FRI0304 Long-term and low-dose il-2 therapy maintains the th17/treg balance in peripheral blood of patients with primary sjÖgren’s syndrome
Authors: M. Miao, Z. Hao, Y. Guo, X. Zhang, S. Zhang, J. Luo, C. Zhang, X. Zhao, X. Liu, X. Wu, D. Xu, J. Zhao, C. Gao, X. Li
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease mainly affecting exocrine glands. To date, evidence-based guidelines for the management of pSS are lacking. Regulatory T cells (Tregs) are crucial in maintaining immune tolerance and immune homeostasis, but their role in pSS is unclear. Furthermore, low–dose Interleukin-2 (IL-2) has been shown considerable curative effect on expansion of (Tregs) in patients with GVHD. However, the effects of low-dose IL-2 on Tregs and Th17 cells in pSS are not fully elucidated. <h3>Objectives</h3> To explore the long-term effects of low dose IL-2 on Treg cells, Th17 cells and the ratio of them in peripheral blood of Chinese Han patients with primary SjÖgren's syndrome. <h3>Methods</h3> A total of 190 pSS patients consented at enrollment to donate PB samples for comprehensive immune-phenotyping. In the study, BD Trucount tubes with the lyophilized pellet of a known number of internal counting beads were used for determining absolute counts of total CD4<sup>+</sup> T cells in PB and then calculating the absolute number of Th17 cells and CD4<sup>+</sup>Tregs. Eighty eight in 190 were given low-dose recombination human IL-2 (rhIL-2,50 WIU/day for 5 days and then 50WIU/w for several months) by hypodermic injection combined with standard therapy, which includes glucocorticoid, immune-suppressants, biological agents or combination of them, while others (12 in 69) were given standard therapy only. <h3>Results</h3> (<sup>1</sup>The absolute number of Treg cells decreased significantly in peripheral blood of pSS patients compared with that of healthy control.<sup>2</sup>After short period therapy of low dose rhIL-2, Treg cells increased rapidly in one week but decreased to a lower level after one month[20.91 (9, 31.75) vs. 130.31 (65.18, 170.12) vs. 30.37(,<sup>16, 44</sup> p&lt;0.01]. At the same time the ratio of Th17/Treg cells decreased rapidly in one week but increased to a higher level after one month[0.23 (0.19, 0.33) vs. 0.09 (0.04, 0.18) vs. 0.18 (0.14, 0.69), p&lt;0.1].<sup>3</sup>Long-term IL-2 could maintain the higher level of CD4Treg cells and the balance of Th17/Treg.<sup>4</sup>Patients with balanced Th17/Treg have more obvious improvement of symptoms and more significantly decreased dose of glucocorticoid and HCQ compared with standard therapy group. <h3>Conclusions</h3> Therapy of low dose rhIL-2 could promote the proliferation of Treg cells and rebuild the balance of Th17/Treg for both short and long term. To rebuild the balance of Th17/Treg for long-term, we should use IL-2 for a long time. Balance of Th17/Treg cells in pSS patients predicts a good prognosis. <h3>References</h3> [1] Adamson TC 3rd. Immunohistologic analysis of lymphoid infiltrates in primary Sjogren's syndrome using monoclonal antibodies. J. Immunol. 1983;130:203–208. [2] Lowand HZ, Witte T. Aspects of innate immunity in Sjogren's syndrome," Arthritis Research and Therapy. Arthritis Res Ther2011;13:218. [3] Sudzius G, et al. Distribution of Peripheral Lymphocyte Populations in Primary Sjögren's Syndrome Patients. J. Immunol. Res. 2015;854706. <h3>Disclosure of Interest</h3> None declared