engleski

CD32+ B Lymphocytes and IL21R+ T Lymphocytes Are Associated with Disease Activity and Increased Levels of Proinflammatory Cytokines in Patients with Rheumatoid and Psoriatic Arthritis

Background Autoimmunity is presumed to be a major driving force in the pathogenesis of chronic rheumatic diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PSA). Although these forms of arthritis differ in their clinical features, both are marked by persistent inflammation and osteoresorption underpinned by aberrant lymphocyte populations and disturbed cytokine network. Objectives Various subpopulations of both T and B lymphocytes have been implied in RA and PSA, but their relevance to disease onset and progression remains largely unclear. The aim of our study was to define the association of T, B and NK cell subpopulations with cytokine levels and clinical parameters in RA and PSA patients. Methods Mononuclear cells were isolated from peripheral blood of healthy controls (n=35), RA (n=36) and PSA (n=13) patients, after obtaining Ethical approval and informed consent. Flow cytometry was applied to discriminate between T lymphocyte subpopulations: Th1/2 (CD3+CD4+CCR6-), Th17 (CD3+CD4+CCR4+CCR6+), Tfh (CD3+CD4+CXCR5+), Tc (CD3+CD8+) and memory Tc (CD3+CD8+CCR4+) ; B lymphocyte subpopulations: naïve (CD19+IgD+CD27-), unswitched memory (CD19+IgD+CD27+), class-switched memory (CD19+IgD-CD27-) and plasmablasts (CD19+IgD+CD27hiCD38+) ; and NK cells (CD3- CD19-CD56+). Markers of lymphocyte maturation (CD32), activation (CD86, IL21R, CD25) and migration (CD11b) were also analyzed. Frequencies of lymphocyte subpopulations were correlated with clinical parameters, including DAS28 (for RA and PSA) and BASDAI (for PSA with spondylitis). Finally, serum levels of various cytokines (TNF, IL4, IL6, IL10, IL17, CCL2, CCL3, CCL4, CCL5) were measured by flow cytometry bead based assay. Results Several subpopulations were found to be significantly expanded: CD32+ naïve (Ctrl 1.8%, RA 5.8%, PSA 6.0%) and memory B lymphocytes, both class- switched (Ctrl 1.8%, RA 5.3%, PSA 3.8%) and unswitched (Ctrl 4.0%, RA 16.8%, PSA 13.7%) ; memory Tc lymphocytes (Ctrl 4.8%, RA 6.8%, PSA 9.1%) ; and CD11b+ B lymphocytes (Ctrl 15.1%, RA 20.9%, PSA 20.2%). Significant correlations between lymphocyte subpopulations and clinical parameters included: positive association of IL21R+ T lymphocytes with DAS28 in RA (ρ=0.45) and negative with BASDAI in PSA (ρ=-0.86) ; negative association of class-switched memory B lymphocytes with DAS28 in RA (ρ=-0.52), but positive with BASDAI in PSA (ρ=0.71). Correlation of lymphocyte subpopulations with cytokine levels showed: significant positive association of CD32+ naïve B lymphocytes with TNF and CCL5 (ρ=0.55 and 0.54) ; CD32+ class- switched and unswitched memory B cells with TNF (ρ=0.47 and 0.55) and CCL4 (ρ=0.47 and 0.54) ; CD11b+ B lymphocytes with CCL4 (ρ=0.47) ; and IL21R+ T lymphocytes with TNF, CCL3 and CCL4 (ρ=0.42, 0.47 and 0.49). Conclusions Our results indicate novel T and B lymphocyte subpopulations induced in both RA and PSA. CD32+ B lymphocytes, as well as IL21R+ T lymphocytes, may be of particular interest as possible therapeutic targets, since their frequency is associated with disease activity and increased levels of proinflammatory and proresorptive cytokines. Acknowledgement The work has been fully supported by Croatian Science Foundation (project no. 5699).

osteoclast progenitors ; chemokines ; rheumatoid arthritis

nije evidentirano