P038 Recent thymic emigrant t cells increase in rheumatoid patients treated with abatacept. (21st February 2018)

• Record Type: Journal Article
• Authors: Piantoni, S; Regola, F; Tincani, A; Airò, P
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 1
• Page Start: A29
• Page End: A29
• Publication Date: 2018-02-21
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2018.60
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Introduction: CD4 +T cells in rheumatoid arthritis (RA) display a peculiar restriction of the T-cell receptor (TCR) repertoire which compromises their ability to react to novel antigens. 1 We demonstrated that this process could be partially reverted by abatacept (ABA), which is a blocker of T lymphocyte co-stimulation, used in the treatment of RA. 2 To better understand the mechanisms underlying this phenomenon, we speculated that ABA could influence the frequency of peripheral T cell subpopulations, even at early stages of maturation. The homeostasis of the naïve T cell pool is maintained not only by thymus production, but also by mechanisms of peripheral replication involving TCR activation revealed by CD31 down-modulation. Indeed, CD4+CD45RA+CD31+T cells have been described as recent thymic emigrants ( RTE ) newly produced by the thymus and CD4+CD45RA+CD31 T cells as central naïve, involved in a self-renewal peripheral process. Objectives: We aimed at profiling circulating naïve CD4+CD45RA+T cells, by assessing their expression of CD31 (PECAM-1). 3 Methods: Thirty-one RA patients (median age [10°−90° percentile] 42 [25–64] years) were evaluated before and after 6 month of ABA therapy. Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry. Wilcoxon-signed rank test and Spearman rank correlation were used for the comparisons. Results: After ABA therapy, the absolute number of total T CD4 +increased from 780 [423–1351] to 1000 [658–1566] cells/mm 3 (p=0.01). Total naïve CD4 +increased in percentage (33 [18–56] vs 40 [20–61]% of CD4+; p=0.02) and in absolute number (257 [82–568] vs 344 [62–689] cells/mm 3 ; p=0.03). In parallel, the number of RTE increased in percentage (10.6 [2–26] vs 11.6 [3–25]% of CD4+; p=0.04) and in absolute number (51 [15–194] vs 110 [23–271] cells/mm 3 ; p=0.01). The central naïve counterpart did not show significant variations in percentage (29 [23–40] vs 27 [20–38]% of CD4+; p=0.20) nor in absolute number (191 [41–404] vs 242 [76–526] cells/mm 3 ; p=0.20). No correlation was found between age and RTE number at baseline. Conclusions: The number of total naïve T cells increases after therapy with ABA together with the number of RTE, suggesting a thymic output boost. Besides the peripheral effect in reducing the number of effector T cells which was showed by previous studies, 4 ABA could have a role in promoting the immune reconstitution at the early stage of T cell development. References: . Wagner UG, et al. PNAS 1998. . Imberti L, et al. J Transl Med2015. . Kohler S, et al. Blood2009. . Airò P, et al. Trends Mol Med2013. Disclosure of interest: None declared