Early Prediction of Preeclampsia by Using Serum Human Leukocyte Antigen G: A Retrospective Case-Control Study Followed by a Prospective Unselected Cohort Study

Abstract

Background: Human leukocyte antigen G (HLA-G), a non-classic class I antigen, has been well documented in that its concentrations in maternal peripheral blood are significantly lower in pregnant women with preeclampsia (PE) than those pregnant women without PE. However, the clinical significance of measuring serum HLA-G as a test for predicting PE development has not been studied. Methods: First, we determined cutoff values for serum HLA-G levels for PE in a retrospective case-control study with 100 PE patients and 300 non-PE pregnant women. Then, we performed a prospective unselected cohort study with 3,439 pregnant women. In the prospective study, pregnant women whose serum HLA-G levels were lower than the cutoff values and who had other PE risk factors were included in a PE rule-in group. In contrast, pregnant women whose serum HLA-G levels were greater than the cutoff values and who had no other PE risk factors were included in a PE rule-out group. The participants were followed up until end of study. Finding: The cutoff values of serum HLA-G levels for PE were established in the retrospective study. In the subsequent prospective study, we demonstrated that serum HLA-G levels lower than 80 U/mL at 10−13 gestational weeks (GW) in the PE rule-in group showed a positive predictive value for PE development with 83.78% sensitivity and 87.93% specificity while serum HLA-G levels higher than 80 U/mL at 10−13 GW in the PE rule-out group had a negative predictive value with 88.57% sensitivity and 97.14% specificity. Interpretation: Serum HLA-G levels lower than 80 U/mL in the first trimester of pregnancy can be used to predict the absence or presence of PE development in the third trimester of pregnancy. Funding Statement: Allowance to SMY for new technique development from provincial and municipal government department of Sichuan, Chengdu, P. R. China. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The hospital review board (Second Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China) approved the study protocol. All participants provided their written informed consent.