Soluble B7-H4 Blood Serum Levels Are Elevated In Women At High Risk For Preeclampsia In The First Trimester, As Well As In Patients With Confirmed Preeclampsia

ProblemB7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta.Method of studyMaternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13weeks' gestation with elevated risk for PE (n=48) and women without elevated risk for PE (n=47). In the third trimester, sB7-H4 serum levels (n=166) and B7-H4 mRNA expression in the placenta (n=54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls.ResultsIn the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P<.0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P=.01 and P=.006, respectively) and late-onset PE (P=.03 and P=.004, respectively) compared to healthy controls, but not compared to FGR.ConclusionsB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE.