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Abstract: TH-PO751

Preeclampsia Is Associated With Complement Activation in Maternal and Fetal Circulation and Placental Tissue

Session Information

Category: Women's Health and Kidney Diseases

  • 2100 Women's Health and Kidney Diseases

Authors

  • Blakey, Hannah, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
  • Sarween, Nadia, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
  • Wong, Edwin Kwan Soon, Newcastle University, Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
  • Sheerin, Neil S., Newcastle University, Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
  • Bramham, Kate, King's College London, London, London, United Kingdom
  • Harris, Claire L., Newcastle University, Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
  • Knox, Ellen, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, Birmingham, United Kingdom
  • Drayson, Mark Trehane, University of Birmingham, Birmingham, Birmingham, United Kingdom
  • Lipkin, Graham, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
Background

Pre-eclampsia (PE) is a leading cause of obstetric morbidity. There remains no definitive therapy other than delivery. Long-term sequelae include an increased lifetime risk of chronic kidney disease. Complement dysregulation has been implicated in the pathogenesis of PE, although the current evidence base is limited. Our aim was to compare patterns of placental and maternal and fetal circulatory complement activity in healthy pregnant women and those with PE, to gain insight into complement activation and guide potential complement-modifying therapies.

Methods

Women with PE and healthy pregnant controls were recruited from a tertiary obstetric centre. Samples of maternal and umbilical cord blood were tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue stained for C3d, C4d, C9 and C1q, from women with PE (n=34) and healthy pregnant controls (n=33). Properdin and Ba concentrations were validated in maternal plasma samples (PE n=35; controls n=35) from a separate tertiary centre cohort.

Results

Women with PE had significantly lower blood 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. Properdin findings were replicated in the validation cohort (mean 5282 in PE vs 7021 ng/ml in controls, p<0.001). Combined cohort average properdin concentrations were 1945 ng/ml lower in PE vs controls (p<0.001), AUROC 0.87. Umbilical cord Ba was higher in PE vs controls (mean 380.7 vs 210.5 ng/ml, p=0.015). There was increased placental C4d deposition at the syncytiotrophoblast membrane in PE vs controls (median immunoreactivity score 3 vs 0, p<0.001). Maternal plasma properdin and C4 were strongly negatively correlated with placental C4d deposition.

Conclusion

Our data confirm excessive complement activation products in maternal and fetal circulation, strongly associated with placental complement deposition in women with PE. Classical or lectin pathway activity drives placental C4d deposition, which is amplified by the alterative pathway amplification loop, leading to significant changes in plasma complement biomarkers. Inhibition of complement activation is a potential therapeutic target in the treatment of PE.