Publication Date:
2016-11-25
Description:
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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 © 2016 Wiley Periodicals, Inc.
Print ISSN:
0270-4137
Electronic ISSN:
1097-0045
Topics:
Medicine
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