Abstract
The cause of interstitial cystitis, a chronic disease that affects the bladder, is unknown. Autoantibodies, such as those against nuclear and bladder epithelium antigens, have been found in patients with interstitial cystitis, but these are likely to be secondary to the disease. No data support a direct causal role of autoimmune reactivity in the pathogenesis of interstitial cystitis. Indirect evidence, however, does support a possible autoimmune nature of interstitial cystitis, such as the strong female preponderance and the clinical association between interstitial cystitis and other known autoimmune diseases within patients and families. The strongest association occurs between interstitial cystitis and Sjögren's syndrome. Increasing evidence suggests a possible role of autoantibodies to the muscarinic M3 receptor in Sjögren's syndrome. The M3 receptor is also located on the detrusor muscle cells of the bladder and mediates cholinergic contraction of the urinary bladder and other smooth muscle tissues. Autoantibodies to the M3 receptor might be important in both the early noninflammatory and the late inflammatory features of interstitial cystitis.
Key Points
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The association within patients and families between interstitial cystitis (IC) and known autoimmune diseases and a female preponderance suggest an autoimmune nature of IC, although direct evidence clearly showing autoimmune mechanisms is lacking
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The strongest association is between IC and Sjögren's syndrome, a disease in which autoantibodies to the muscarinic M3 receptor on exocrine cells are important in the pathogenesis
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Muscarinic M3 receptors are also expressed on detrusor smooth muscle cells, where they mediate cholinergic contraction of the urinary bladder
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Autoantibodies that target muscarinic M3 receptors might therefore have a role in the pathogenesis of IC
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van de Merwe, J. Interstitial cystitis and systemic autoimmune diseases. Nat Rev Urol 4, 484–491 (2007). https://doi.org/10.1038/ncpuro0874
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DOI: https://doi.org/10.1038/ncpuro0874
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