Changes in peripheral blood B cell subsetsin patients with rheumatoid arthritis

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica, LXIV Reunión Anual de la Sociedad Argentina de Inmunología, XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2016

SAI, SAFE Y SAIC

Rheumatoid arthritis (RA) is the most frequent autoimmune disease that primarily affects joints, and, sometimes, is associated with extra-articular manifestations. Despite major progress in RA treatment, response to therapy is often suboptimal. Then, predictive biomarkers of response to treatment are needed. It has been reported that the absence and dysfunction of some B cell subsets is associated with autoimmunity. The aim of this study was to evaluate B cell subsets in RA patients and healthy individuals and analyze the effect of treatment in these populations.Peripheral blood samples were obtained from healthy controls (HC, n=14), untreated RA patients (uRA, n=15), RA patients treated with Metotrexate (RA-Mtx, n=18), TNF inhibitors (RA-anti-TNF, n=13) or a JAK inhibitor Tofacitinib (RA-Tofa, n=5). Samples were obtained at baseline and after 3 months of treatment (n=13). Disease activity was evaluated by 28-joint count Disease Activity Score (DAS-28) and the treatment response by the EULAR response criteria. By flow cytometry we observed that % of immature B cells CD19+CD24hiCD38hi in uRA and RA-Mtx were similar to HC, however a significantly diminished % was observed in RA- anti-TNF and RA-Tofa (p<0,05). The values of mature B cells CD19+CD24intCD38int, memory B cells CD19+CD24hiCD38- and CD19+CD24-CD38hi B cells were similar between groups. Notably, a significant increase in the CD19+CD24hiCD38- subset (p<0,05) and a significant decreased in the CD19+CD24hiCD38hi subset (p<0,05), was observed in good responders RA-treated patients. Both subsets present equal % of the inhibitory molecule PDL1- and LAP-expressing cells, and the CD19+CD24hiCD38- had higher % of CD39+CD73+ cells. These results suggests that changes in B cell subsets could be used as predictive biomarkers of response to therapy. Furthermore, TNF and the JAK-STAT pathway could be involved in the development/survival of CD19+CD24hiCD38hi, because when these pathways are inhibited that population decreases.