FRI0171 THE CHANGES OF IMMUNE FUNCTION AND CLINICAL INDEXES WITH SYSTEMIC LUPUS ERYTHEMATOSUS AFTER IMMUNOREGULATORY COMBINATION THERAPIES
Authors: X. Liu, X. Liu, H. Hou, X. LI
Journal: Annals of the Rheumatic Diseases (2020)

Background: Recent studies have reported that some drugs such as low-dose interleukin-2, rapamycin, metformin, retinoic acid and coenzyme Q10 could promote the proliferation and functional recovery of regulatory T cells (Treg) in patients with autoimmune diseases. However, the effects on the balance of Treg cells and pro-inflammatory lymphocytes and long-term efficacy have rarely been reported. Objectives: To evaluate the changes of peripheral lymphocyte subsets, conventional drugs and remission rate in patients with systemic lupus erythematosus (SLE) after immunomodulatory combination therapies. Methods: A total of 189 patients with SLE from the Second Affiliated Hospital of Shanxi Medical University from January 2016 to October 2019 were enrolled, who were divided into well-controlled group and untargeted control group taking a full consideration of the patient’s symptoms, signs and related laboratory findings. We measured the absolute counts of B, NK, CD8+T and helper T 1 (Th1), helper T 2 (Th2), helper T 17 (Th17) and Treg cells in peripheral blood of patients before immunomodulatory combination therapies and during the 3 months and 6 months of follow-up and 190 sex- and age- matched control individuals using flow cytometry. Moreover, the ratios of various cells to Treg cells were calculated. Results: Compared with healthy controls, Treg cells in SLE patients were significantly lower before the treatment with immunomodulator, while the ratios of various pro-inflammatory lymphocytes to Treg cells (such as Th2/Treg, Th17/Treg, CD8+T/Treg, etc.) were higher. After 3 months and 6 months with immunomodulatory therapy, the absolute number of Treg cells in peripheral blood of SLE patients increased obviously reaching to normal level. Accordingly, the ratios of various pro-inflammatory lymphocytes to Treg cells recovered. At the same time, the dose of glucocorticoid and disease-modifying antirheumatic drugs (DMARDs) decreased distinctly. Additionally, the well-controlled group was able to maintain a high remission rate, and the untargeted control group could achieve a higher response rate after immunomodulatory treatment. Conclusion: The imbalance between pro-inflammatory lymphocytes and Treg cells caused by the significant decrease of Treg cells may be the main cause of SLE. And immunomodulatory combination therapies we came up with may reverse the imbalance of proinflammatory lymphocytes and Treg cells, which is an potential and effective treatment for SLE. References: [1]Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory disease[J]. Autoimmun Rev, 2014, 13(6): 668-677. [2]Yu A, Snowhite I, Vendrame F, et al. Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes. Diabetes. 2015;64: 2172–2183. [3]Schuiveling M, Vazirpanah N, Radstake TRDJ, Zimmermann M, Broen JCA. Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?[J]. Curr Drug Targets, 2017;18:1-15. Table 1. The changes of remission rate in the no-remission group during follow-up. Follow-up period Total patients Remission No-remission Remission rate(%) Baseline 92 0 92 0 3 Months 72 33 39 45.8 a 6 Months 74 42 32 56.8 a a: Compared with baseline; b: Compared with 3 months. Acknowledgments: We would like to express our sincere gratitude to all our coworkers and collaborators, Jing Luo, Xiangcong Zhao, Chen Zhang, Qi Wu, Congcong Liang, and Rui Fu for their technical support. Disclosure of Interests: None declared