AB0382 Rapamycin selectively increases circulating tregcellsand maintain remission of patients with rheumatoid arthritis

Background It is thought that Rheumatoid arthritis (RA) arises from a breakdown in immunological self-tolerance. We have givena direct evidence for this conceptionthat absolute number of peripheral CD4+Regulatory T-cells (Tregs) decreased inRA patients[1]. Furthermore, rapamycin can significantly induce immune tolerance through up-regulate Tregs and down-regulate Th17 cells[2]. Objectives To investigate the effect of rapamycin on the absolute numbers of Th17 and Treg cells and on maintenance of disease remission in RA patients instead of DMARDs. Methods Thirty-two patients, who achieved remission(DAS28 ≤2.6) by the treatment with two kinds of DMARDs for more than half a year, received rapamycin at a dose of 0.5 mg every other dayfor 12 weeks. Before and after treatment with rapamycin, thediseaseactivity and immunological assessments of them were performed. In this 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+ T cells in peripheral blood and then calculating the absolute number of Th17 cells and CD4+Tregs. Results At week 12, 65.6% of the patients maintained remission (DAS28 ≤2.6). TheDAS28 was increased from a median of 2.03(at week 0) to 2.15(at week 12) (p>0.05). The absolute numberof Treg cells was increased significantly from a median of 22.16(at week 0) to 32.19(at week 12) (P=0.039). The absolute number of Th17 cells was decreased from a median of5.98(at week 0) to 5.56(at week 12) (p>0.05). The ratio of Th17/Treg cells was also decreased from a median of 0.245(at week 0) to 0.19(at week 12) (p>0.05). At the same time, the mean dosage of prednisone decreased from 6.29 mg/d to 5.35 mg/d and thatof DMARDs were also reduced from93.75% to 56.25%. Conclusions Rapamycin was effective in the maintenance of remission(DAS28 ≤2.6)by increase of Treg cells and correcting the imbalance of Th17/Treg cells. Meantime, the mean dosage of conventional drugs such as glucocorticoid and DMARDs gradually decreased. In the future, rapamycin may replace current immunosuppressant for treatment of RA. References [1] Niu H, Li Z, He J, et al. Rapamycin selectively increases circulating Treg cells and modulates the imbalance of Th17/Treg cells in patients with low active rheumatoid arthritis. [2] Yang X, Yao Q, Hu X, et al. Rapamycin-conditioned dendritic cells induced immune tolerance through the regulation of Treg/Th17 cells in mice. Zhonghua Yi Xue Za Zhi2015Aug 11;95(30):2469–73. Disclosure of Interest None declared