Low expression of soluble human leukocyte antigen G in early gestation and subsequent placenta-mediated complications of pregnancy

Aim: Abnormal placentation is a common pathogenic mechanism of many placenta-mediated complications of late pregnancy, including pre-eclampsia, fetal growth restriction, stillbirth, and placental abruption. During successful placentation, the trophoblast (which is a semi-allograft) is not rejected by decidual immune cells because of maternal immune tolerance, mainly induced by human leukocyte antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the development of complications of pregnancy. The aim of this study was to determine whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of pregnancy may be associated with subsequent placenta-mediated complications. Methods: For this retrospective case-control study, 117 cases of placenta-mediated complications of pregnancy and 234 controls with uneventful pregnancy were selected. Plasma sHLA-G levels were measured at 11-13weeks' gestation by the enzyme-linked immunosorbent assay method in blood samples previously obtained at first-trimester prenatal screening for chromosomal fetal abnormalities. Results: Women who subsequently developed placenta-mediated complications had significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08IU/mL) than controls (median, 49.10IU/mL; P=0.008). An sHLA-G level lower than 43.50IU/mL at the end of the first trimester was associated with a twofold increased risk of developing a pregnancy complication (odds ratio, 1.82; 95% confidence interval, 1.22-2.73). The strongest association, although only moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95% confidence interval, 1.08-6.56). Conclusion: Placenta-mediated complications of pregnancy may be associated with low sHLA-G levels in the first trimester, suggesting a potential role of sHLA-G in the early stages of placentation.