Abstract

Aim

The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels.

Methods

Women with RIF received oral HCQ (n = 60) on day 4 of the menstrual cycle and continued until day 20 of the menstrual cycle and 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days in another cycle. The serum levels of IL-17 and IL-10, the expression of transcription factors related to Th17 and Treg cells and the immune-reactivity of IL-17, IL-21 as Th17 related cytokines and IL-10, TGF- β as Treg related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively.

Results: Treatment with HCQ down-regulated Th17 related cytokines and function and up-regulated Treg related cytokines and function significantly (p < .001). RORγt, the Th17 transcription factor, expression was down-regulated and FOXP-3, the T-reg transcription factor, expression was up-regulated. The biochemical pregnancy rate was not significantly different in RIF patients before and after treatment.

Conclusion

Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.

中文翻译：

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羟氯喹治疗对反复植入失败女性Th17 / Treg比值调节和妊娠结局的影响：临床试验

摘要

目标

最近有人提出Th17 / Treg细胞的失衡是复发性植入失败（RIF）的新危险因素。此外，Th17 / Treg细胞还参与了RIF患者外周血和子宫内膜组织的免疫调节。在这项研究中，我们调查了羟基氯喹（HCQ）对RIF妇女Th17和Treg细胞水平和功能的影响。通过调节高细胞因子水平可以改善妊娠结局。

方法

患有RIF的女性 在月经周期的第4天接受口服HCQ（n = 60），并一直持续到月经周期的第20天和胚胎移植前2天，并一直持续到妊娠试验的那一天，共16天。另一个周期。血清IL-17和IL-10水平，与Th17和Treg细胞相关的转录因子的表达以及IL-17，IL-21作为Th17相关细胞因子和IL-10，TGF-β作为Treg的免疫反应分别通过ELISA，实时荧光定量PCR和荧​​光免疫组织化学方法评估子宫内膜组织中的相关细胞因子。

结果：用HCQ治疗可显着下调Th17相关细胞因子和功能，而上调Treg相关细胞因子和功能（p  <.001）。Th17转录因子RORγt的表达下调，T reg转录因子FOXP-3的表达上调。RIF患者治疗前后的生化妊娠率无显着差异。

结论

我们的结果表明，怀孕期间免疫细胞异常的RIF妇女服用HCQ可能会影响Th17 / Treg比率并增强Treg并减少Th17反应，这可能与成功的妊娠结局有关。但是，在本研究中未观察到妊娠结局的显着差异。