原因不明复发性流产Th1/Th2/Th17/Treg免疫失衡的研究

Study on Immune Imbalance of Th1/Th2/Th17/Treg in Unexplained Recurrent Spontaneous Abortion

目的:探讨Th1/Th2/Th17/Treg免疫失衡在原因不明复发性流产(URSA)患者发病机制中的作用。方法:选择URSA患者30例为研究组,自愿终止妊娠的正常健康早孕妇女30例为对照组,Th1、Th2、Th17型细胞因子分别以IFN-γ、IL-4、IL-17为代表,应用ELISA方法检测外周血中IFN-γ、IL-4和IL-17的含量,应用RT-PCR方法检测蜕膜组织中IFN-γ、IL-4和IL-17的表达水平,应用流式细胞技术检测外周血和蜕膜组织中Treg细胞的频率。结果:(1)URSA组血清中IFN-γ和IL-17的含量明显高于对照组(P均<0.05),而血清中IL-4的含量则明显低于对照组(P<0.05)。(2)URSA组蜕膜组织中IFN-γ和IL-17的表达水平明显高于对照组(P均<0.05),而蜕膜组织中IL-4的表达水平则明显低于对照组(P<0.05)。(3)外周血中,URSA组Treg细胞在淋巴细胞中的频率显著低于对照组(P<0.05),在CD4+T细胞中的频率也显著低于对照组(P<0.05)。(4)蜕膜组织中,URSA组Treg细胞在淋巴细胞中的频率显著低于对照组(P<0.05),在CD4+T细胞中的频率也显著低于对照组(P<0.05)。(5)URSA组蜕膜Treg/CD4+T与外周血相比无显著性差异(P>0.05),对照组蜕膜Treg/CD4+T显著高于外周血(P<0.05)。结论:(1)URSA患者外周血及蜕膜中呈现Th1细胞因子(IFN-γ)和Th17细胞因子(IL-17)高表达,Th2细胞因子(IL-4)和Treg细胞低表达,提示URSA患者CD4+T细胞亚群Th1/Th2/Th17/Treg细胞的总体免疫失衡,可能是URSA发生的重要原因。(2)正常妊娠时母胎界面的蜕膜组织中存在Treg细胞积聚现象,URSA发生时母胎界面蜕膜中Treg细胞未表现明显积聚,提示Treg细胞可能是Th1/Th2/Th17/Treg平衡调控的关键点。

Objective： To investigate the role of immune imbalance of Th1 / Th2 / Th17 / Treg in unexplained recurrent spontaneous abortion（ URSA）. Methods： Thirty patients with URSA were involved in study group; Thirty normal pregnant women who want to abort were in control group. IFN-γ stood for Th1 cytokine,IL-4 stood for Th2 cytokine and IL-17 stood for Th17 cytokine. The cytokines levels of IFN-γ、IL-4 and IL-17 in serum were detected by ELISA; the cytokines levels of IFN-γ,IL-4 and IL-17 in decidua were detected by RT-PCR; Treg cells frequencies in serum and decidua were measured by flow cytometry. Results：（ 1） In the serum,the contents of IFN-γ and IL-17 in URSA group were apparently higher than in control group（ P〈0. 05） but the contents of IL-4 in URSA group were apparently lower than in control group（ P〈0. 05）.（ 2） In the decidua,the levels of IFN-γ and IL-17 in URSA group were apparently higher than in control group（ P〈0. 05）,but the levels of IL-4 in study group were apparently lower than in control group（ P〈0. 05）.（ 3）In the serum,the proportions of Treg cells in lymphocytes in URSA group were apparently lower than in control group（ P〈0. 05）,while the proportions of Treg cells in CD4＋T cells in URSA group were apparently lower than in control group（ P〈0. 05）.（ 4） In the decidua,the proportions of Treg cells in lymphocytes in URSA group were apparently lower than in control group（ P〈0. 05）,while the proportions of Treg cells in CD4＋T cells in URSA group were apparently lower than in control group（ P〈0. 05）.（ 5） In URSA group,the proportions of Treg / CD4＋T in decidua were higher than in serum,but there was no significant difference between the two groups（ P〉0. 05）. In control group,the proportions of Treg / CD4＋T in decidua were apparently higher than in serum with a conspicuous otherness（ P〈0. 05）. Conclusion：（ 1） In the patients with URSA,peripheral blood and decidua showed high expression of Th1 and Th17 cell and low expression of Th1 and Treg cells,indicating immune imbalance of CD4＋T Subsets Th1 / Th2 / Th17 / Treg may be one of the important reasons in URSA.（ 2） Treg cell accumulation phenomenon existed in decidua of maternal-fetal interface in gestation age,but Treg cells accumulation disappeared with URSA. This indicates that Treg cells may be the key point for regulation of immune balance of Th1 / Th2 / Th17 / Treg.