title: Identification of a Novel Agonist-Like Autoantibody in Preeclamptic Patients.
abstract: BACKGROUND
  Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of PE.
  
  
  METHODS
  To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists.
  
  
  RESULTS
  Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype.
  
  
  CONCLUSIONS
  We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE.
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Elizabeth Portugal
authors.initials: EP
authors.lastname: Velloso
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Renata Lúcia
authors.initials: RL
authors.lastname: Pimentel
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Janaína F
authors.initials: JF
authors.lastname: Braga
authors.affiliation: Department of Gynecology and Obstetrics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Antônio Carlos Vieira
authors.initials: AC
authors.lastname: Cabral
authors.affiliation: Department of Gynecology and Obstetrics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Zilma Silveira N
authors.initials: ZS
authors.lastname: Reis
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; robsonsant@gmail.com.
authors.forename: Robson Augusto S
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D016022:Case-Control Studies; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077405:Irbesartan; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000276:immunology; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000276:immunology; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000494:pharmacology; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010456:Peptides, Cyclic; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D013777:Tetrazoles; D011493:Protein Kinase C; C058819:calphostin C; D000077405:Irbesartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
keywords: autoantibodies; blood pressure; endothelin; hypertension; preemclampsia.