PD-L1 regulatory B cells are significant decreased in rheumathoid arthritis and increase in good responders treated patients

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAI, SAFE, SAH, SAP, SAB, SAFIS, SAA, SAB Y SAIC

Rheumatoid arthritis (RA) is the most frequent autoimmune disease. Immune tolerance and prevention of autoimmunity can be exerted by different subsets of regulatory B cells (Bregs). PD-L1 functions as a regulatory protein to maintain T cell self-tolerance, and could play a role in determining Breg activity in RA. We aimed to evaluate PD-L1 expression on B cell subsets in RA patients and healthy individuals and analyze whether PD-L1 expression on B cells had an influence on T cell activity and response to therapy. Peripheral blood samples were obtained from healthy controls (HC, n=25), untreated RA patients (untreated, n=24), RA patients treated with Metotrexate (MTX, n=20), with TNF inhibitors (anti-TNF, n=19) or with JAK inhibitor Tofacitinib (TOFA, n=6). In some patients, samples were obtained at baseline and after 3 months of Tx (n=18). RA activity was evaluated by 28-joint count Disease Activity Score (DAS-28) and the Tx response by the EULAR response criteria. We observed that among B cell subsets, the % of CD19+CD24hiCD38- correlated negative with DAS-28 (r= -0.4, p=0.0315) and that the % of CD19+CD24hiCD38-PDL1+ was not modified by different Tx, but a significant decrease in the % of CD19+CD24hiCD38-PDL1+ and CD19 PDL1+ B cells was observed in untreated RA patients (p<0.01). Moreover, we observed that the expression of PD-L1 strongly increased in HC (p<0.01) and untreated RA patients (p<0.01) when purified CD19+ B cells were cultured with CpG+IL-2. These PD-L1+ expressing B cells, suppressed CD8+ T cell proliferation and cytokine secretion in a PD-L1 dependent manner. Interestingly, the % of CD19+CD24hiCD38-PDL1+ significantly increased in good responders RA patients (p<0.01). Our findings suggest a regulatory role for the CD19+CD24hiCD38- that could be used as predictive biomarker of response to therapy. Furthermore, PDL1 induction on CD19+ B cells from RA patients, could provide news perspectives for future Tx strategies.