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Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor

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Item Type:Article
Title:Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor
Creators Name:Wallukat, G. and Homuth, V. and Fischer, T. and Lindschau, C. and Horstkamp, B. and Jupner, A. and Baur, E. and Nissen, E. and Vetter, K. and Neichel, D. and Dudenhausen, J.W. and Haller, H. and Luft, F.C.
Abstract:Immune mechanisms and the renin-angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients and compared them with 12 normotensive pregnant women and 10 pregnant patients with essential hypertension. Antibodies were detected by the chronotropic responses to AT1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists. Immunoglobulin from all preeclamptic patients stimulated the AT1 receptor, whereas immunoglobulin from controls had no effect. The increased autoimmune activity decreased after delivery. Affinity-column purification and anti-human IgG and IgM antibody exposure implicated an IgG antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1 receptor's second extracellular loop abolished the stimulatory effect. Western blotting with purified patient IgG and a commercially obtained AT1 receptor antibody produced bands of identical molecular weight. Furthermore, confocal microscopy of vascular smooth muscle cells showed colocalization of purified patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor calphostin C prevented the stimulatory effect. Our results suggest that preeclamptic patients develop stimulatory autoantibodies against the second extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These novel autoantibodies may participate in the angiotensin II-induced vascular lesions in these patients.
Keywords:Amino Acid Sequence, Angiotensin II, Autoantibodies, Cultured Cells, Heart Ventricles, Immunoglobulin G, Immunoglobulin M, Molecular Sequence Data, Vascular Smooth Muscle, Myocardial Contraction, Naphthalenes, Peptide Fragments, Postpartum Period, Pre-Eclampsia, Pregnancy, Angiotensin Receptors, Animals, Rats
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:945-952
Date:1 April 1999
Official Publication:https://doi.org/10.1172/JCI4106
PubMed:View item in PubMed

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