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Abstract: We analyzed peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 16 rheumatoid arthritis (RA), 9 spondyloarthritis (SpA), 3 microcrystal arthritis patients, to define the presence of Th17 and Th1 and their relationship with inflammatory activity, and TCR-zeta chain and ZAP-70 levels. Th17 were significantly higher in SF than in PB and more abundant in microcrystal arthritis patients compared to the other groups. Irrespectively of the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (C reactive protein [CRP], fibrinogen, erythrocyte sedimentation rate) inflammation markers. SF Th1 percentages directly correlated with inflammation and disease activity (CRP, swollen joint count [SJC]) indices in SpA, but not in RA patients. These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. The TCR-zetadim lymphocytes in SF were found to produce the highest amounts of cytokines including IL-17, whereas no ZAP-70 impairment was associated to Th17. [ABSTRACT FROM AUTHOR]

Abstract: B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFα blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity. [Copyright &y& Elsevier]