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THU0377 Low dose il-2 therapy can recovery th17/treg cell balance in patients with spondyloarthropathy through increasing regulatory t cells numbers
  1. F Jinnan1,
  2. X Dan1,
  3. C Qianqian1,
  4. Q Kaili1,
  5. G Chong2,
  6. L Xiaofeng1
  1. 1Department of Rheumatology, The Second Hospital of Shanxi medical University, Taiyuan, China
  2. 2Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Boston, American Samoa

Abstract

Background The imbalance in the number of Th17 and Treg cells is suggested to be associated with the pathogenesis of SpA. Recent studies have shown that interleukin-23 (IL-23) and Th17 play a crucial role in the pathogenesis of SpA. However the status of CD4+CD25+Foxp3+Treg cells which exert immunoregulatory functions are remains to investigate.

Objectives To explore the status of the immunologic balance between Th17 cells and Treg cells in patients with SPA, and to assess the effect of low dose IL-2 on the peripheral CD4+ T cells.

Methods Two hundred and two patients, who met the Assessment of Spondyloarthritis International Society (ASAS) criteria were enrolled and given conventional therapy, including Nonsteroidal Anti-inflammatory Drugs (NSAIDs), biological agents, Sulfasalazine, glucocorticoid. Eighty seven patients were not only given conventional therapy, but also injected subcutaneously low-dose IL-2 (50 WIU/day for 5 days). Clinical and laboratory indicators were compared before and after IL-2 treatment. The CD4+ T cells in peripheral blood were measured by multicolor flow cytometry. The side effects were observed in the course of therapy.

Results The absolute number and ratio of CD4 + CD25 + FOXp3 + regulatory T cells in peripheral blood of patients with SPA was significantly decreased compared with the healthy control group, (25.13 (18.76,37.37) vs. 33.06 (22.87,42.33), P<0.001); Th17/Treg (0.29 (0.18, 0.49) vs. 0.20 (0.15, 0.34), P=0.001). The absolute number of Treg cells increased more than 3-times (22.70 (14.47, 30.10) vs.67.87 (48.21, 105.82), p<0.001) after 5 days of low-dose IL-2 treatment. Th17/Treg was significantly higher (0.32 (0.18, 0.57) vs. 0.20 (0.15, 0.34), P<0.001) before treatment compared with healthy controls.

Conclusions The decrease of CD4 + CD25 + FOXp3 + Treg cells might play a key role in the pathogenesis of SpA. Low dose IL-2 therapy can restore and maintain the balance of Th17 and Treg cells by increasing Treg cells numbers selectivity. The therapy is safe. More attention should be paid on the long term benefits of low-dose IL-2 therapy in the further research.

References

  1. Wu Y, Ren M, Yang R, Liang X, Ma Y, Tang Y, et al. Reduced immunomodulation potential of bone marrow-derived mesenchymal stem cells induced CCR4 + CCR6 + Th/Treg cell subset imbalance in ankylosing spondylitis. Arthritis Res Ther. 2011;13:R29.

  2. Jandus C, Bioley G, Rivals JP, Dudler J, Speiser D, Romero P. Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58:2307–17.

  3. Wendling D, Guillot X, Prati C. The IL-23/Th 17 pathway in spondyloarthritis: the royal road. Joint Bone Spine 82(1), 1–4 (2015).

References

Disclosure of Interest None declared

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