UP‐regulated levels of sHLA‐G in women with a history of RPL in mid‐gestation presumably to achieve ongoing pregnancy

Abstract

ProblemRecurrent 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.Method of studyIn 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 casesResultsA 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. Conclusions: 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.