title: 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 (AT(1)-AA). However, the prevalence of AT(1)-AA in PE remains unknown, and the correlation of AT(1)-AA titers with the severity of the disease remains undetermined. We used a sensitive and high-throughput luciferase bioassay to detect AT(1)-AA levels in the serum of 30 normal, 37 preeclamptic (10 mild and 27 severe), and 23 gestational hypertensive individuals. Here we report that AT(1)-AA is highly prevalent in PE ( approximately 95%). Next, by comparing the levels of AT(1)-AA among women with mild and severe PE, we found that the titer of AT(1)-AA is proportional to the severity of the disease. Intriguingly, among severe preeclamptic patients, we discovered that the titer of AT(1)-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 AT(1)-AA, and not soluble fms-like tyrosine kinase-1, levels are elevated in gestational hypertensive patients. These data serve as compelling clinical evidence that AT(1)-AA is highly prevalent in PE, and its titer is strongly correlated to the severity of the disease.
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, Tex, USA.
authors.forename: Athar H
authors.initials: AH
authors.lastname: Siddiqui
authors.forename: Roxanna A
authors.initials: RA
authors.lastname: Irani
authors.forename: Sean C
authors.initials: SC
authors.lastname: Blackwell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ramin
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Kellems
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000276:immunology / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy; D011336:Probability; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood / Q000276:immunology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014162:Transfection; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1