Background Abatacept (ABA) is a fusion molecule used in the treatment of Rheumatoid Arthritis (RA), which is able to compete with the engagement of CD28, the receptor for most important costimulatory signal for T cells. CD28-mediated signaling regulate several T-cell functions, including inflammatory cytokine production and Treg differentiation.
Objectives The aim of our study was to evaluate the effect of therapy with ABA on peripheral blood T lymphocyte cytokine production and on the number of circulating Treg.
Methods In 24 RA patients treated with ABA for at least 6 months the proportion and absolute number of peripheral blood T cells producing γ-interferon (γ-IFN) and interleukin-17 (IL-17) after in vitro stimulation, as well as those of Treg were longitudinally evaluated by flow-cytometry at baseline and after 6 and 12 months. The EULAR response criteria were applied to evaluate the clinical response to treatment. Sixteen healthy donors (HD) of comparable age were used as controls.
Results At baseline, compared with HD, RA patients had a higher percentage of circulating Treg (median percentage of CD4+ T cells 6.4 (25th-75th percentile: 4.8-7.5) vs 4.7 (4.0-4.8); p: 0.041), as well as of CD4+ and CD8+ T-cells producing IL-17 (1.1% of CD4+ T cells (0.4-2.0) vs 0.5 (0.3-0.8); p: 0.021; 1.2% of CD8+ T cells (0.7-1.8) vs 0.7 (0.5-0.8); p:0.006). After 6 months of therapy with ABA, there was a decrease of the percentage of Treg (from 6.4% of CD4+ T cells (4.8-7.5) to 4.8 (3.0-6.3); p: 0.008), of γ-IFN- and IL-17- producing CD8+ T cells (from 25.6% (12.9-34.4) to 17.2 (11.9-28.7), p:0.033; and from 1.2% (0.7-1.8) to 1.0 (0.6-1.3), p:0.035, respectively), while that of IL-17-producing CD4+ T cells decreased at 12 months (from 1.1% of CD4+ T cells (0.4-2.0) to 0.3 (0.2-0.5); p:0.005). The number of Treg and of IL-17 producing T-cells that were higher than in HD at baseline normalized after ABA therapy. All these variations were statistically significant only in RA patients with good clinical response (n:17), whereas the variations were milder and not significant in the other group of patients (n:7). The reduction of IL-17 producing CD4+T cells absolute number was correlated with the reduction of disease activity, evaluated with the DAS28-CRP (r: 0.477; p: 0.039).
Conclusions These findings enhance our understanding of the mechanism of action of ABA underlying the relevance of the CD28-mediated signaling as pharmacological target for RA.
Acknowledgements We acknowledge Bristol-Myers-Squibb Italia for the support to our study
Disclosure of Interest None Declared