Identification of a Novel Agonist-Like Autoantibody in Preeclamptic XXXX .

@entity1 @entity7056 @entity1468 @entity11344 @entity35 @entity11616
BACKGROUND: Recent studies have shown that @entity1468 ( @entity1468 ) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of @entity1468 . METHODS: To investigate the frequency and the targets of AABs in preeclamptic @entity1 (31 cases) and healthy pregnant normotensive @entity1 (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal @entity35 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 @entity1 (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by @entity7056 and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic @entity1 (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 @entity11344 , antagonized by the protein kinase C (PKC) inhibitor @entity11616 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 @entity1468 . Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe @entity1468 .
