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Published on: January 26, 2024
Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia
Catalina M Valencia1, Alyssa R Hersh2, Richard M Burwick3
1Clínica Reina Sofía Colsanitas SA, Bogotá, Distrito Capital de Bogotá, Colombia; Fundared-Materna, Bogotá, Distrito Capital de Bogotá, Colombia; Universidad CES, Medellín, Antioquia, Colombia.
Insights
Low plasma C5b-9 and high urine C5b-9 levels indicate end-organ injury in preeclampsia. This finding may help identify complement-mediated injury in patients with preeclampsia.
Area of Science:
- Obstetrics and Gynecology
- Immunology
- Nephrology
Background:
- Preeclampsia is a hypertensive disorder of pregnancy.
- End-organ injury is a serious complication of preeclampsia.
- The terminal complement complex, C5b-9, plays a role in inflammatory processes.
Purpose of the Study:
- To investigate the correlation between soluble C5b-9 levels and end-organ injury in preeclampsia.
- To determine if C5b-9 can serve as a biomarker for complement-mediated end-organ injury.
Main Methods:
- A multi-center observational study (Project COPA) enrolled 298 hypertensive pregnant women.
- Participants were categorized into four groups: chronic hypertension, gestational hypertension, preeclampsia, and severe preeclampsia.
- Plasma and urine C5b-9 concentrations were measured using enzyme-linked immunosorbent assays (ELISAs).
- End-organ injury was defined by specific clinical criteria for serum creatinine, liver enzymes, platelet count, and lactate dehydrogenase.
Main Results:
- Low plasma C5b-9 levels (Q1) were associated with a higher incidence of end-organ injury, including low platelet count and elevated serum creatinine.
- High urinary C5b-9 levels (Q4) were also linked to increased end-organ injury, specifically low platelet count and elevated serum creatinine.
- Statistical significance (P < 0.05) was observed for these associations.
Conclusions:
- A distinct pattern of increased urine and decreased plasma C5b-9 levels was identified in preeclampsia patients with end-organ injury.
- Soluble C5b-9 levels show potential as biomarkers for identifying complement-mediated end-organ injury in preeclampsia.
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.
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