LAUSR

Background: Rheumatoid arthritis (RA) is an aggressive immune-mediated joint disease with synovial inflammation and joint destruction characterized by abnormal immune responses to self-antigens1. An imbalance in pro- and anti-inflammatory lymphocyte subsets has been considered to contribute to the pathogenesis of RA2. However, the detailed lymphocyte statuses of RA patients are required clarified and the effect of immunomodulatory therapy on the lymphocyte subsets is unclear3. Objectives: To investigate the status of lymphocyte subsets in peripheral blood (PB) of RA patients at relatively large-sample size and the changes of them after our immune regulatory combination treatment. Methods: This cross-sectional study enrolled 3016 patients with RA who met the ACR’s revised RA diagnostic classification in 1987 as well as 206 healthy controls (HCs). Among these participations, 1415 patients have received the treatment of immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid etc. Flow cytometry (FCM) was used to measure the levels of PB lymphocyte subgroups and CD4+T subsets in RA patients before and after the treatments and HCs. Data were expressed as mean ± standard deviation to the distribution. Independent-samples T test and paired-samples T test were applied. P value <0.05 were considered statistically significant. Results: Compared with HCs, patients with RA had a lower absolute numbers of total T, CD8+T, NK and Tregs (P<0.05), decreased percentages of NK, Th1, Th2 and Th17 (P<0.05), but higher ratios of Teffs/Tregs such as Th1/Tregs and Th17/Tregs (P<0.05), indicating a disturbance of immune systems (Figure 1). After receiving combined immunomodulatory therapy, the absolute numbers of T, B, CD4+T, CD8+T, NK, Th1, Th17 and Tregs were dramatically increased (P<0.05) and the percentages of B, Th1, CD4+T and Tregs were also increased (P<0.05). Although these subsets increased globally, the ratio of Teffs/Tregs such as Th2/Tregs and Th17/Tregs tended to decrease, suggesting a rebalance of immune systems(Figure 2). Conclusion: Impaired peripheral lymphocytes especially insufficiency of Tregs might played an important role in pathogenesis of RA. Immunoregulatory combination therapies could promote the proliferation and functional recovery of Tregs in patients and help to alleviate disease activity. References: [1]Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. (1474-547X (Electronic)) [2]Kondo Y, Yokosawa M, Kaneko S, et al. Review: Transcriptional Regulation of CD4+ T Cell Differentiation in Experimentally Induced Arthritis and Rheumatoid Arthritis. (2326-5205 (Electronic)) [3]Fonseka CY, Rao DA, Raychaudhuri S. Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis. (1879-0372 (Electronic)) Acknowledgments: None. Disclosure of Interests: None declared