8(Liu)-397.4(MC,)-395.3(et)-400.7(al.)-395.2(Serum)]TJ 2.1544 -1.2699 TD [(amyloid)-444.3(A)-439.3(regulates)-441.5(granulomatous)-450.4(in)]TJ /F12 1 Tf 16.033 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammation)-442(in)-438.7(sarcoidosis)-451(through)]TJ -16.5621 -1.2624 TD [(Tol)-11.7(l-l)-7.7(ike)-505.6(rec)-13.5(ept)-9.3(or-2.)]TJ /F16 1 Tf 8.7913 0 TD [(Am)-505.7(J)-504.4(R)0(e)-9.8(spir)-511.8(Cr)-8.8(it)-509(Care)-508.1(Med)]TJ /F11 1 Tf 12.4575 0 TD [(\(2)-9.5(010\))-510.4(181\()-11.5(4\):36)-12.7(0)]TJ /F13 1 Tf 7.408 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(73)-9.6(.)]TJ -29.1632 -1.2699 TD [(doi:)-301.1(10.1164/rccm.200905-0696OC)]TJ -2.1544 -1.2624 TD [(192.)-499.3(Bons)-423.4(JA,)-413.3(Drent)-422.2(M,)-416.4(Bouwman)-420.1(FG,)-421.1(Mariman)-421.5(EC,)-416(van)-423.5(Dieijen-Visser)-416.7(MP,)]TJ 2.1544 -1.2699 TD 0.0155 Tc [(W)-6.8(o)1.5(dz)-6.9(ig)-524.3(WK)-6.4(.)-514.9(P)-4.6(o)-6.1(t)0(ent)-7.5(i)3.4(al)-520.7(b)-6.1(i)3.4(o)-6.1(m)-4(arke)-6.9(rs)-520(fo)-6.1(r)-520(d)-1.2(i)-4.2(a)-1.1(gnos)-6(is)-520(o)-6.1(f)-517.5(s)-6(a)-1.1(rc)-6.9(oi)-4.2(do)-6.1(si)-4.2(s)-520(u)-1.2(s)-6(i)3.4(ng)]TJ T* 0 Tc [(p)-9.1(rote)-13(omic)-15.2(s)-505.3(i)0(n)-514.3(ser)-12.5(um.)]TJ /F16 1 Tf 9.5321 0 TD [(Re)-9.8(spi)-14.1(r)-505.3(Med)]TJ /F11 1 Tf 5.246 0 TD [(\(2)-9.5(00)-9.6(7\))-508.4(10)-9.6(1\(8\))-11.4(:)-8.8(1687)]TJ /F13 1 Tf 7.9069 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(95)-9.6(.)-507.7(doi)-12.6(:)-507.7(10.)-10.8(1016)-11.6(/)]TJ -23.199 -1.2624 TD (j.rmed.2007.03.002)Tj -2.1544 -1.2699 TD [(193.)-499.3(Moore)-487.1(BJB,)-478.6(June)-491.4(CH.)-482.5(Cytokine)-482.6(release)-489.1(syndrome)-484.9(in)-484(severe)-483.8(COVID-19.)]TJ /F16 1 Tf 2.1544 -1.2624 TD (Science)Tj /F11 1 Tf 3.1068 0 TD [(\(2020\))-300.7(368\(6490\):473)]TJ /F13 1 Tf 8.6023 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(4.)-300.8(doi:)-301.1(10.1126/science.abb8925)]TJ -14.3699 -1.2699 TD [(194.)-499.3(Christenson)-225.6(K,)-219.6(Bjrkman)-219.3(L,)-226.1(Ahlin)-217.9(S,)-221.1(Olsson)-220.3(M,)-219.8(Sjholm)-219.1(K,)-227.2(Karlsson)-217.9(A,)-221.3(et)-219.3(al.)]TJ 2.1544 -1.2624 TD 0.0165 Tc [(Endogenous)-519(Acute)-520(P)4(hase)-512.4(S)-6.8(e)1.6(rum)-517(A)0.5(myloid)-514.2(A)-513.5(L)-4.3(acks)-519(Pro-In)]TJ /F12 1 Tf 25.565 0 TD 0 Tc ()Tj /F11 1 Tf 0.5443 0 TD 0.0148 Tc [(am)-4.7(mat)-8.2(ory)]TJ -26.1093 -1.2699 TD 0.0294 Tc [(Activity,)-523.6(C)-2.5(ontra)5.3(s)0.3(ting)-525.5(the)-529.7(T)0.9(wo)-528.9(Recombina)5.3(n)-4.1(t)-522.8(V)0.7(ariants)-528.8(T)0.9(hat)-522.8(A)-1.7(ctivate)]TJ T* 0 Tc [(Human)-452.5(Neutrophils)-457.3(through)-452.6(Dif)63(ferent)-451.7(Receptors.)]TJ /F16 1 Tf 20.9918 0 TD [(Front)-453.1(Immunol)]TJ /F11 1 Tf 6.7503 0 TD (\(2013\))Tj -27.7421 -1.2624 TD [(22\(4\):92.)-307.9(doi:)-301.1(10.3389/)]TJ /F12 1 Tf 9.0407 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (mmu.2013.00092)Tj -11.7242 -1.2699 TD [(195.)-499.3(Bjorkman)-400.7(L,)-392.4(Raynes)-390.2(JG,)-399.9(Shah)-391.4(C,)-395.9(Karlsson)-399.4(A,)-387.6(Dahlgren)-401.3(C,)-388.4(Bylund)-401.1(J.)-389.8(The)]TJ 2.1544 -1.2624 TD (proin)Tj /F12 1 Tf 2.1922 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-277.4(activity)-281.8(of)-274.8(recombinant)-277.9(serum)-275.5(amyloid)-278(A)-280.6(i)0(s)-275.5(not)-274.6(shared)-278.3(by)]TJ -2.7213 -1.2699 TD [(t)-7.9(h)-13.3(e)-513.8(e)0(n)-18.1(d)-9.1(og)-17.1(en)-18.1(o)-14(u)-9.1(s)-512.9(p)-9.1(r)-14(o)0(t)-14.4(e)0(i)-19.4(n)-517.3(in)-521.8(t)-7.9(h)-13.3(e)-513.8(c)-14.9(ir)-11(c)-14.9(u)-9.1(la)-16(t)-7.9(i)-12.1(on)-17.3(.)]TJ /F16 1 Tf 18.845 0 TD [(A)-9.2(r)0(t)-14.3(h)-11.6(ri)-16.1(t)-7.9(i)-9.7(s)-521.2(R)0(h)-15.7(e)-13.2(um)-10.8(a)-9.9(t)-7.9(o)-15.8(l)]TJ /F11 1 Tf 8.8593 0 TD [(\(2)-17.1(01)-17.1(0\))]TJ -27.7043 -1.2624 TD (62:1660)Tj /F13 1 Tf 3.0917 0 TD ()Tj /F11 1 Tf 0.514 0 TD [(5.)-300.8(doi:)-301.1(10.1002/art.27440)]TJ -5.7601 -1.2699 TD [(196.)-499.3(Yamada)-292.3(T,)-286.7(Okuda)-288.4(Y,)-283.3(Takasugi)-291.2(K,)-287.7(Itoh)-284.2(K,)-287.7(Igari)-287.2(J.)-291.5(Relative)-286.4(serum)-290.6(amyloid)-285.5(A)]TJ 2.1544 -1.2699 TD [(\(SAA\))-253.7(values:)-262.4(the)-255.3(in)]TJ /F12 1 Tf 8.0127 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(uence)-253.5(of)-252.2(SAA1)-256.6(genotypes)-258.1(and)-255.7(corticosteroid)-260.9(treatment)]TJ -8.5418 -1.2624 TD [(in)-370.7(Japanese)-379.5(patients)-373(with)-369.2(rheumatoid)-372.3(arthritis.)]TJ /F16 1 Tf 19.4724 0 TD [(Ann)-368.3(Rheum)-372.4(Dis)]TJ /F11 1 Tf 6.9469 0 TD [(\(2001\))-368.7(60)]TJ -26.4192 -1.2699 TD (\(2\):124)Tj /F13 1 Tf 2.8271 0 TD ()Tj /F11 1 Tf 0.5065 0 TD [(7.)-300.8(doi:)-301.1(10.1136/ard.60.2.124)]TJ -5.4879 -1.2624 TD [(197.)-499.3(Grif)]TJ /F12 1 Tf 3.7191 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ths)-367.7(K,)-370.8(Maxwell)-373.9(AP,)-369.9(McCarter)-370.4(RV,)-368.3(Nicol)-367.3(P,)-369(Hogg)-371.4(RE,)-367.3(Harbinson)-374.3(M,)]TJ -2.0939 -1.2699 TD [(et)-226.9(al.)-228.9(Serum)-224.4(amyloid)-225.1(A)-227.7(levels)-227.1(are)-226.8(associated)-224.6(with)-225.6(polymorphic)-228.4(variants)-231(in)-227(the)]TJ 0 -1.2624 TD 0.0221 Tc [(serum)-519(a)-2(myl)7.5(o)0.5(i)-5.2(d)-516.2(A)-523(1)-519.4(and)-523.7(2)-519.4(genes.)]TJ /F16 1 Tf 15.4433 0 TD 0.0217 Tc [(Ir)-521.4(J)-520.5(M)4.7(ed)-521.5(Sci)]TJ /F11 1 Tf 6.1607 0 TD 0.0194 Tc [(\(201)-8.1(9\))-522(188)-8.1(:1)-8.1(175)]TJ /F13 1 Tf 6.9922 0 TD 0 Tc ()Tj /F11 1 Tf 0.5367 0 TD 0.0199 Tc (83.)Tj -29.133 -1.2699 TD 0 Tc [(doi:)-301.1(10.1007/s11845-019-01996-8)]TJ -2.1544 -1.2699 TD [(198.)-499.3(Zhang)-342.7(J,)-344.4(Guo)-343.2(W,)-340.9(Shi)-343.5(C,)-343(Zhang)-342.7(Y,)-343.8(Zhang)-342.7(C,)-343(Zhang)-342.7(L,)-347.1(et)-340.3(al.)-342.3(Copy)-337.8(number)]TJ 2.1544 -1.2624 TD [(var)-10.9(iatio)-9.8(ns)-508.6(in)-506.7(serum)-509.8(amy)-8.9(loid)-511(A)-499.8(p)-9.1(lay)-502.9(a)-507.9(role)-511(in)-506.7(the)-504.7(det)-9.2(erm)-10.5(inat)-9.6(ion)-505.6(of)-509.2(its)]TJ 0 -1.2699 TD 0.0609 Tc [(individ)6.4(u)-1.2(al)-550.8(baseline)-551.1(concentrat)7.6(io)9.1(ns.)]TJ /F16 1 Tf 16.9703 0 TD 0.0563 Tc [(Cl)-7.1(in)-561.7(C)-6.6(h)-0.6(em)]TJ /F11 1 Tf 5.5635 0 TD 0.0581 Tc [(\()-7.1(2018\))-566.5(64:402)]TJ /F13 1 Tf 6.4858 0 TD 0 Tc ()Tj /F11 1 Tf 0.5745 0 TD 0.0577 Tc (4.)Tj -29.5941 -1.2624 TD 0 Tc [(doi:)-301.1(10.1373/clinchem.2017.279372)]TJ 7.4999 0 0 7.4999 306.1417 417.4298 Tm [(199.)-499.3(O)]TJ /F13 1 Tf 2.88 0 TD ()Tj /F11 1 Tf 0.2041 0 TD [(Br)24.8(ie)25.9(n)-313.2(K)15.9(D,)-300.2(B)16.1(r)0(e)24.1(h)0(m)-297.3(B)16.1(J,)-299.1(S)14.5(e)0(e)23.2(l)15.7(ey)-297.7(RJ)21.3(,)-303.6(B)0(e)23.9(a)0(n)-299.5(J)0(,)-299.1(W)15.5(e)15.4(n)0(e)19.7(r)-308.8(M)15.7(H)0(,)-299.5(D)18.4(an)25.5(ie)25.9(ls)-300.7(S)14.5(,)-311.1(e)15.4(t)-310.3(al)29.4(.)-311.1(D)0(i)21.4(e)15.4(t-)]TJ -0.9298 -1.2624 TD [(in)22.4(du)27.1(c)15.4(e)0(d)-160.1(w)0(e)19.6(i)18.1(gh)21.4(t)-166.7(l)0(o)24.3(s)0(s)-164(i)18.1(s)-172.7(a)0(s)22.4(s)16.3(oc)24(ia)24.2(te)30.1(d)-175.4(w)0(i)22.4(t)0(h)-157.2(d)0(e)28.9(c)0(r)24.1(e)15.4(as)22.4(e)15.4(s)-172.7(in)-166.6(pl)29.2(as)22.4(m)18.3(a)-175.3(s)16.3(e)0(r)24.1(u)0(m)-164.7(a)0(m)32(y)0(l)20.1(o)16.2(id)-157.3(A)-174.8(a)0(n)25.6(d)]TJ 0 -1.2699 TD [(C-)27.3(re)24.1(ac)21.5(ti)32.9(ve)-222.1(pr)29.8(ot)23.4(e)15.4(i)0(n)-219.5(i)0(n)22.4(d)0(e)28.9(p)0(e)21.4(n)19.4(de)21.4(nt)-215.3(of)-214.4(di)24.1(et)22.6(ar)30(y)-229.9(m)0(a)24.4(c)0(r)24.1(o)16.2(nu)25.4(tr)23.5(ie)25.9(nt)-215.3(co)24(mp)24.3(o)16.2(s)0(i)26.8(t)0(i)25.3(o)0(n)-221.4(i)18.1(n)-230(o)0(b)24.9(e)15.4(se)]TJ T* [(su)22.3(b)16.2(j)15.7(ec)23.2(ts)23.5(.)]TJ /F16 1 Tf 3.4772 0 TD 0.2234 Tc [(JC)223.4(l)248.3(i)223.4(n)11.5(E)223.4(n)248.1(d)239.6(o)223.4(c)242.5(r)239.7(i)223.4(n)245.8(o)237.8(lM)223.4(e)246.2(t)223.4(a)250.9(b)]TJ /F11 1 Tf 9.517 0 TD 0 Tc [(\()18(2)0(0)20.7(0)17.9(5\))-213.6(90)20.7(:2)31.8(24)20.7(4)]TJ /F13 1 Tf 5.7601 0 TD ()Tj /F11 1 Tf 0.4989 0 TD [(9.)-217.7(do)29.8(i:)-217.4(1)17.9(0)0(.)24.2(1)0(2)28.2(1)0(0)20.7(/)0(j)27.7(c)15.4(.2)24.2(00)28.2(4-)24.2(10)28.2(11)]TJ -21.4075 -1.2624 TD [(200.)-499.3(Ho)27.9(ri)19.3(uc)28.9(hi)-206.8(Y,)-207.7(Hi)22.2(r)16.3(a)0(y)25.7(a)0(m)24.4(a)-220.6(S)14.4(,)-220.4(S)14.4(o)0(d)22.2(a)-220.6(S)14.5(,)-220.4(S)14.5(e)0(i)25.9(n)0(o)-206.3(U)0(,)-209.5(K)15.9(on)-213.8(M)15.7(,)-220.4(Ue)26.3(no)-206.3(T,)-211.2(e)15.4(t)-219.6(al)29.4(.)-220.4(S)0(t)21.6(a)0(t)28.4(i)0(n)-211.9(t)0(h)31.7(e)0(r)24.1(a)0(p)27.2(y)]TJ 2.1544 -1.2699 TD [(re)16.5(duc)19.8(es)-429.5(in)]TJ /F12 1 Tf 4.1953 0 TD ()Tj /F11 1 Tf 0.5216 0 TD [(am)16.9(mat)24.1(ory)-424.1(ma)16.9(rke)21.7(rs)-428.6(in)-431.1(hyp)19.9(er)16.5(ch)17.2(ol)16.8(es)16.5(te)15(ro)17.4(le)15.9(mic)-424.5(pat)19.3(ie)18.4(nts)-425.8(wi)22.3(th)-429.4(hig)24.4(h)]TJ -4.7169 -1.2624 TD [(ba)22.3(s)16.3(e)15.4(li)26.2(ne)-214.7(le)23.5(ve)27.4(ls)24.4(.)]TJ /F16 1 Tf 5.8432 0 TD [(J)-224.7(A)0(t)20.7(h)18.7(er)25.8(os)22.4(cl)24.4(e)17(r)-233.2(T)18.5(h)0(r)19.8(o)14.5(m)17.5(b)]TJ /F11 1 Tf 8.3982 0 TD [(\(2)28.3(01)28.2(0\))-213.6(17)20.7(:7)24.2(2)17.9(2)]TJ /F13 1 Tf 5.299 0 TD ()Tj /F11 1 Tf 0.4989 0 TD [(9)17.9(.)-228(do)22.2(i)18.1(:)-228(10)28.2(.5)24.2(55)20.7(1)17.9(/)0(j)27.7(a)0(t)20.9(.)0(3)24.2(6)17.9(32)]TJ -22.1937 -1.2699 TD [(201.)-499.3(Giugliano)-382.2(D,)-383.4(Ceriello)-387.9(A,)-380(Esposito)-384.9(K.)-378.4(The)-389.2(ef)64.5(fects)-380.5(of)-388.2(diet)-376.7(on)-387.7(in)]TJ /F12 1 Tf 27.6514 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (ammation:)Tj -26.0262 -1.2624 TD [(emphasis)-309.9(on)-312.1(the)-308.2(metabolic)-309.8(syndrome.)]TJ /F16 1 Tf 15.6323 0 TD [(J)-300.3(A)0(m)-309.2(Coll)-311.2(Cardiol)]TJ /F11 1 Tf 7.5062 0 TD [(\(2006\))-308.2(48:677)]TJ /F13 1 Tf 5.5257 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (85.)Tj -29.1708 -1.2699 TD [(doi:)-301.1(10.1016/j.jacc.2006.03.052)]TJ -2.1544 -1.2699 TD [(202.)-499.3(Pruett)-459.4(BS,)-462(Pruett)-459.4(SB.)-462(An)-457.7(explanation)-460.6(for)-462.7(the)-459.4(paradoxical)-463.1(induction)-463.8(and)]TJ 2.1544 -1.2624 TD [(suppression)-324(of)-312.6(an)-314.6(acute)-320.4(phase)-317.2(response)-317.2(by)-311.9(ethanol.)]TJ /F16 1 Tf 21.0371 0 TD (Alcohol)Tj /F11 1 Tf 3.2731 0 TD [(\(2006\))-315.8(39:105)]TJ /F13 1 Tf 5.5257 0 TD ()Tj /F11 1 Tf -29.836 -1.2699 TD [(10.)-305.6(doi:)-301.1(10.1016/j.alcohol.2006.08.003)]TJ -2.1544 -1.2624 TD [(203.)-499.3(Al-Sieni)-377.2(AI,)-372.1(Al-Alawy)-372.6(AI,)-379.7(Al-Shehri)-372.1(ZS,)-376.4(Al-Abbasi)-375.5(FA.)-374.1(Serum)-375.6(amyloid-A)]TJ 2.1544 -1.2699 TD [(protein)-377.6(and)-369.1(serum)-373.8(rheumatoid)-372.3(factor)-373.5(as)-370.7(serological)-373.3(surrogate)-372(markers)-374.8(for)]TJ 0 -1.2624 TD [(smoking)-279.9(risk)-276.7(factor)-275.2(in)-272.4(Saudi)-281.9(population.)]TJ /F16 1 Tf 16.4487 0 TD [(Pak)-274.9(J)-277.6(Pharm)-274.7(Sci)]TJ /F11 1 Tf 6.7201 0 TD [(\(2013\))-278(26:239)]TJ /F13 1 Tf 5.4955 0 TD ()Tj /F11 1 Tf 0.5065 0 TD (43.)Tj /F14 1 Tf -31.3251 -2.6003 TD (Con)Tj /F24 1 Tf 1.7462 0 TD ()Tj /F14 1 Tf 0.5745 0 TD [(ict)-305.5(of)-299.4(Interest:)]TJ /F11 1 Tf 6.2665 0 TD [(The)-298.5(authors)-300.4(declare)-302.9(that)-302.7(the)-300.6(research)-297.7(was)-306(conducted)-301.3(in)-302.6(the)]TJ -8.5872 -1.2699 TD [(absence)-273.8(of)-267.3(any)-264.8(commercial)-275.7(or)]TJ /F12 1 Tf 12.2156 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(nancial)-270.1(relationships)-273.1(that)-272.4(could)-265.8(be)-270.8(construed)-275(as)-264.8(a)]TJ -12.7447 -1.2624 TD [(potential)-304.4(con)]TJ /F12 1 Tf 5.2914 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ict)-299.5(of)-305.1(interest.)]TJ /F16 1 Tf -5.8205 -2.5399 TD [(Co)19.6(py)24(ri)21.7(gh)18.9(t)-423.7()-424.2(2)14.4(0)0(2)21.4(1)-424(So)18.9(ri)21.7(c)]TJ /F20 1 Tf 9.5926 0.0454 TD ()Tj /F16 1 Tf 0.3024 -0.0454 TD [(Ho)20.2(sm)17.9(an)22.2(,)-421.1(K)0(o)16.9(s)-422.9(an)22.2(d)-422.2(L)17(am)15.2(o)14.4(t)0(.)-413.9(T)0(h)22(i)0(s)-409.9(i)0(s)-409.9(a)0(n)-416.2(o)14.5(pe)19.8(n-)17.4(ac)24.9(ces)29.6(s)-422.9(a)0(r)21.5(t)0(i)20.2(c)0(l)16.8(e)]TJ -9.8949 -1.2624 TD 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obj<> endobj 1963 0 obj<> endobj 1964 0 obj<>stream Acrobat Distiller 7.0 (Windows) serum amyloid A, biomarkers, markers of inflammation, rheumatic inflammatory disease, autoinflammatory disease, amyloidosis, biological therapy, COVID-19 2021-02-18T11:46:03+08:00 2021-02-18T13:49:13+08:00 Arbortext Advanced Print Publisher 10.0.1306/W Unicode 2021-02-18T13:49:13+08:00 application/pdf Iva Sori&cacute Hosman Ivanka Kos Lovro Lamot Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD) Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Biomarker serum amyloid A biomarkers markers of inflammation rheumatic inflammatory disease autoinflammatory disease amyloidosis biological therapy COVID-19 uuid:416a1a63-f95e-4e2c-b581-1aab3e75cdfd uuid:4897e102-e8e1-44c2-9214-f8ac846b4bd7 endstream endobj xref 1066 4 0001818104 00000 n 0001818179 00000 n 0001818318 00000 n 0001818462 00000 n 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