Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients

Int J Mol Sci. 2024 Oct 15;25(20):11082. doi: 10.3390/ijms252011082.

Abstract

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2-28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5-30 weeks), and gestational age-matched controls (N = 8, 22 + 4-31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases.

Keywords: B7-H4; placental dysfunction; preeclampsia; preeclampsia therapy; preterm birth; soluble Endoglin; soluble fms-like tyrosine kinase 1; therapeutic plasma exchange.

MeSH terms

  • Adult
  • Biomarkers* / blood
  • Endoglin / blood
  • Endoglin / metabolism
  • Female
  • Humans
  • Placenta* / metabolism
  • Plasma Exchange* / methods
  • Pre-Eclampsia* / blood
  • Pre-Eclampsia* / metabolism
  • Pre-Eclampsia* / therapy
  • Pregnancy
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1* / blood
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1* / metabolism
  • Vascular Endothelial Growth Factor Receptor-1* / blood
  • Vascular Endothelial Growth Factor Receptor-1* / metabolism

Substances

  • Biomarkers
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • FLT1 protein, human
  • Endoglin
  • Tumor Necrosis Factor-alpha