Tofacitinib treatment of rheumatoid arthritis increases senescent T cell frequency in patients and limits T cell function in vitro.

Unraveling 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 activation, proliferation, and effector molecules expression and triggered senescence pathways in T-cell subsets upon TCR-engagement, with the most significant impact on memory CD8+ T cells. Our findings suggest that tofacitinib may activate immunosenescence pathways while simultaneously inhibiting effector functions in T cells, both effects likely contributing to the high clinical success and reported side effects of this JAK inhibitor in RA.

Dynamics of circulating follicular helper T cell subsets and follicular regulatory T cells in rheumatoid arthritis patients according to HLA-DRB1 locus.

B cells, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are part of a circuit that may play a role in the development or progression of rheumatoid arthritis (RA). With the aim of providing further insight into this topic, here we evaluated the frequency of different subsets of Tfh and Tfr in untreated and long-term treated RA patients from a cohort of Argentina, and their potential association with particular human leukocyte antigen (HLA) class-II variants and disease activity. We observed that the frequency of total Tfh cells as well as of particular Tfh subsets and Tfr cells were increased in seropositive untreated RA patients. Interestingly, when analyzing paired samples, the frequency of Tfh cells was reduced in synovial fluid compared to peripheral blood, while Tfr cells levels were similar in both biological fluids. After treatment, a decrease in the CCR7loPD1hi Tfh subset and an increase in the frequency of Tfr cells was observed in blood. In comparison to healthy donors, seropositive patients with moderate and high disease activity exhibited higher frequency of Tfh cells while seropositive patients with low disease activity presented higher Tfr cell frequency. Finally, we observed that HLA-DRB1*09 presence correlated with higher frequency of Tfh and Tfr cells, while HLA-DRB1*04 was associated with increased Tfr cell frequency. Together, our results increase our knowledge about the dynamics of Tfh and Tfr cell subsets in RA, showing that this is altered after treatment.

[Use of intravenous humana immunoglobulin in rheumatic diseases]. / Uso de inmunogtlobulina G humana endovenosa(IGEV) en enfermedades reumáticas.

INTRODUCTION: Preparations of intravenous immunoglobulin (IVIG) are used as treatment in different diseases such primary and secondary immunodeficiencies, autoimmune diseases, systemic inflammatory diseases, infectious diseases and allergic diseases among others. OBJECTIVE: to present 13 of our cases with the use of IVIG in different rheumatic diseases. PATIENTS AND METHODS: we retrospectively studied 13 patients (10 women and 3 men), mean age 29 years with different rheumatic diseases, that underwent conventional treatments without positive response. They received IVIG pulses, trying to improve or induce remission of their previous clinical situation. 6/13 patients met criteria for systemic lupus erythematosus (SLE), 2/13 had primary antiphospholipid syndrome (APL)one had polydermatomyositis (PDM), 1 juvenile arthritis, 1 panarteritis nodosa (cutaneous PAN), one Evans syndrome, and one with autoimmune uveitis. RESULTS: 7 of them had a positive response to therapy with IGEV evaluated by clinical and biochemical parameters. They remained with conventional treatments. One patient received a new IG EV pulse after 24 months, because of panniculitis reactivation. Clinical and biochemical response was poor in 4 of them, and 2 patients died. CONCLUSION: IVIg may be usefull in autoimmune rheumatic diseases when conventional therapies have failed. The therapeutic success is also limited. Only the 55 percent of our patients had a positive clinical response.