Background:Systemic sclerosis (scleroderma, SSc) is a rare complex connective tissue disease associated with high mortality and high morbidity1. Active SSc are typically treated with immunosuppressants, which may create a variety of severe side-effects, especially for long-term treatment2. As the pathogenesis of SSc is still a matter of debate, growing evidences have focused on the immune disorders3. However, the quantitative status of lymphocyte subsets in SSc patients are unclear and effects of immunomodulatory combination therapies (avoiding side-effects of conventional therapy) on the lymphocyte subsets are unknown.Objectives:To investigate the quantitative status of peripheral lymphocyte subpopulations and CD4+T subsets in SSc patients for the exploration of SSc pathogenesis and evaluate the effects of new immunomodulatory combination therapies on those cells.Methods:From July 2014 to December 2019, total 166 patients with SSc and 206 healthy controls (HCs) were enrolled in this study, in which, 79 follow-up patients received immunomodulatory drugs (IMiDs) such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and Tregs in peripheral blood of these subjects were detected by flow cytometry combined with standard absolute counting beads.Results:Patients with SSc had lower absolute counts of total T, NK, Th2, Th17 and Tregs as compared with those of HCs (P<0.05) (Figure 1). After immunomodulatory combination treatments, there were increases in a various of peripheral lymphocyte subsets such as T, B and CD8+T (P< 0.05). Moreover, the increased level of Tregs was much more dramatical than those of other lymphocyte subsets, resulting in the decrease ratios of Teffs/Tregs such as Th1/Tregs and Th2/Tregs and rebuilding immunologic equilibrium (Figure 2).Conclusion:This cross-sectional study clarified the abnormal status of lymphocyte subsets in SSc patients, suggesting lymphocyte subsets, especially Tregs, might be relevant and play a crucial role in the pathogenesis of SSc, thus providing a potential therapeutic target for SSc patients. Immunomodulatory combination therapies effectively increase the level of Tregs as well as other lymphocytes to some degree and maintain the immunologic equilibrium, which may help for SSc patients’ symptom remission.References:[1]Denton CP, Khanna D. Systemic sclerosis. Lancet 2017;390(10103):1685-99. doi: 10.1016/S0140-6736(17)30933-9 [published Online First: 2017/04/18][2]Winthrop KL, Weinblatt ME, Bathon J, et al. Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019. Ann Rheum Dis 2020;79(1):88-93. doi: 10.1136/annrheumdis-2019-216151 [published Online First: 2019/10/31][3]Skaug B, Khanna D, Swindell WR, et al. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Ann Rheum Dis 2019 doi: 10.1136/annrheumdis-2019-215894 [published Online First: 2019/11/27]Acknowledgments :None.Disclosure of Interests:None declared
Role of lectin pathway complement proteins and genetic variants in organ damage and disease severity of systemic sclerosis: a cross-sectional study
