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

Item Type:	Article
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
Creators Name:	Herse, F. and Verlohren, S. and Wenzel, K. and Pape, J. and Mueller, D.N. and Modrow, S. and Wallukat, G. and Luft, F.C. and Redman, C.W. and Dechend, R.
Abstract:	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.
Keywords:	Preeclampsia, Activating Autoantibodies, Angiogenesis, Parvovirus B19, Molecular Mimicry
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	53
Number:	2
Page Range:	393-398
Date:	February 2009
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.108.124115
PubMed:	View item in PubMed

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