We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP). Eighty-eight patients were separated into the control (cyclosporine A plus prednisone) and experimental (rapamycin plus prednisone) groups. The CD4+CD25+CD127low regulatory T (Treg) cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR) was similar in both groups (experimental group versus control group: 58% versus 62%, ). However, sustained response (SR) was more pronounced in the experimental group than in the control group (68% versus 39%, ). Both groups showed similar incidence of adverse events (7% versus 11%, ). As expected, the low pretreatment baseline level of Treg cells was seen in all patients ( ); however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP. 1. Introduction Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by an autoantibody-mediated destruction and impaired platelet production. Recently, it has become evident that the impairment of Treg cells may contribute to the development of ITP [1–4]. They play a critical role in the maintenance of peripheral tolerance by suppressing self-reactive lymphocytes. Once these regulating cells are impaired, patients have activated autoreactive T cells against platelet and imbalanced cytokine production, which accelerate the destruction of platelets [5–7]. Given the defective function or low cell numbers of Tregs in patients with ITP, expansion of the functional Treg cells represents an interesting therapeutic approach. In addition, some clinical studies have demonstrated that the effective treatments for ITP can improve the Treg cells level after the platelet count is recovered [8–11]. Although the exact mechanism is not fully understood, these results suggest a promising possibility that Treg cells could be a potential biomarker to therapies in the future. Rapamycin, as an immunosuppressant, has been used safely and effectively to treat renal transplant rejection since 1999 [12]. By inhibiting the intracellular kinase mTOR, rapamycin can selectively expand the functional Treg cells [13–17]. These expanded Treg cells suppress
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