Deptartment of Rheumatology and Immunology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.
BMC Immunol. 2019 Sep 4;20(1):32. doi: 10.1186/s12865-019-0305-0.
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. 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.
Fifty 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.
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. 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.
ChiCTR-IPR-16009451 Registration date: 2016/10/16.
系统性红斑狼疮（SLE）的发生发展与 Th17 和 Treg 细胞的平衡有关。白细胞介素 2（IL-2）和雷帕霉素（rapamycin）可以影响 Th17 和 Treg 细胞的数量。然而，低剂量的 IL-2 和雷帕霉素是否能缓解 SLE 患者的症状及其机制尚不清楚。本研究旨在分析低剂量 IL-2 联合雷帕霉素对 Treg、Th17 细胞数量及 Th17/Treg 比值的影响，并评估其对难治性 SLE 患者的治疗效果。
共纳入 50 例难治性 SLE 患者和 70 例健康对照者，随访 24 周。结果显示，与健康对照组相比，难治性 SLE 患者的 Treg 细胞数量较低，Th17 细胞数量相似，但 Th17/Treg 比值升高。治疗后患者第 12 周和第 24 周 Treg 细胞数量明显增加，Th17 细胞数量无变化，Th17/Treg 比值在第 6 周和第 24 周均明显降低。治疗后 6、12 和 24 周 SLEDAI 评分均明显降低，治疗后第 6、12 和 24 周泼尼松剂量明显降低。
我们的研究结果支持 Tregs 减少和 Th17/Treg 失衡与难治性 SLE 的发生发展有关。低剂量 IL-2 联合雷帕霉素能恢复 Treg 细胞数量和 Th17/Treg 细胞平衡，诱导免疫耐受，促进疾病缓解，减少泼尼松剂量。
ChiCTR-IPR-16009451，注册日期：2016 年 10 月 16 日。
