title: Autoantibodies Directed Against the Endothelin A Receptor in Patients With Benign Prostatic Hyperplasia.
abstract: Over-stimulation of G-protein coupled receptors (GPCRs) such as α1-adrenergic, muscarinic, endothelin, and AT1 receptors is considered to drive benign prostatic hyperplasia (BHP) which is often associated with lower urinary tract syndrome (LUTS). However, in addition to physiologic GPCR ligands, there is a new class of autoantibodies called functional autoantibodies that target the same GPCRs (GPCR-AABs) for over-stimulation, thus, presenting pathogenic potency. We hypothesize that patients with BPH/LUTS could carry GPCR-AABs representing potential targets for treatment.
  
  
  
  GPCR-AABs were identified, quantified, and characterized in the serum from 20 patients (aged 55-82 years, median 71 years) with BPH using the bioassay of spontaneously beating cultured neonatal rat cardiomyocytes.
  
  
  
  A sum of 60% of the patients were positive for agonistic autoantibodies directed against the endothelin A receptor (ETA-AABs). ETA-AABs were associated with the IgG 1 subclass, targeted an epitope located on the second extracellular receptor loop and their agonistic activity could be neutralized by the aptamer BC007.
  
  
  
  Agonistic ETA-AABs could-via uncontrolled over-boarding endothelin A receptor stimulation-contribute to the pathogenesis of BPH/LUTS. The in vitro demonstrated ETA-AAB neutralization by the aptamer BC007 could open the door for a new treatment strategy in patients with BPH/LUTS. Prostate 77:458-465, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Berlin Cures GmbH, Berlin, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.affiliation: Universitätsklinik für Urologie und Kinderurologie, Otto von Guericke Universität, Magdeburg, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Jandrig
authors.affiliation: Science Office, Berlin-Buch, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kunze
authors.affiliation: Universitätsklinik für Urologie und Kinderurologie, Otto von Guericke Universität, Magdeburg, Germany.
authors.forename: Johann J
authors.initials: JJ
authors.lastname: Wendler
authors.affiliation: Berlin Cures GmbH, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Müller
authors.affiliation: Universitätsklinik für Urologie und Kinderurologie, Otto von Guericke Universität, Magdeburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schostak
authors.affiliation: Berlin Cures GmbH, Berlin, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Schimke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D051381:Rats; D044022:Receptor, Endothelin A / Q000097:blood* / Q000235:genetics
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D044022:Receptor, Endothelin A
keywords: G-protein coupled receptors; aptamer; autoimmunity