B cells from patients with Rheumatoid Arthritis show conserved CD39-mediated regulatory function and increased CD39 expression after positive response to therapy.

AMEZCUA VESELY, M.C.; ZACCA, E.R.; FERRERO, P.V.; ACOSTA, C.D.V.; PONCE, N.E.; BOSSIO, S.N.; MUSSANO, E.; ONETTI, L.; CADILE, I.; ACOSTA RODRÍGUEZ, E.V.; MONTES, C.L.; GRUPPI, A.

Congreso; Reunión Anual de Sociedades de Biociencias. SAIC - SAI - SAFIS; 2020

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressivejoint destruction associated with increased pro-inflammatory mediators. In inflammatorymicroenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exertsimmunosuppressive effects, by the consecutive action of the ectonucleotidases CD39and CD73. Mature B cells constitutively express both ectonucleotidases, converting thesecells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cellsfrom treated or untreated patients with RA. Neither the frequency of CD73+CD39+ andCD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells fromuntreated or treated RA patients showed significant changes in comparison to healthycontrols (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increasedtheir CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation andintracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNFproducing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RApatients, indicating that B cells from untreated RA patients conserved CD39-mediatedregulatory function. Good responder patients to therapy (R-RA) exhibited an increasedCD39 but not CD73 expression on B cells after treatment, while most of the nonresponder (NR) patients showed a reduction in ectoenzyme expression. The positivechanges of CD39 expression on B cells exhibited a negative correlation with diseaseactivity and rheumatoid factor levels. Our results suggest modulating ectoenzymes/ADOpathway as a potential therapy target for improving the course of RA