RESUMO
OBJECTIVES: Pre-eclampsia (PE) is a leading cause of obstetric morbidity, with no definitive therapy other than delivery. We aimed to compare complement markers in maternal and fetal circulation, and placental tissue, between women with PE and healthy pregnant controls. STUDY DESIGN: Maternal and umbilical cord blood was tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue for C3d, C4d, C9 and C1q, from women with PE (nâ¯=â¯34) and healthy pregnant controls (nâ¯=â¯33). Maternal properdin and Ba tests were repeated in a separate validation cohort (PE nâ¯=â¯35; healthy pregnant controls nâ¯=â¯35). MAIN OUTCOME MEASURES: Complement concentrations in maternal and umbilical cord blood, and placental immunohistochemical complement deposition. RESULTS: Women with PE had significantly lower concentrations of properdin (mean: 4828 vs 6877â¯ng/ml, pâ¯<â¯0.001) and C4 (mean: 0.20 vs 0.31â¯g/l, pâ¯<â¯0.001), and higher Ba (median: 150 vs 113â¯ng/ml, pâ¯=â¯0.012), compared to controls. After controlling for gestational age at blood draw, average properdin concentration was 1945â¯ng/ml lower in PE vs controls (95â¯% CI: 1487-2402, pâ¯<â¯0.001). Of the cord blood markers assessed, only Ba differed significantly between PE and controls (median: 337 vs 233â¯ng/ml, pâ¯=â¯0.004). C4d staining of the syncytiotrophoblast membrane was increased in PE vs controls (median immunoreactivity score 3 vs 0, pâ¯<â¯0.001). Maternal properdin and C4 were significantly negatively correlated with placental C4d staining. CONCLUSIONS: Our data confirm excessive placental complement deposition associated with significant concurrent changes in maternal and fetal circulating complement biomarkers in PE. Inhibition of complement activation is a potential therapeutic target.