SAT0370 IMBALANCE OF TH17 AND REGULATORY T CELLS IN PATIENTS WITH PSORIATIC ARTHRITIS AND RE-BALANCE BY LOW-DOSE IL-2
Authors: Sheng-xiao Zhang, Yu-Fei Hao, Jia Wang, He-Hua Sun, Guang-Ying Liu, Chong Gao, Caihong Wang, LI Xiao-Feng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Psoriatic arthritis (PsA) is an T lymphocytes-mediated inflammatory condition <sup>[</sup><sup>1</sup><sup>]</sup>. Although regulatory T cells (Tregs) isolated from blood and psoriatic skin have been showed a functional deficiency in suppressing effector T-cells in PsA<sup>[</sup><sup>2</sup><sup>]</sup>, absolute quantitative status of peripheral Treg or Th17 cells is still unclear. On the other hand, recent studies have revealed that low-dose IL-2 alleviate<b>s</b> some of autoimmune disease activity by upregulating Treg cells <sup>[3,4]</sup>, which is expected to control the development of PsA. <h3>Objectives</h3> To assess the absolute numbers of peripheral lymphocyte subpopulations and the efficacy and safety of low-dose IL-2 therapy in PsA patients. <h3>Methods</h3> Total 95 PsA patients and 106 age-and sex-matched healthy controls were recruited. Of them, 22 cases received the treatment of low-dose IL-2 at 0.5 million IU per day for 5 days subcutaneously. The absolute numbers of lymphocyte subgroups and CD4<sup>+</sup>T subsets in peripheral blood were measured by flow cytometry. The clinical manifestations and laboratory indicators as well as the levels of peripheral lymphocyte and CD4<sup>+</sup>T subsets were compared before and after the treatment. <h3>Results</h3> Notably, the absolute numbers of lymphocyte subpopulations in peripheral blood such as NK, CD4<sup>+</sup>T, Th17 and Tregs in PsA patients were lower than those of healthy controls (<i>P</i>&lt;0.05). The absolute number of Treg was significantly and negatively correlated with the levels of disease indicators, including DAS28, the number of tender joints, visual analogue scale, physician's global assessment, dermatology life quality index, and health assessment questionnaire (<i>P</i>&lt;0.05). After low-dose IL-2 treatment, compared with the baselines, there was a significant increase in the absolute numbers of NK (<i>P</i>&lt;0.05), CD4<sup>+</sup>T (<i>P</i>&lt;0.01), Th17 (<i>P</i>&lt;0.01) and Treg cells (<i>P</i>&lt;0.001). Interestingly, IL-2 markedly raised the level of Tregs in PsA patients even higher than that of healthy donors (<i>P</i>&lt;0.001), leading to re-balance of Th17 and Tregs. Further, low-dose IL-2 treatment rapid reduced the disease activity such as DAS28, the number of tender joints, visual analogue scale, physician's global assessment, dermatology life quality index, and health assessment questionnaire (<i>P</i>&lt;0.05). <h3>Conclusion</h3> Patients with PsA had an imbalance between pro- and anti-inflammatory cells, particularly the reduction of the absolute number of Tregs. Low-dose IL-2 combination treatments restored the decreased number of Treg cells and lowered disease activity indicators of these patients without over-treatment and evaluable side effect. Further studies are needed to evaluate the long-term immunoregulatory ability of IL-2 treatment. <h3>References</h3> [1] Gossec L, Coates LC, de Wit M, et al. Management of psoriatic arthritis in 2016: a comparison of EULAR and GRAPPA recommendations[J]. Nature reviews Rheumatology, 2016, 12(12):743-750.doi:10.1038/nrrheum.2016.183. [2] Szentpetery A, Heffernan E, Gogarty M, et al. Abatacept reduces synovial regulatory T-cell expression in patients with psoriatic arthritis[J]. Arthritis research &amp; therapy, 2017, 19(1):158.doi:10.1186/s13075-017-1364-3. [3] Jeffery HC, Jeffery LE, Lutz P, et al. Low-dose interleukin-2 promotes STAT-5 phosphorylation, Treg survival and CTLA-4-dependent function in autoimmune liver diseases[J]. Clinical and experimental immunology, 2017, 188(3):394-411.doi:10.1111/cei.12940. [4] Miao M, Hao Z, Guo Y, et al. Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjogren's syndrome[J]. Annals of the rheumatic diseases, 2018, 77(12):1838-1840.doi:10.1136/annrheumdis-2018-213036. <h3>Disclosure of Interests</h3> None declared