B CELLS FROM PATIENTS WITH RHEUMATOID ARTHRITIS SHOW CONSERVED CD39-MEDIATED REGULATORY FUNCTION AND INCREASED CD39 EXPRESSION AFTER POSITIVE RESPONSE TO THERAPY

FERRERO, PAOLA VIRGINIA; BOSSIO, S.N.; CADILE, ISAAC I.; GRUPPI, ADRIANA; AMEZCUA VESELY, M.C.; ACOSTA, CRISTINA D. V.; MUSSANO, EDUARDO; ACOSTA RODRÍGUEZ, EVA V.; ZACCA, ESTEFANÍA RAQUEL; PONCE, N.E.; ONETTI, LAURA; MONTES, CAROLINA

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2020

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. Under inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cell constitutively express both ectonucleotidases, turning these cells potentially suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expressions on B cells from untreated or treated RA patients, in comparison to healthy controls (HC), showed significant changes. We observed that CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression and suppressed CD4+ and CD8+ T cell proliferation and intracellular cytokine production. CD39-inhibitor significantly restored proliferation and cytokine-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 expression on B cells after treatment, while most of the non-responders (NR) patients exhibited a reduction in the ectoenzyme expression. Consistent with their increased expression of CD39, after treatment, B cells from R-RA patients showed higher capacity to hydrolyze eATP and lower levels of anti-cyclic citrullinated peptide and Rheumatoid factor. Our results point the modulation of ectoenzymes/ADO pathway as potential therapy target for improvement the course of RA.