Correlation between T cell exhaustion and progression, activity and response to treatment in patients with rheumatoid arthritis

Mar del Plata

Encuentro; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI), XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

SAI, SAIC y SAFE

Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease with articular and systemic effects. RA pathophysiology involves B and T cells (Tc) and detrimental interactions of proinflammatory cytokines. Treatment (Tx) includes antirheumatic drugs and biologic and synthetic agents. T cell exhaustion (Tex), a dysfunctional state characterized by loss of effector functions and expression of inhibitory receptors (IRs), is harmful during infections and cancer. As its role remains unexplored in autoimmunity, we aimed to study Tex during RA and its relationship to disease progression and activity and response to Tx. Fourteen healthy donors (HD) and 35 RA patients (RApt) (15 untreated and 20 with different Tx) were recruited in the Rheumatology Service (Hospital Nacional de Clínicas) and evaluated at different times post-Tx. Phenotype and function of different immune subpopulations from peripheral blood were evaluated by flow cytometry. Although the expression of the IRs CD160 and BTLA was barely modified by different Tx, there was a significant negative correlation (p<0.05) between the expression of CD160 on CD4 and CD8 Tc and the disease activity score (DAS28). Also, the % of CD8 Tc coexpressing the IRs BTLA, CD160, PD1 and TIM3 showed a negative correlation with DAS28 (p <0.02). Moreover, the increase in CD160 expression between months 0 and 3 post-Tx correlated to the response to Tx according to the EULAR criteria: being high, low and negative in RApt with good, moderate/low and poor responses, respectively. In vitro studies showed that the effector function of activated Tc from HD can be inhibited by CD160 and BTLA triggering. Whether the inhibitory pathway HVEM-CD160/BTLA is operative in RApt remains to be assessed. Altogether, our findings suggest that Tex correlates with RA disease activity and response to Tx and could be used as biomarker. Accordingly, IR triggering could emerge as a new RA Tx to inhibit exacerbated Tc effector function.