ORIGINAL ARTICLE: Soluble Human Leukocyte Antigen‐G Isoforms in Maternal Plasma in Early and Late Pregnancy

Abstract

Problem Human Leukocyte Antigen (HLA)‐G is a class Ib gene located in the human major histocompatibility complex (MHC). Several lines of investigation indicate that the HLA‐G molecule is involved in the maternal acceptance of the semi‐allogenic fetus during pregnancy and in the development of tolerance. Expression of soluble HLA‐G (sHLA‐G) is positively correlated with successful in vitro fertilization (IVF) treatments, and aberrant expression of HLA‐G in certain complications of pregnancy, such as pre‐eclampsia and spontaneous abortion, has been reported. The main purpose of this study was to investigate the levels of different soluble HLA‐G isoforms in maternal plasma in early and late pregnancy.Method of study Soluble HLA‐G (sHLA‐G) can be detected in maternal blood, and in this study, two different isoforms of sHLA‐G, namely sHLA‐G1 generated by shedding of membrane‐bound HLA‐G1 and HLA‐G generated by specific HLA‐G transcripts, have been investigated early [median of 16.4 weeks of gestation (GW)] and late (median: 38.9 GW) in pregnancy in an original cohort of 580 pregnant Caucasian women.Results Lower concentrations of sHLA‐G1 were found late in pregnancy (>32 GW) in a group of women with severe pre‐eclampsia compared with controls with uncomplicated pregnancies (P = 0.029, PC = 0.09; Mann–Whitney; Logistic regression analysis: P = 0.024, OR = 0.920, 95% CI: 0.855–0.989). However, this was not the case with HLA‐G5, and significantly more of the cases with severe pre‐eclampsia had detectable plasma HLA‐G5 compared with that of the control group (P = 0.013, PC = 0.04; Mann–Whitney). Similar findings were not observed in women with gestational hypertension or existing hypertension continuing into pregnancy. Furthermore, there was a trend toward lower maternal plasma sHLA‐G1 in a group of women with premature birth (<37 GW) compared with that of the control group (P = 0.028, PC = 0.17; Mann–Whitney). On the contrary, HLA‐G5 was lower in the control group compared with that in the premature group (P = 0.004, PC = 0.02; Mann–Whitney).Conclusion This study shows in line with other published studies that a high, detectable soluble HLA‐G concentration in maternal plasma or serum is not mandatory for a successful pregnancy. However, complications during pregnancy, such as (severe) pre‐eclampsia, spontaneous abortion, IUGR, and premature birth, are associated with a low or undetectable level of soluble HLA‐G in the maternal blood circulation. Also, this study indicates that sHLA‐G1 is the interesting soluble HLA‐G isoform in pre‐eclampsia, and that low or undetectable levels of HLA‐G5 at the end of pregnancy seem to be associated with an uncomplicated normal pregnancy, whereas in severe pre‐eclampsia and possibly other pregnancy complications, such as preterm birth and IUGR, the level of HLA‐G5 is higher.