engleski

Effect of chloroquine add-on therapy on TLR9 expression in systemic lupus erythematosus

Antimalarial agents (chloroquine and others) are used in treatment of systemic lupus erythematosus (SLE), although their precise mode of action is unclear. Recently, studies on murine SLE models demonstrated that endogenous DNA-containing immune complexes can induce autoantibody production via TLR9. This provided a possible explanation for chloroquine’ s efficacy in SLE treatment, as chloroquine blocks endosomal acidification and prevents TLR9 signaling. Therefore, we investigated the possible influence of chloroquine administration on TLR9 expression in 11 newly-discovered patients with SLE using flow cytometry. Patients were analyzed before therapy, after initial glucocorticoid treatment, and again after 3 months, when chloroquine was added and glucocorticoid dose reduced. The TLR9 expression in B cells was higher in patients on glucocorticoids than healthy controls (n=11), and decreased upon introduction of chloroquine. The ability of dexamethasone and chloroquine to modulate TLR9 expression and B cell activation by CpG, a synthetic TLR9 ligand, was also assessed in peripheral blood lymphocyte culture. Disease activity measured by SLEDAI score did not correlate either with TLR9 expression in whole blood cells or with autoantibody levels in patients’ sera. Serum levels of B-cell activating factor (BAFF), a factor necessary for both normal and autoreactive B-cell survival, decreased when patients were on glucocorticoids only, whereas glucocorticoids in in vitro conditions upregulated BAFF-R expression on B cells. The study suggests that observed differences in TLR9 expression, (and perhaps BAFF levels), in patients during treatment are likely to result from the therapy itself, and cautions careful interpretation of experimental results obtained from patients under treatment.

Toll-like receptors; TLR9; systemic lupus erythematosus; antimalarials; chloroquine; B cells; BAFF; glucocorticoids; autoimmunity

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