Abnormal expression of the costimulatory molecule B7‐H4 in placental chorionic villous and decidual basalis tissues of patients with preeclampsia and HELLP syndrome

Background B7‐H4, a checkpoint molecule of the B7 family, regulates a broad spectrum such as T‐cell activation, cytokine secretion, tumour progression, and invasion capacities. Our previous data revealed that soluble B7‐H4 (sB7‐H4) blood serum levels are elevated in women at high risk for the hypertensive pregnancy disorder preeclampsia (PE) in the first trimester, as well as in patients with confirmed early/late‐onset PE. Aim We here aim to investigate the expression pattern of B7‐H4 in placental tissues of PE and HELLP Syndrome versus control group. Methods B7‐H4 protein expression and localization were investigated by immunoblotting and co‐immunohistochemistry in placental chorionic villous and decidual basalis tissues. Results B7‐H4 protein was prominently expressed at the cell membrane, in the cytoplasm of the syncytiotrophoblast (STB) and interstitial extravillous trophoblast (EVT). B7‐H4 protein levels in placental chorionic villous tissue were significantly higher in women with early‐onset/late‐onset PE and HELLP, while it was decreased in decidual basalis tissues of early‐onset PE and HELLP compared with controls. Conclusion B7‐H4 was inversely expressed in placental chorionic villous and decidual basalis tissues of PE and HELLP patients. The increase in B7‐H4 in the STB in PE and HELLP may lead to excessive apical expression and release of soluble B7‐H4 in the maternal circulation. In contrast, the decrease in B7‐H4 in decidual basalis tissues could be related to the decrease in invasion ability of the EVT in PE. Thus, the current results strongly suggest that B7‐H4 is involved in the pathogenesis of PE and HELLP.