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

Abstract

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.

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

“…2021. 27 B7‐H4 was strongly expressed in the decidua basalis tissues of COVID‐19 placenta (Figure 5H ). However, only few cells revealed a strong B7‐H4 expression in control placentas (Figure 5G ).…”

“…For specific experimental steps, please refer to our published article. 27 To sum up, for incubation overnight at 4°C the primary antibodies polyclonal rabbit anti‐B7‐H4 (R&D Systems, #2318A; 1:1000) and purified polyclonal rabbit anti‐NF‐kb (Santa Cruz, sc‐372; 1:250) and for 1 h at room temperature the primary antibody mouse monoclonal‐β‐Actin Peroxidase (Sigma A3845; 1:200.000) for normalization purposes. The secondary antibody (goat anti‐rabbit IgG [H+L], G21234; 1:7500) was used for detecting B7‐H4 and NF‐kb 1 h at room temperature.…”

“…2021). 27 The primary antibodies polyclonal rabbit anti‐B7‐H4 (R&D Systems, #2318A; 1:30), purified polyclonal rabbit anti‐NF‐kb (Santa Cruz, sc‐372; 1:25) were used overnight at 4°C. After that the following secondary antibody was applied: anti‐rabbit Alexa Fluor 488 (Life Technologies, A10521; 1:200) and incubated for 1 h at room temperature.…”

“… 26 We also found that B7‐H4 was detected on both the STB and EVT. 27 Neither the origin nor the function of sB7‐H4 is fully understood. However, it is known that sB7‐H4 was secreted when cells were under inflammatory conditions.…”

Placental Syndromes—A New Paradigm in Perinatology

“…B7-H4, a checkpoint molecule of the B7 family, regulates T-cell activation and cytokine secretion. It was found to be decreased in the decidual basalis tissues of early-onset PE and HELLP, suggesting that B7-H4 is involved in the pathogenesis of both disorders [ 68 ]. Therefore, HELLP is considered as a placental syndrome.…”