THU0332 ABSOLUTE REDUCTION OF REGULATORY T CELLS AND EFFICACY OF SHORT-TERM AND LOW-DOSE IL-2 IN PATIENTS WITH DERMATOMYOSITIS OR POLYMYOSITIS
Authors: Min Feng, Xiang-Cong Zhao, Chong Gao, Jing Luo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Dermatomyositis (DM) and polymyositis (PM) are heterogeneous, chronic and progressive autoimmune disorders characterized by symmetrical, proximal muscle weakness[1,2]. Although the pathogenesis of PM/DM remains unclear, immune intolerance caused by the deficiency of regulatory T (Treg) cells may be an important cause of PM/DM, and quantitative status of peripheral Treg cells is unclear in this disease. Low-dose interleukin-2 (ld-IL2) has been found to enhance proliferation, function and survival of Treg cells to regulate immune tolerance[3]. However, the therapeutic effect of ld-IL2 on PM/DM has not been reported. <h3>Objectives</h3> To investigate whether peripheral Treg cells are reduced and whether ld-IL2 has therapeutic efficacy in PM/DM. <h3>Methods</h3> Total 71 PM/DM inpatients (10 PM and 61 DM) were retrospectively studied. Five PM and 35 DM patients were treated with ld-IL2 (5.0*105 international units (IU) per day for 5 days) accompanied by conventional therapy, while the rest PM/DM patients only with conventional therapy. Thirty of age- and gender-matched healthy adults were regarded as healthy controls (HCs). CD3+T, CD4+T, CD8+T, B, NK, Th1, Th2, Th17 and Treg cells, as well as cytokines [interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-17 (IL-17)] were measured by flow cytometry. The correlation coefficients between various indicators and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) were calculated by Spearman correlation test. <h3>Results</h3> Both PM and DM patients had significantly lower number of CD3+T (<i>P</i>=0.018, <i>P</i>=0.003) and CD4+T cells (<i>P</i>=0.035, <i>P</i>=0.016) than HCs, as well as the number and percentage of Treg cells (<i>P</i>≤0.001) in PM/DM and these of NK, Th1 cells in DM, while Th2 and Th17 cells didn' t exhibit any significant difference. In addition, the ratio of Th1/Th2 in DM (<i>P</i>&lt;0.001) and that of Th17/Treg was obviously decreased in PM/DM (<i>P</i>=0.015, <i>P</i>=0.001). Meanwhile, the production of serum IL-2 was reduced in PM/DM (<i>P</i>≤0.001), while, in contrast, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 increased. ld-IL2 could significantly increase the number of Treg cells but have little effect on Th17 cells in DM. In addition, MYOACT was correlated with the number of CD3+T, CD4+T, CD8+T, Th1, Th2, Treg cells, PLT and lymphocyte (r=-0.388, <i>P</i>=0.002; r=-0.360, <i>P</i>=0.004; r=-0.364, <i>P</i>=0.004; r=-0.386, <i>P</i>=0.002; r=-0.282, <i>P</i>=0.028; r=-0.262, <i>P</i>=0.041; r=-0.311, <i>P</i>=0.015; r=-0.388, <i>P</i>=0.002; respectively) negatively, as well as the percentage of CD3+T and CD8+T cells (r=-0.277, <i>P</i>=0.030; r=-0.291, <i>P</i>=0.023), opposite to aspartate transaminase (AST) (r=0.289, <i>P</i>=0.025) in DM. <h3>Conclusion</h3> The decrease of Treg cells was found in PM/DM accompanied with lower serum IL-2, which should be associated with the pathogenesis of PM/DM. Meanwhile, various pro-inflammatory T cells also showed a downward trend with or without significant difference, indicating PM/DM is caused by immunodeficiency rather than hyperimmunism. ld-IL2 combined with conventional therapy could restore the reduction of CD4Treg cells and help to alleviate disease activity. <h3>References</h3> [1] Yang WM, Chen JJ. Advances in biomarkers for dermatomyositis. Clin Chim Acta 2018; 482: 172-177. [2] Yuan L, Yao L, Zhao L, Xia L, Shen H, Lu J. Serum levels of soluble ST2 and interleukin-33 in patients with dermatomyositis and polymyositis. Clin Exp Rheumatol 2013; 31:428-432. [3] Mizui M, Tsokos GC. Low-Dose IL-2 in the Treatment of Lupus. Curr Rheumatol Rep 2016; 18:68. <h3>Disclosure of Interests</h3> None declared