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通过雷帕霉素和全反式维甲酸恢复系统性红斑狼疮患者的辅助性 T 细胞 17/调节性 T 细胞平衡并降低疾病活动度。

Restoring T-helper 17 cell/regulatory T-cell balance and decreasing disease activity by rapamycin and all-trans retinoic acid in patients with systemic lupus erythematosus.

机构信息

Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University, Taiyuan, PR China.

出版信息

Lupus. 2019 Oct;28(12):1397-1406. doi: 10.1177/0961203319877239. Epub 2019 Sep 24.

DOI:10.1177/0961203319877239
PMID:31551029
Abstract

OBJECTIVE

This study aimed to investigate the effect of rapamycin (RAPA) alone or in combination with all-trans retinoic acid (ATRA) on the T-helper 17 (Th17) cell/regulatory T-cell (Treg) balance in patients with systemic lupus erythematosus (SLE) and to evaluate the clinical efficacy.

METHODS

Seventy patients with SLE were enrolled. They were randomly and equally divided into RAPA and RAPA + ATRA groups. The number of Th17 and Treg cells was measured by flow cytometry before and after treatment for 6, 12 and 24 weeks. The SLE Disease Activity Index (SLEDAI) score and the prednisone dose before and after treatment were used to evaluate the efficacy between the two groups.

RESULTS

In both groups, at different time points after treatment, the number of Th17 cells ( = 0.003) and Th17/Treg ratio ( = 0.044) reduced, while the number of Treg cells ( = 0.574) tended to increase. The SLEDAI score and the dose of prednisone decreased significantly ( < 0.001). There was no significant difference in the number of Th17 cells ( = 0.089), Treg cells ( = 0.059), Th17/Treg ratio ( = 0.580), SLEDAI score ( = 0.127) and the dose of prednisone ( = 0.329) between the two groups.

CONCLUSION

Disease activity in SLE patients reduced with RAPA alone or in conjunction with ATRA, reducing glucocorticoid requirement. One of its mechanisms of action may be regulating the Th17/Treg cell balance, which provides a new model for the pathogenesis and potential treatment of SLE.

摘要

目的

本研究旨在探讨雷帕霉素(RAPA)单独或与全反式维甲酸(ATRA)联合应用对系统性红斑狼疮(SLE)患者辅助性 T 细胞 17(Th17)/调节性 T 细胞(Treg)平衡的影响,并评估其临床疗效。

方法

纳入 70 例 SLE 患者,随机分为 RAPA 组和 RAPA+ATRA 组,每组 35 例。分别于治疗前及治疗后 6、12、24 周,采用流式细胞术检测 Th17 及 Treg 细胞数量,采用 SLE 疾病活动指数(SLEDAI)评分和治疗前后泼尼松剂量评估两组疗效。

结果

两组患者在治疗后不同时间点,Th17 细胞数量( = 0.003)及 Th17/Treg 比值( = 0.044)降低,Treg 细胞数量( = 0.574)呈升高趋势,SLEDAI 评分及泼尼松剂量明显降低( < 0.001)。两组患者 Th17 细胞数量( = 0.089)、Treg 细胞数量( = 0.059)、Th17/Treg 比值( = 0.580)、SLEDAI 评分( = 0.127)及泼尼松剂量( = 0.329)比较,差异均无统计学意义。

结论

RAPA 单独或联合 ATRA 治疗可降低 SLE 患者的疾病活动度,减少糖皮质激素的需求,其作用机制之一可能是通过调节 Th17/Treg 细胞平衡,为 SLE 的发病机制和潜在治疗提供了新的模型。

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