Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: Correlation with disease severity

Abstract

Preeclampsia (PE), a syndrome affecting 5% of pregnancies, characterized by hypertension and proteinuria, is a leading cause of maternal and fetal morbidity and mortality. The condition is often accompanied by the presence of a circulating maternal autoantibody, the angiotensin II type I receptor agonistic autoantibody (AT1-AA). However, the prevalence of AT1-AA in PE remains unknown, and the correlation of AT1-AA titers with the severity of the disease remains undetermined. We used a sensitive and high-throughput luciferase bioassay to detect AT1-AA levels in the serum of 30 normal, 37 preeclamptic (10 mild and 27 severe), and 23 gestational hypertensive individuals. Here we report that AT1-AA is highly prevalent in PE (95%). Next, by comparing the levels of AT1-AA among women with mild and severe PE, we found that the titer of AT1-AA is proportional to the severity of the disease. Intriguingly, among severe preeclamptic patients, we discovered that the titer of AT1-AA is significantly correlated with the clinical features of PE: systolic blood pressure (r=0.56), proteinuria (r=0.70), and soluble fms-like tyrosine kinase-1 level (r=0.71), respectively. Notably, only AT1-AA, and not soluble fms-like tyrosine kinase-1, levels are elevated in gestational hypertensive patients. These data serve as compelling clinical evidence that AT1-AA is highly prevalent in PE, and its titer is strongly correlated to the severity of the disease. © 2010 American Heart Association. All rights reserved.