Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada; Department of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR.
Am J Obstet Gynecol. 2022 Oct;227(4):641.e1-641.e13. doi: 10.1016/j.ajog.2022.07.021. Epub 2022 Jul 19.
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.
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.
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.
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.
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.
滋养层细胞外表达每一个非经典主要组织相容性复合体 I 类抗原 - 人类白细胞抗原 E、F 和 G-以及一个单一的经典 I 类抗原，人类白细胞抗原 C。我们最近证明了人类白细胞抗原 C、G 和 F 在早期滋养层细胞外侵袭和胎盘形成过程中的动态表达模式。
本研究旨在验证这样一种假设，即妊娠免疫炎症介导的并发症，如早发性子痫前期和早产，可能表现出非经典人类白细胞抗原的改变表达谱。
对来自足月非分娩、早产和严重早发性子痫前期的胎盘绒毛组织和基底板切片进行实时定量聚合酶链反应、western blot 和免疫组织化学检测，这些样本既有伴有小于胎龄儿的，也有不伴有小于胎龄儿的。
人类白细胞抗原 G 强烈且仅由胎盘基底板内的滋养层细胞外表达，其水平在伴有小于胎龄儿的严重早发性子痫前期妊娠中增加，与健康足月对照组相比。人类白细胞抗原 C 在子痫前期妊娠的滋养层细胞外表现出类似的特征，但在绒毛胎盘中的表达显著下降。与足月和早产分娩相比，严重早发性子痫前期妊娠的滋养层细胞外和绒毛胎盘中的人类白细胞抗原 F 蛋白水平均降低，无论是否伴有小于胎龄儿。人类白细胞抗原 E 在子痫前期胎盘的血管中减少，与足月和早产分娩相比。与特发性早产相比，伴有绒毛膜羊膜炎的早产病例中胎盘的人类白细胞抗原 F 和 C 水平升高。
母体-胎儿界面上胎盘人类白细胞抗原表达的失调可能导致伴有绒毛膜羊膜炎的早产和与严重早发性子痫前期相关的过度母体全身炎症导致的母体耐受性受损。
