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Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor
Open accessAbstract
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.
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Citations
Cited by
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Physiology of Local Renin-Angiotensin Systems
Paul, M., Poyan Mehr, A., & Kreutz, R. (2006) · Physiological Reviews · doi:10.1152/physrev.00036.2005 · Cited by 1,739
The effects of oxidative stress on female reproduction: a review
Agarwal, A., Aponte-Mellado, A., Premkumar, B. J., Shaman, A., & Gupta, S. (2012) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-10-49 · Cited by 1,637
Pre-eclampsia part 1: current understanding of its pathophysiology
Chaiworapongsa, T., Chaemsaithong, P., Yeo, L., & Romero, R. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.102 · Cited by 956
Angiotensin II Type 1–Receptor Activating Antibodies in Renal-Allograft Rejection
Dragun, D., Müller, D. N., Bräsen, J. H., Fritsche, L., Nieminen-Kelhä, M., Dechend, R., Kintscher, U., Rudolph, B., Hoebeke, J., Eckert, D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa035717 · Cited by 868
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Metadata
- Authors
- Wallukat, G., Homuth, V., Fischer, T., Lindschau, C., Horstkamp, B., Jüpner, A., Baur, E., Nissen, E., Vetter, K., Neichel, D., Dudenhausen, J. W., Haller, H., & Luft, F. C.
- Venue
- Journal of Clinical Investigation
- Published
- 1999-04-01
- Volume
- 103
- Issue
- 7
- Pages
- 945-952
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2089221056
- Cited by
- 826
- References
- 0
- FWCI
- 11.44
- Type
- journal article
- Language
- en
- Open access
- green
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- Wallukat, G., Homuth, V., Fischer, T., Lindschau, C., Horstkamp, B., Jüpner, A., Baur, E., Nissen, E., Vetter, K., Neichel, D., Dudenhausen, J. W., Haller, H., & Luft, F. C. (1999). Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. Journal of Clinical Investigation. https://doi.org/10.1172/jci4106
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