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Pre-eclampsia is associated with complement pathway activation in the maternal and fetal circulation, and placental tissue

Lookup NU author(s): Dr Ruyue Sun, Dr Long Xie, Rebecca Russell, Dr Edwin Wong, Professor Neil SheerinORCiD, Professor Claire Harris

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Abstract

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, in 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 (n=34) and healthy pregnant controls (n=33). Maternal properdin and Ba tests were repeated in a separate validation cohort (PE n=35; healthy pregnant controls n=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. 6877 ng/ml, p<0.001) and C4 (mean: 0.20 vs. 0.31 g/l, p<0.001), and higher Ba (median: 150 vs. 113 ng/ml, p=0.012), compared to controls. After controlling for gestational age at blood draw, average properdin concentration was 1945 ng/ml lower in PE vs. controls (95% CI: 1487-2402, p<0.001). Of the cord blood markers assessed, only Ba differed significantly between PE and controls (median: 337 vs. 233 ng/ml, p=0.004). C4d staining of the syncytiotrophoblast membrane was increased in PE vs. controls (median immunoreactivity score 3 vs. 0, p<0.001). Maternal blood properdin and C4 were significantly negatively correlated with placental C4d staining. Conclusions: Our data confirm excessive complement activation in maternal and fetal circulation in women with PE, associated with placental complement deposition. Inhibition of complement activation is a potential therapeutic target.

Publication metadata

Author(s): Blakey H, Sun R, Xie L, Russell R, Sarween N, Hodson J, Hargitai B, Marton T, Neil DAH, Wong E, Sheerin NS, Bramham K, Harris CL, Knox E, Drayson M, Lipkin G

Publication type: Article

Publication status: Published

Journal: Pregnancy Hypertension

Year: 2023

Volume: 32

Pages: 43-49

Print publication date: 01/06/2023

Online publication date: 21/04/2023

Acceptance date: 11/04/2023

Date deposited: 11/04/2023

ISSN (print): 2210-7789

ISSN (electronic): 2210-7797

Publisher: Elseiver

URL: https://doi.org/10.1016/j.preghy.2023.04.001

DOI: 10.1016/j.preghy.2023.04.001

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