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(Hypertension. 2009;53:393.)
© 2009 American Heart Association, Inc.

Original Articles Part 2

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

Florian Herse; Stefan Verlohren; Katrin Wenzel; Juliane Pape; Dominik N. Muller; Susanne Modrow; Gerd Wallukat; Friedrich C. Luft; Christopher W.G. Redman; Ralf Dechend

From the Medical Faculty of the Charité (F.H., S.V., K.W., D.N.M., G.W., F.C.L., R.D.), Franz-Volhard Clinic, HELIOS Klinikum Berlin-Buch and Experimental and Clinical Research Center, Berlin, Germany; Department of Obstetrics (S.V., J.P.), Charité Campus Virchow-Clinic, Charité University Medicine, Berlin, Germany; Institute for Medical Microbiology and Hygiene (S.M.), University of Regensburg, Regensburg, Germany; and the Nuffield Department of Obstetrics and Gynaecology (C.W.G.R.), Oxford University, John Radcliffe Hospital, Oxford, United Kingdom.

Correspondence to Ralf Dechend, Experimental and Clinical Research, Charite, Campus-Buch and HELIOS Clinic, Lindenberger Weg 80, 13125 Berlin, Germany. E-mail ralf.dechend{at}charite.de

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.

Key Words: preeclampsia • activating autoantibodies • angiogenesis • parvovirus B19 • molecular mimicry