AB0499 ABNORMALITY OF PERIPHERAL LYMPHOCYTE SUBSETS IN BECHET’S DISEASE AND EFFECTS OF NEW IMMUNOREGULATORY COMBINATION THERAPIES ON THESE CELLS
Authors: Q. Y. Su, S. X. Zhang, L. M. Hao, J. Y. Yang, J. Bai, S. J. Guo, J. Luo, G. Y. Liu, C. Gao, X. LI
Journal: Annals of the Rheumatic Diseases (2020)

Background: Bechet’s disease (BD) is a chronic multisystemic vasculitis. Although its exact etiopathology is unknown, both autoimmune imbalances associated with genetic and abnormal immune response of effector lymphocytes promoted by infectious factors are suggested 1 . The increase of effector T cells (Teffs) and the decrease of regulatory T cells (Tregs) are possibly the involving factors in the pathogenesis of BD 2 . Importantly, we have developed new immunoregulatory combination therapies trying to restore the reduction of Tregs in rheumatic patients. Objectives: To examine abnormal levels of lymphocyte subsets in BD patients at a relatively large-sample size and to investigate whether the immunoregulatory combination therapies have therapeutic efficacy in BD. Methods: Total 384 BD patients and 206 healthy controls (HCs) were enrolled in this cross-sectional study. Proportions and absolute numbers of peripheral T, B, NK, CD4 + T, CD8 + T, Th1, Th2, Th17 and Treg subsets were analyzed by flow cytometry (FCM) for all participants. Among these patients,183 cases of BD patients were treated with immunoregulatory combination drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The levels of peripheral lymphocyte subsets were measured before and after the treatment. Compared-T test was used to compare continuous measures and to assess effect of these drugs. Results: Compared to HCs, the absolute numbers of various Teffs such as T, B, CD4 + T, CD8 + T, Th1 and Th17 cells were significantly increased in BD group ( P &lt;0.01), while the level of Tregs in patients with BD was severely decreased ( P &lt; 0.05), resulting in increased ratios (imbalance) of Th1/Tregs, Th2/Tregs and Th17/Tregs ( P &lt; 0.05) (Figure 1). After the IMiDs treatment, the levels of NK, CD4 + T, CD8 + T, Th1, Th17 cells as well as Tregs were significantly increased ( P &lt;0.05). But the increased Tregs was much more dramatical than those of Teffs, resulting in a decrease in ratios of Teffs/Tregs such as Th2/Tregs ( P &lt; 0.001) (Figure 2). Conclusion: Impaired balance of pro- and anti-inflammatory immune cells, especially insufficiency of Tregs, might be a cornerstone of the pathogenesis of BD. Immunoregulatory combination therapies could promote the proliferation and functional recovery of Tregs in patients with BD and might help to alleviate disease activity. References: [1]Yazici H, Seyahi E, Hatemi G, et al. Behcet syndrome: a contemporary view. Nat Rev Rheumatol 2018;14(2):107-19. doi: 10.1038/nrrheum.2017.208 [published Online First: 2018/01/04] [2]Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis 2019;78(2):209-17. doi: 10.1136/annrheumdis-2018-214229 [published Online First: 2018/11/26] Acknowledgments: None Disclosure of Interests: None declared