PD-L1 regulatory B cells are significant decreased in Rheumatoid Arthritis and increase in good responders treated patients.

ZACCA E; ONOFRIO L; ACOSTA C; FERRERO P; ALONSO SM; RAMELLO MC; MONTES CL; MUSSANO E; ONETTI L; CADILE I; TABOADA C; RETA L; ACOSTA RODRIGUEZ EV; GRUPPI A

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Rheumatoid arthritis (RA) is the most frequent autoimmune disease.Immune tolerance and prevention of autoimmunity can beexerted by different subsets of regulatory B cells (Bregs). PD-L1functions as a regulatory protein to maintain T cell self-tolerance,and could play a role in determining Breg activity in RA. We aimedhealthy individuals and analyze whether PD-L1 expression on Bcells 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 treatedwith Metotrexate (MTX, n=20), with TNF inhibitors (anti-TNF, n=19)or with JAK inhibitor Tofacitinib (TOFA, n=6). In some patients, sampleswere 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. Weobserved 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-L1strongly 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 proliferationand cytokine secretion in a PD-L1 dependent manner. Interestingly,the % of CD19+CD24hiCD38-PDL1+ significantly increasedin good responders RA patients (p<0.01). Our findings suggest aregulatory role for the CD19+CD24hiCD38- that could be used aspredictive biomarker of response to therapy. Furthermore, PDL1induction on CD19+ B cells from RA patients, could provide newsperspectives for future Tx strategies.