School of Sciences (Zoology), Maulana Azad National Urdu University, Gachibowli, Hyderabad, Telangana, India.
Department of Biochemistry, Osmania University, Hyderabad, Telangana, India.
Am J Reprod Immunol. 2023 Dec;90(6):e13798. doi: 10.1111/aji.13798.
Recurrent Pregnancy Loss (RPL) is a disorder characterized by two or more pregnancy losses within 20th week of gestation. Globally 1-5% of the couples are affected, 50% of these cases are with unknown etiology. HLA-G, an Immuno-modulatory molecule is a non-classical MHC-1 protein, expressed abundantly on extravillous trophoblastic cells, responsible for spiral artery remodeling, maintaining maternal immune tolerance and fetal growth by adjusting pro and anti-inflammatory milieu during different gestational phases.
In the present case-control study CD4+HLA-G+ tTreg cells were enumerated by flow cytometry and estimation of the circulating levels of sHLA-G in the blood samples of 300 mid-gestation pregnant women with (iRPL) and without history of RPL (nRPL) by Enzyme-linked Immunosorbent assay was done. The cases included 92 primary and 58 secondary RPL cases RESULTS: A significant reduction in number of tTregs and elevated levels of circulating sHLA-G in iRPL (.03, 200.9) versus nRPL (.09, 90.32) was observed. Further, the primary cases showed higher circulating sHLA-G and no difference in relation to CD4+HLA-G+ tTregs compared to the secondary cases. Receiver operating curve (ROC) characteristics of sHLA-G (AUC = .8) was superior to CD4+HLA-G+ (AUC = .7) for iRPL patients over nRPL group.
Our results are suggestive of the over-expression of sHLA-G which may be caused due to its shedding from surface of trophoblast as a compensatory mechanism to save the on-going pregnancy. To realize the present outcome, studies are required on on-going pregnancy follow-up cases with favorable and unfavorable pregnancy outcome.
复发性流产（RPL）是一种以妊娠 20 周内发生两次或两次以上流产为特征的疾病。全球有 1-5%的夫妇受到影响，其中 50%的病例病因不明。HLA-G 是一种免疫调节分子，是一种非经典 MHC-1 蛋白，在绒毛外滋养细胞中大量表达，负责螺旋动脉重塑，通过在不同妊娠阶段调节促炎和抗炎环境，维持母体免疫耐受和胎儿生长。
在本病例对照研究中，通过流式细胞术计数 CD4+HLA-G+tTreg 细胞，并通过酶联免疫吸附试验检测 300 名中期妊娠孕妇（iRPL，有流产史）和无流产史孕妇（nRPL）血液样本中 sHLA-G 的循环水平。病例包括 92 例原发性和 58 例继发性 RPL 病例。
与 nRPL（0.09，90.32）相比，iRPL（0.03，200.9）中 tTreg 细胞数量减少，循环 sHLA-G 水平升高。此外，与继发性病例相比，原发性病例的循环 sHLA-G 水平较高，而与 CD4+HLA-G+tTreg 细胞无差异。sHLA-G 的受试者工作特征曲线（ROC）特征（AUC=0.8）优于 CD4+HLA-G+tTregs（AUC=0.7），可用于鉴别 iRPL 患者与 nRPL 组。
我们的结果提示 sHLA-G 过度表达，可能是由于其从滋养细胞表面脱落作为一种代偿机制来挽救正在进行的妊娠。为了实现目前的结果，需要对有良好和不良妊娠结局的正在进行的妊娠随访病例进行研究。
