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Autoantibody‐mediated Bladder Dysfunction in Type 1 Diabetes
Author(s) -
Wan E.C.,
Gordon T. P.,
Jackson M. W.
Publication year - 2007
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01877.x
Subject(s) - medicine , dihydropyridine , nicardipine , diabetes mellitus , urinary bladder , agonist , voltage dependent calcium channel , endocrinology , bladder outlet obstruction , overactive bladder , autoantibody , immunology , antibody , calcium , receptor , pathology , prostate , alternative medicine , cancer
Bladder dysfunction is a common complication of diabetic autonomic neuropathy; however, its cause remains uncertain. We have recently identified a novel IgG autoantibody (Ab) in patients with type 1 diabetes that acts as an agonist at the dihydropyridine (DHP) site of L‐type voltage‐gated calcium channels (VGCC), disrupting neuronal regulation of visceral smooth muscle. In the present study, passive transfer to mice of IgG from patients with type 1 diabetes was used to investigate the role of anti‐VGCC Abs in mediating diabetic bladder dysfunction. Injection of mice with diabetic immunoglobulin (IgG) with anti‐VGCC activity induced features of an overactive bladder, including phasic detrusor contractions and a loss of bladder wall compliance. The bladder overactivity is mimicked by the DHP agonist Bay K8644, reversed by the DHP antagonist nicardipine, but is insensitive to the motor nerve blocker tetrodotoxin, indicating that the anti‐VGCC Ab acts at the level of the bladder detrusor itself. This study reports the first evidence of Ab‐mediated bladder dysfunction in type 1 diabetes, which may be part of a wider spectrum of smooth muscle and cardiac abnormalities.