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Background: Although regulatory T cells (Tregs) play crucial roles in the maintenance of immune hemostasis, the numbers of peripheral Tregs in patients with psoriatic arthritis (PsA) remain unclear. We measured these numbers and the efficacy and safety of low-dose interleukin-2 (IL-2) therapy. Methods: We recruited 95 PsA patients, of whom 22 received subcutaneous low-dose IL-2 [0.5 million international units (MIU) per day for 5 days] combined with conventional therapies. The absolute numbers of cells in peripheral CD4+ T cell subsets were measured via modified flow cytometry. Clinical and laboratory indicators were compared before and after treatment. Results: PsA patients had lower peripheral Treg numbers than healthy controls ( p < 0.01), correlating significantly and negatively with the levels of disease indicators ( p < 0.05). Although low-dose IL-2 significantly increased the Th17 and Treg numbers in PsA patients compared with the baseline values, the Treg numbers rose much more rapidly than those of Th17 cells, re-balancing the Th17 and Treg proportions. Low-dose IL-2 combination therapy rapidly reduced PsA disease activities as indicated by the DAS28 instrument, thus the number of tender joints, visual analog scale pain, physician global assessment, the dermatology life quality index score, and the health assessment questionnaire score (all p < 0.05). Conclusion: PsA patients exhibited low Treg numbers. Low-dose IL-2 combination treatment increased these numbers and relieved disease activity without any apparent side effects. Additional studies are required to explore the long-term immunoregulatory utility of IL-2 treatment.

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BackgroundDermatomyositis (DM) and polymyositis (PM) are rare chronicinflammatory disorders with significant associated morbidityand mortality despite treatment [1, 2], characterized by subacute onset of proximal muscle weakness, elevated muscle enzymes, and inflammatory infiltrates on muscle biopsy. Although several hypotheses have been proposed for triggers of inflammation in the diseases [3], growing evidences have focused on the immune disorders [4]. However, the quantitative changes of lymphocyte subsets in DM/PM are unclear and whether low-dose IL-2 could rebalance the lymphocyte subsets and further benefit to remission disease activity of DM/PM patients is unknown.ObjectivesTo investigate the quantitative status of peripheral blood lymphocyte subsets in the patients for the exploration of pathogenesis and evaluate the safety and efficacy of low-dose IL-2 therapy in patients with DM/PM.MethodsFrom February 2016 to October 2018, total 147 patients with PM/DM and 128 gender and age matched healthy individuals were enrolled in this study. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and Treg cells in peripheral blood of these individuals were detected by flow cytometry combined with standard absolute counting beads. Patients in IL-2 group (n=31) were not only given traditional treatments, but injected subcutaneously human IL-2 (aldesleukin) at 50 WIU per day for a 5-day course. The demographic features, clinical manifestations and laboratory indicators were compared before and after the treatment.ResultsPatients with PM/DM had lower levels of Treg cells as well as T, CD4+T, CD8+T, Th1, Th2, and Th17 compared with those of the healthy controls (P < 0.05), which was correlated with disease activity(P < 0.05). After IL-2 administration, the absolute numbers of peripheral lymphocyte subsets in patients were significantly increased (P < 0.05), leading to a better remission compared with the patients received conventional therapy (P < 0.05).ConclusionThe difference status of peripheral lymphocyte subsets, especially Tregs, between PM/DM patients and healthy individuals suggests that lymphocyte subsets may be involved in and play an important role in the pathogenesis of patients. Low-dose IL-2 can effectively increase the level of Treg cells as well as other lymphocytes to some degree and maintain the immunologic balance, which may help for PM/DM patients’ symptoms remission without over-treatment and evaluated side effect. But long-term benefits of IL-2 therapy are required to further study.References[1] Erin, V. and L. T. Sarah, et al. (2015). “The evidence for immunotherapy in dermatomyositis and polymyositis: a systematic review.” Clin Rheumatol 34 (12): 2089-95.[2] Thomas, B. and F. Romain, et al. (2018). “Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis.” Autoimmun Rev.[3] Angela, C. and D. S. Maria, et al. (2017). “The Immune Response and the Pathogenesis of Idiopathic Inflammatory Myositis: a Critical Review.” Clin Rev A...