AB0536 Rapamycin attenuates symptom and restores the balance of th17/treg in refractory primary sjogren’s syndrome

Background Primary Sjogren’s syndrome (pSS) is one of the more common rheumatological diseases. Despite continued advances, the use of conventional drugs or biologic agents in patients with pSS did not provide expected efficacy and a targeted treatment of pSS is not available at present. We have shown that absolute number of peripheral CD4 + CD25 + FOP3 + regulatory T cells (Tregs) decreased in pSS patients. And rapamycin is an inhibitor of mTOR that can decrease Th17 cells but increase regulatory T cells (Treg cells). Objectives To observe the effect of rapamycin on Th17/Treg cell balance in patients with refractory pSS. Methods Twenty-eight refractory SS patients (26 women and 2 men) and 93 health controls were enrolled, with a mean duration of 76.64±49.66 months and mean age of 52.39±10.62 years. They fulfilled the 2002 PSS international classification criteria and were treated with glucocorticoid and immunosuppressant for more than one year, but had not yet reached the disease relief. After the eligible patients are given rapamycin in combination with conventional therapy at 0, 12, 24 weeks, we respectively collect the clinical symptoms, blood routine, urine routine, ESR, the absolute number of Th17 and Treg cells, the ratio of Th17/Treg, and the dosage of corticosteroids and immunosuppressant. Alleviation criteria: no clinical symptoms, inflammation normal range, no organ damage. Results The absolute number of Treg cells decreased significantly in peripheral blood of pSS patients compared with that of healthy controls. By rapamycin combined with conventional therapy, flow cytometry showed the absolute number of Treg cells in refractory SS patients was increased from 25.51 cells/µl (at week 0) to 27.88 cells/µl (at 12 weeks) and 29.6 cells/µl (at 24 weeks) (P>0.05) respectively. The ratio of Th17/Treg decreased from 0.38 (at week 0) to 0.21 (at 12 weeks) and 0.22 (at 24 weeks) (P>0.05). There was no significant difference in the usage of prednisone, whereas 5 patients gradually stopped using CTX at 24 weeks. Also, the dose of hydroxychloroquine and leflunomide were markedly diminished. Conclusions Our results suggest that rapamycin combined with the conventional treatment greatly alleviated symptoms of patients with pSS, and gradually reduced the use of DMARDs. The absolute number of peripheral Tregs decreased in pSS patients and restored by this combined therapy. It still needs to be further confirmed by large sample studies. References [1] Ferro F, Marcucci E, Orlandi M, Baldini C, Bartoloni-Bocci E. One year in review 2017: primary Sjogren’s syndrome. Clin Exp Rheumatol2017Mar–Apr;35(2):179–191. Epub 2017 Mar 15. Review.PMID: 28337967. [2] Zheng Y. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. [J].Immunity2009;30(6):832–844. Acknowledgements Wuruijie contributed collection of information of outpatients. Wuqi contributed contacted and bought reagents. Disclosure of Interest None declared