Prevalence of Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor and Soluble fms-Like Tyrosine Kinase 1 in a Gestational Age–Matched Case Study

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2009-02, Vol.53 (2, Part 2 Suppl), p.393-398
• Main Authors: Herse, Florian, Verlohren, Stefan, Wenzel, Katrin, Pape, Juliane, Muller, Dominik N, Modrow, Susanne, Wallukat, Gerd, Luft, Friedrich C, Redman, Christopher W.G, Dechend, Ralf
• Format: Article
• Language: English
• Subjects: Adult; Arterial hypertension. Arterial hypotension; Autoantibodies - blood; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Capsid Proteins - immunology; Cardiology. Vascular system; Case-Control Studies; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Female; Gestational Age; Humans; Immunoglobulin G - blood; Medical sciences; Parvovirus B19; Pre-Eclampsia - blood; Pre-Eclampsia - immunology; Pregnancy; Prospective Studies; Receptor, Angiotensin, Type 1 - immunology; Vascular Endothelial Growth Factor Receptor-1 - blood
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.108.124115

We showed earlier that activating autoantibodies against the angiotensin II type 1 (AT1) receptor (AT1-AA) circulate in preeclamptic women. They may be involved in the pathogenesis of preeclampsia. Protein alignment suggests that the binding site for AT1-AAs is highly homologous to the capsid protein VP2 of parvovirus B19. We performed a prospective, nested, case-control study of 30 gestational age–matched women with preeclampsia and 30 normotensive pregnant women. We measured AT1-AA, soluble fms-like tyrosine kinase 1 (sFlt-1), and serum immunoglobulin G against parvovirus B19 proteins. AT1-AAs were present in 70% of preeclamptic patients and absent in 80% of controls. Prediction by AT1-AA was improved in late-onset preeclampsia. The discrimination for sFlt-1 was 96%. We did not find an interaction between sFlt-1 and AT1-AA. A human monoclonal immunoglobulin G antibody against parvovirus B19 VP2-protein showed a positive reaction in the AT1-AA bioassay, which could be blocked by an AT1 receptor blocker, as well as by the epitope amino acid sequence. Immunoglobulin G against parvovirus B19 proteins was similarly distributed between preeclamptic patients and controls and had no significant importance. We detected significantly more AT1-AA in women with an immune response corresponding with parvovirus B19 infection corresponding with a distant viral infection associated with virus elimination. We concluded that AT1-AAs were common in patients with preeclampsia in a prospective case-control study, although sFlt-1 was a superior biomarker. AT1-AA may represent a better marker for late disease, whereas sFlt1 is a better marker for early onset disease.