Tofacitinib treatment of Rheumatoid Arthritis: Increases senescent T‐cell frequency in patients and limits T‐cell function in vitro

ALAMINO, VANINA A.; ONOFRIO, LUISINA I.; ACOSTA, CRISTINA DEL VALLE; FERRERO, PAOLA V.; ZACCA, ESTEFANÍA R.; CADILE, ISAAC I.; MUSSANO, EDUARDO D.; ONETTI, LAURA B.; MONTES, CAROLINA L.; GRUPPI, ADRIANA; ACOSTA RODRIGUEZ, EVA V.

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Año: 2023

0014-2980

nraveling the immune signatures in rheumatoid arthritis (RA) patients receiving various treatment regimens can aid in comprehending the immune mechanisms’ role in treatment efficacy and side effects. Given the critical role of cellular immunity in RA pathogenesis, we sought to identify T-cell profiles characterizing RA patients under specific treatments.We compared 75 immunophenotypic and biochemical variables in healthy donors (HD) and RA patients, including those receiving different treatments as well as treatment-free patients. Additionally, we conducted in vitro experiments to evaluate the direct effect of tofacitinib on purified naïve and memory CD4+ and CD8+ T cells.Multivariate analysis revealed that tofacitinib-treated patients segregated from HD at the expense of T-cell activation, differentiation, and effector function-related variables. Additionally, tofacitinib led to an accumulation of peripheral senescent memory CD4+ and CD8+ T cells. In vitro, tofacitinib impaired the a