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复发性流产患者血清细胞因子(IL-6、IL-10 和 TGF-β)及 CD4CD25FOXP3Treg 细胞群水平。

Circulating levels of cytokines (IL-6, IL-10 and TGF- β) and CD4CD25FOXP3Treg cell population in recurrent pregnancy loss.

机构信息

School of Sciences (Zoology), Maulana Azad National Urdu University, Gachibowli, Hyderabad 32, Telangana, India.

Gynaecology and Obstetrics Department, Niloufer Hospital, Hyderabad, Telangana, India.

出版信息

Reprod Biol. 2024 Mar;24(1):100842. doi: 10.1016/j.repbio.2023.100842. Epub 2024 Jan 3.

Abstract

Recurrent pregnancy loss (RPL), a serious reproductive health issue, characterized by two or more pregnancy losses before 20th week of gestation. Globally, it affects 2-5% couples and the basis of the crisis is still unknown in 50% cases. Successful pregnancy is associated with pro and anti-inflammatory gestational phases that tolerate the semi-allogenic foetus, and disturbance leads to pregnancy complications like RPL. This case-control study aimed to assess the inflammatory status in the mid-gestation of ongoing pregnancy of women with (RPL) and without (NRPL) the history of RPL. Blood samples were processed for PBMC isolation, subjected to Flow-cytometry for CD4CD25FOXP3Treg-cell population count and serum samples for IL-6, TGF-β, IL-10 cytokine levels (ELISA). Significant reduction in the percentage of Treg cells, and elevated values for IL-6/TGF-β and IL-6/IL-10 ratios were observed in RPL over NRPL group (p = 0.0001). Opposing results were seen with respect to the magnitude of history of RPL (2 vs. >2 losses). ROC curve analysis showed the superior discriminatory ability of cytokine ratios (IL-6/TGF-β > IL-6/IL-10) for RPL over Treg cells. Our findings are suggestive of pro-inflammatory dominance in mid-gestation of pregnant women with a history of RPL in general and greater than normal anti-inflammatory milieu in cases with > 2 pregnancy loss. As both sterile and infection related inflammation plays a role in pregnancy loss, studies enrolling women with favourable and unfavourable ongoing pregnancies may shed light on the importance of the present study for developing better management/therapeutic strategies.

摘要

复发性流产(RPL)是一种严重的生殖健康问题,其特征是在妊娠 20 周前发生两次或两次以上的妊娠丢失。在全球范围内,它影响 2-5%的夫妇,而在 50%的病例中,其根本原因仍不清楚。成功的妊娠与促进和抑制炎症的妊娠阶段有关,这些阶段可以耐受半同种异体胎儿,而干扰会导致妊娠并发症,如 RPL。本病例对照研究旨在评估有(RPL)和无(NRPL)RPL 病史的孕妇中期妊娠的炎症状态。处理血样以分离 PBMC,进行流式细胞术以计数 CD4CD25FOXP3Treg 细胞群体,并检测血清样本中的细胞因子 IL-6、TGF-β、IL-10 水平(ELISA)。在 RPL 组中观察到 Treg 细胞的百分比显著降低,而 IL-6/TGF-β 和 IL-6/IL-10 比值升高(p=0.0001)。而对于 RPL 病史的严重程度(2 次与>2 次丢失)则观察到相反的结果。ROC 曲线分析显示,细胞因子比值(IL-6/TGF-β>IL-6/IL-10)对 RPL 的判别能力优于 Treg 细胞。我们的研究结果表明,一般来说,有 RPL 病史的孕妇在妊娠中期存在促炎优势,而在有>2 次妊娠丢失的情况下,抗炎环境更为正常。由于无菌和感染相关炎症在妊娠丢失中都有作用,因此招募有良好和不良妊娠结局的女性的研究可能会揭示本研究对制定更好的管理/治疗策略的重要性。

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