SAT0278 LOW-DOSE IL-2 RESTORES TREG-MEDIATED IMMUNE TOLERANCE IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS
Authors: R. Wu, R. Su, T. Ding, H. Xue, J. An, L. Jiang, X. F. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, including granulomatosis with polyangiitis(GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis(EGPA)[1]. Several observations have showed that the breakdown of immune tolerance was involved in the pathogenesis of AAV [2], furthermore, a single, open and clinical trial demonstrates that IL-2 can be used to treat patients with GPA [3]. But there is still a lack of understanding of the relationship between Th17 / Treg and AAV and evidence for the therapeutic effect of IL-2 on AAV, which needs further exploration. Objectives: We first measured the absolute number of CD4+T subsets in peripheral blood of patients to explore the pathogenesis of AAV, and then investigated the effects of short-term and low-dose recombinant human IL-2 (rhIL-2) on CD4+T subsets of patients to analyze the regulatory effect of IL-2 on AAV. Methods: 49 patients with AAV, hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, including 36 patients who were only received conventional glucocorticoids and DMARDs, and other 13 patients who were not only received these treatments but were also injected subcutaneously rhIL-2(50WIU/day for a 5-day course). 31 age and gender-matched healthy adults were selected as controls. The absolute number of Th17 and Treg cells in peripheral blood of health controls and the patients before and after treatment was detected by flow cytometry. Results: There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls (P&lt;0.001) leading to a higher Th17/Treg ratio in the patients with AAV, but there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls. After the treatment of short-term and low-dose IL-2, there was a significant increase in the absolute number of Treg cells (P&lt;0.01) leading to a decrease in the ratio of Th17 and Treg (p&lt;0.05).The absolute number of Th17 had a trend towards higher values but was not statistical significance. Conclusion: The difference of Treg cells between the patients and healthy controls suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response contributing to the pathogenesis of AAV. After the treatment of short-term and low-dose rhIL-2, there was a more significant increase in the absolute number of Treg cells showing that IL-2 could selectively stimulate the growth of Treg cells and restore the Treg-mediated immune tolerance in patients with AAV to achieve disease remission. References: [1]Cosmi, L., Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis. Eur J Immunol, 2017. 47 (4): p. 633-636. [2]Pagnoux, C., Updates in ANCA-associated vasculitis. Eur J Rheumatol, 2016. 3 : p. 122-133. [3]Rosenzwajg, M., et al., Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Annals of the Rheumatic Diseases, 2019. 78 (2): p. 209-217. Disclosure of Interests: None declared