The immunological role of B7‐H4 in pregnant women with Sars‐Cov2 infection

PROBLEM: T‐cells are key players in fighting the coronavirus disease 2019 (COVID‐19). The checkpoint molecule B7‐H4, a member of the B7 family, can inhibit T‐cell activation and proliferation by inhibiting NF‐kb expression. We aimed to elucidate the immunological role of soluble B7‐H4 (sB7‐H4) and B7‐H4 in pregnant women suffered from an acute Sars‐Cov2 infection. METHODS: Expression levels of sB7‐H4 and cytokines were detected by enzyme linked immunosorbent assay. B7‐H4 and cytokines mRNA expression was analyzed by qPCR, and B7‐H4 and NF‐κb (p65) protein levels were investigated by western blot and immunofluorescence staining in placenta chorionic villous and decidual basalis tissues of COVID‐19 affected women and healthy controls. RESULTS: Fibrinoid necrosis in the periphery of placental villi was increased in the COVID‐19‐affected patients. sB7‐H4 protein in maternal and cord blood serum and IL‐6/IL‐10 were increased while leukocytes were decreased during SARS‐CoV‐2 infection. Serum sB7‐H4 level was increased according to the severity of SARS‐Cov‐2 infection. Cytokines (IL‐6, IL‐18, IL‐1β, TNF‐α), B7‐H4 mRNA and protein in the decidual basalis tissues of COVID‐19‐infected pregnant women were significantly increased compared to healthy controls. IL‐18 and IL‐1β were significantly increased in the placenta chorionic villous samples of COVID‐19 affected patients, while NF‐κb (p65) expression was decreased. CONCLUSIONS: The expression of the immunological marker sB7‐H4 correlated with the severity of COVID‐19 disease in pregnant women. sB7‐H4 and B7‐H4 can be used to monitor the progression of COVID‐19 infection during pregnancy, and for evaluating of the maternal immune status.