Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia

Pregnancy Hypertens. 2022 Aug:29:92-97. doi: 10.1016/j.preghy.2022.07.001. Epub 2022 Jul 6.

Abstract

Objective: We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia.

Study design: Project COPA (Complement and Preeclampsia in the Americas), a multi-center observational study in Colombia from 2015 to 2016, enrolled hypertensive pregnant women into four groups: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features. Trained coordinators collected clinical data, blood and urine. End-organ injury was defined by serum creatinine ≥ 1.0 mg/dl, aspartate transaminase ≥ 70U/L, platelet count < 150,000/µl, or lactate dehydrogenase ≥ 500 U/L. Data were analyzed by χ2 or Fisher's exact test with significance at P < 0.05.

Main outcome measure: C5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays.

Results: In total, 298 hypertensive participants were enrolled. Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 concentration. Participants with low plasma C5b-9 levels (Q1) were more likely to have end-organ injury compared to those with higher levels (Q2-Q4) [platelet count < 150,000/μl (20.8% vs. 8.4%, P = 0.01); elevated serum creatinine ≥ 1.0 mg/dl (14.9% vs. 4.5%, P = 0.009)]. In contrast, participants with high urinary C5b-9 levels (Q4) were more likely to have end-organ injury compared to those with lower levels (Q1-Q3) [platelet count < 150,000/μl (19.7% vs. 7.4%, P = 0.003); elevated serum creatinine ≥ 1.0 mg/dl (12.3% vs. 4.4%, P = 0.025)].

Conclusion: We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury. Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia.

Keywords: Complement membrane attack complex; Complement system proteins; Hypertension; Preeclampsia; Pregnancy.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Complement Membrane Attack Complex / urine
  • Complement System Proteins
  • Creatinine
  • Female
  • Humans
  • Hypertension* / urine
  • Pre-Eclampsia*
  • Pregnancy

Substances

  • Complement Membrane Attack Complex
  • Complement System Proteins
  • Creatinine