Human leukocyte antigen HLA-C, HLA-G, HLA-F, and HLA-E placental profiles are altered in early severe preeclampsia and preterm birth with chorioamnionitis

Background: The extravillous trophoblast expresses each of the nonclassical major histocompatibility complex class I antigens—human leukocyte antigens E, F, and G—and a single classical class I antigen, human leukocyte antigen C. We recently demonstrated dynamic expression patterns of human leukocyte antigens C, G, and F during early extravillous trophoblast invasion and placentation. Objective: This study aimed to investigate the hypothesis that the immune inflammatory mediated complications of pregnancy such as early preeclampsia and preterm labor may show altered expression profiles of nonclassical human leukocyte antigens. Study Design: Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were performed on placental villous tissues and basal plate sections from term nonlaboring deliveries, preterm deliveries, and severe early-onset preeclampsia, both with and without small-for-gestational-age neonates. Results: Human leukocyte antigen G is strongly and exclusively expressed by the extravillous trophoblast within the placental basal plate, and its levels increase in pregnancies complicated by severe early-onset preeclampsia with small-for-gestational-age neonates relative to those of healthy term controls. Human leukocyte antigen C shows a similar profile in the extravillous trophoblast of preeclamptic pregnancies, but significantly decreases in the villous placenta. Human leukocyte antigen F protein levels are decreased in both extravillous trophoblast and villous placenta of severe early-onset preeclamptic pregnancies, both with and without small-for-gestational-age neonates, compared with those found in term and preterm birth deliveries. Human leukocyte antigen E decreases in blood vessels in placentas from preeclamptic pregnancies relative to its levels in term and preterm birth deliveries. Placental levels of human leukocyte antigens F and C are increased in cases of preterm birth with chorioamnionitis relative to those of cases of idiopathic preterm birth. Conclusion: Dysregulation of placental human leukocyte antigen expression at the maternal–fetal interface may contribute to compromised maternal tolerance in preterm birth with chorioamnionitis and excessive maternal systemic inflammation associated with severe early-onset preeclampsia.