OP0043 The number of circulating regulatory t cells is reduced and low-dose il-2 selectively stimulates its proliferation in patients with systemic lupus erythematosus
Authors: X Liu, X Jing, X Wu, J Wang, Z Liang, M Hao, J Chen, C Gao, X Li
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The imbalance of T help 17 cells (Th17)/regulatory T cells (Tregs) is considered to be a pivotal cause of autoimmune diseases<sup>1</sup>, including systemic lupus erythematosus (SLE). However, previous reports<sup>1,2</sup> describing the respective changes of Tregs and Th17 cells in SLE patients were controversial because a few samples or diverse markers were used to identify Tregs with little consensus. <h3>Objectives</h3> To clarify the status of Tregs and Th17 in SLE, we investigated the frequencies of Tregs and Th17 cells on a large scale and whether those defects can be corrected by the supplementation of low-dose human recombinant interleukin-2 (IL-2). <h3>Methods</h3> Two hundred and thirty-five SLE patients (219 women and 16 men), with mean age of 37.80±14.00 years, were enrolled. The disease activity using European League Against Rheumatism (EULAR) criteria was judged for SLE patients with erythrocyte sedimentation rate (ESR) and SLEDAI scores. The frequencies of CD3+CD4+FOXP3+Treg cells and Th17 cells in peripheral blood from these patients were measured by flow cytometry. And low-dose IL-2 was used among 127 patients at a dosage of fifty WIU every day for five days. Immunological and clinical assessments were performed again at the end of IL-2 treatment. Ninety healthy volunteers, matched for patients9 age and gender, were also included for the estimation of CD4+ T cell subsets. <h3>Results</h3> As compared to healthy controls (median of Treg cells: 33.09 cells/ul), the frequencies of circulating CD4+CD25+FOXP3+Treg cells were significantly decreased in SLE patients (median: 15.49 cells/ul, <i>P</i>&lt;0.001). The median ratios of Th17/Tregs cells in patients were greatly higher than those of healthy volunteers [0.42 (0.19, 0.88) vs. 0.21 (0.15, 0.34), <i>P</i>&lt;0.001]. There was not significantly different in circulating Th17 cell between two groups. Moreover, CD4+CD25+FOXP3+Treg cells were negatively correlated with ESR and SLEDAI score (r=-0.198, <i>P</i>=0.01; r=-0.25, <i>P</i>=0.002).While no obvious correlation was seen between Th17 cells and SLEDAI score. After IL-2 therapy in SLE, there was a four-fold increase in circulating CD4+CD25+FOXP3+Treg cells [43.73 (24.08,74.22) vs. 11.95 (7.51,20.34),<i>P</i>&lt;0.001], whereas Th17 cells were increased slightly. The ratio of Th17/Tregs was decreased significantly in patients with IL-2 treatment [0.19 (0.09,0.41) vs. 0.52 (0.23,0.95),<i>P</i>&lt;0.001], tended to balance and had no difference with healthy individual (<i>P</i>=0.275). <h3>Conclusions</h3> With the increase of disease activity,CD4+CD25+FOXP3+Treg cells were gradually reducing, while Th17 cells did not show a significant change, indicating that the reduction of Tregs but not the elevation of Th17 cells may be the major reason for imbalance of Th17/Tregs. It is speculated that SLE is an autoimmune disease triggered by the defect of immunotolerance. More importantly, low-dose IL-2 selectively modulated the abundance of Tregs, which effectively induced autoimmune tolerance and further improved clinical symptoms. <h3>References</h3> Ji Y, Xue Y, Hejian Z, et al.Recovery of the immune balance betweenTh17 and regulatory T cells as a treatment for systemic lupus erythematosus[J]. Rheumatology 2011;50:1366–1372. Steinmetz OM, Turner JE, Paust HJ et al. CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis[J]. J Immunol 2009;183:4693–704. <h3>Disclosure of Interest</h3> None declared