title: 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.
abstract: We showed earlier that activating autoantibodies against the angiotensin II type 1 (AT(1)) 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 AT(1) 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.
authors.affiliation: Medical Faculty of the Charité, Franz-Volhard Clinic, HELIOS Klinikum Berlin-Buch and Experimental and Clinical Research Center, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.forename: Stefan
authors.initials: S
authors.lastname: Verlohren
authors.forename: Katrin
authors.initials: K
authors.lastname: Wenzel
authors.forename: Juliane
authors.initials: J
authors.lastname: Pape
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Muller
authors.forename: Susanne
authors.initials: S
authors.lastname: Modrow
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Christopher W G
authors.initials: CW
authors.lastname: Redman
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D036022:Capsid Proteins / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D036022:Capsid Proteins; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; C095548:capsid protein VP2, parvovirus B19; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1