Maternal and fetal HLA heterozygosity in preeclampsia: Insights from a large multi-ancestry pregnancy cohort

Preeclampsia is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface contributing to its development. The study included 12,790 women (4,770 with preeclampsia and 8,020 without) from diverse ethnic backgrounds and examined the relationship between HLA heterozygosity and preeclampsia risk. Heterozygosity in HLA class I loci had a protective effect in preterm preeclampsia (OR=0.82), while fetal heterozygosity at HLA-DQB1 was associated with increased preeclampsia risk (OR=1.36) and preterm preeclampsia risk (OR=1.73). Maternal-fetal mismatch analysis revealed specific associations with preterm preeclampsia, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. The findings highlight distinct immunogenetic contributions from both mother and fetus to preeclampsia risk.