Clinical medical school, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Gynecology Department, Hospital of Chengdu University of TCM, Chengdu, China.
Am J Reprod Immunol. 2023 Dec;90(6):e13792. doi: 10.1111/aji.13792.
The immune system plays an essential role in embryonic implantation and pregnancy, but the molecular details remain controversial. In the past four decades, human leukocyte antigen (HLA)-G and -F have garnered significant attention.
MEDLINE, EMBASE, Web of Science, and the Cochrane Trials Registry were searched from their inception dates until December 2022. Studies were selected following PRISMA guidelines. Meta-analyses were used to assess the relationship of soluble HLA-G (sHLA-G) and HLA-G 3'-untranslated region polymorphisms with recurrent miscarriage (RM) and recurrent implantation failure (RIF). Narrative synthesis was conducted to determine the association of RM with other single nucleotide polymorphisms (SNPs) and HLA-G protein in tissues and of RIF with HLA-F. Risk-of-bias was assessed using ROBINS-I. Publication bias was assessed using Egger's and Begg's tests.
Finally, 42 articles were eligible for inclusion in the systematic review (32 in the meta-analysis; 13 in narrative synthesis). We found a significant association between the 14-bp ins/del HLA-G polymorphism and RM risk, but no definitive association with RIF risk. Women with RM had lower blood concentrations of sHLA-G during pregnancy and non-pregnancy than did controls. For women in the RIF group, no significant difference was found.
HLA-G protein and gene expression levels may be closely related to RM. The relevance of HLA-G to RIF is still being determined. A narrative synthesis of current studies has shown that HLA-F is likely associated with RIF.
免疫系统在胚胎着床和妊娠中起着至关重要的作用,但分子细节仍存在争议。在过去的四十年中,人类白细胞抗原(HLA)-G 和 -F 引起了广泛关注。
从其创建日期到 2022 年 12 月,我们在 MEDLINE、EMBASE、Web of Science 和 Cochrane 临床试验注册中心进行了搜索。根据 PRISMA 指南选择研究。我们使用荟萃分析来评估可溶性 HLA-G(sHLA-G)和 HLA-G 3'-非翻译区多态性与复发性流产(RM)和复发性着床失败(RIF)的关系。我们进行了叙述性综合分析,以确定 RM 与其他单核苷酸多态性(SNPs)和组织中的 HLA-G 蛋白的关系,以及 RIF 与 HLA-F 的关系。使用 ROBINS-I 评估风险偏差。使用 Egger 和 Begg 检验评估发表偏倚。
最终,有 42 篇文章符合系统评价的纳入标准(32 篇进行荟萃分析;13 篇进行叙述性综合分析)。我们发现 14-bp ins/del HLA-G 多态性与 RM 风险之间存在显著关联,但与 RIF 风险无明确关联。RM 患者在妊娠和非妊娠期间的血液 sHLA-G 浓度低于对照组。对于 RIF 组的女性,未发现显著差异。
HLA-G 蛋白和基因表达水平可能与 RM 密切相关。HLA-G 与 RIF 的相关性仍在确定中。对当前研究的叙述性综合分析表明,HLA-F 可能与 RIF 相关。