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

Abstract

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.

Is it possible to identify COVID-19 infection-related biomarkers during pregnancy?: A prospective study in Turkish population

“…Coronavirus disease 2019 (COVID- 19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, was first discovered in Wuhan, China, in December 2019. [1] The disease escalated into a local public health concern and was officially declared a pandemic by the World Health Organization on March 11, 2020.…”

“…[16] B7 family refers to a group of glycoproteins that function as co-signaling molecules, inducing effective immune responses and preventing unwanted autoimmunity. [19] B7 homolog 4 (B7H4), a coinhibitory member of the B7 family, modulates the activity of T cells and serves as a T-cell-negative regulator that suppresses host immunity and allows tumor cells to evade immunological surveillance. [19][20][21] Given that its level increases during inflammatory events, B7H4 may be used as a biomarker to predict toxemia during pregnancy.…”

“…[19] B7 homolog 4 (B7H4), a coinhibitory member of the B7 family, modulates the activity of T cells and serves as a T-cell-negative regulator that suppresses host immunity and allows tumor cells to evade immunological surveillance. [19][20][21] Given that its level increases during inflammatory events, B7H4 may be used as a biomarker to predict toxemia during pregnancy. In fact, a significant correlation between B7H4 levels and the severity of COVID-19 was reported in pregnant women.…”

“…In fact, a significant correlation between B7H4 levels and the severity of COVID-19 was reported in pregnant women. [19] Pregnancy-related immunization primarily involves the immune system's cellular functions. Anti-inflammatory and pro-inflammatory cytokine levels in the maternal serum should be comprehensively regulated throughout pregnancy.…”

“…In fact, a significant correlation between B7H4 levels and the severity of COVID-19 was reported in pregnant women. [ 19 ]…”