Abstract
BackgroundThe development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients.ResultFifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased.ConclusionOur results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage.Trial registrationChiCTR-IPR-16009451 Registration date: 2016/10/16
Highlights
The development of Systemic lupus erythematosus (SLE) has been associated with the balance of T-helper 17 cells (Th17) and Regulatory T cells (Treg) cells
Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE
Changes in disease activity indicators, Th17, Treg, Th17/ Treg, prednison and DMARDs in patients with refractory SLE during the follow-up period Low-dose IL-2 combined with rapamycin increased Treg cells population in refractory SLE patients Since it is known that low-dose IL-2 and rapamycin can increase the proportion of Treg cells, we assessed the effect of the combined treatment in patients with refractory SLE
Summary
The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells It is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. We aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients. Recent studies found that low dose of IL-2 can promote the number of Treg in T1D [4], HCV-induced vasculitis [5], GVHD [6, 7] and alopecia areata [8]. Low dose of IL-2 can increase the
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