Immunopathology of interstitial cystitis

This study describes histologic, ultrastructural, and immunofluorescence microscopy findings of cystoscopically directed biopsies of lesional tissue and uninvolved bladder from 308 patients with chronic interstitial cystitis (IC) and no evidence of infection, collagen vascular, or other systemic disease. The majority of cases exhibited strong urothelial cell staining for immunoglobulin A (IgA), which was focal or diffusely involved all layers of the epithelium. Electron microscopy revealed widening of the interstitium between urothelial cells, which may explain leakage of IgA into the urine in cystitis patients. Staining for fibrinogen and IgA was present both in lesional biopsies and uninvolved bladder tissue, suggesting a response to injury affecting the entire bladder urothelium. A minor patient population with idiopathic IC revealed granular IgM (with or without C3) in vessel walls of the lamina propria, suggesting immune complex disease. Ultrastructural evidence of vascular damage included necrosis of endothelial cells, fibrin deposition, and reduplication of basement membranes. Staining for IgE correlated with presence of mast cells and was present in less than 2% of cases, indicating that these cells do not play a prominent role in the pathogenesis of the disease. In the majority of patients with IC mucosal staining for IgA and fibrinogen was a characteristic pattern representing increased IgA secretion and a reaction pattern to injury of unknown cause. A subgroup of patients had evidence of vascular damage and immune complex disease. This study therefore defines two main reaction patterns in interstitial cystitis, which may have implications on prognosis and therapy of the disorder.