Abnormal urothelial HLA-DR expression in interstitial cystitis

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Abstract
SUMMARY: Interstitial cystitis is a chronic inflammatory disorder of the urinary bladder that predominantly afflicts middle-age women. The end stage of the disease is ulceration of the urothelium, the so-called Hunner's ulcer. The aetiology of interstitial cystitis remains obscure. We have studied bladder biopsies from 22 cases of interstitial cystitis and control groups consisting of six cases of bacterial cystitis and eight healthy women. Indirect immunofluorescence was performed on the biopsies using murine MoAbs to human HLA class I molecules, and class II molecules, HLA-DP, HLA-DQ and HLA-DR. In interstitial cystitis, bacterial cystitis and normal controls most cells expressed HLA class I products. In six cases of interstitial cystitis and one case of bacterial cystitis there was evidence of HLA class I hyperexpression. In normal bladder and bacterial cystitis HLA class II expression was restricted to submucosal dendritic cells. Langerhans cells macrophages, vascular endothelial cells and activated lymphocytes. All but two cases of interstitial cystitis showed surface expression of HLA-DR (but not HLA-DP or DQ). In all cases of interstitial cystitis there was an increase in the numbers of macrophages, activated lymphocytes and vascular endothelial cells expressing HLA class II molecules within the submucosa. These findings provide further evidence for the importance of inappropriate HLA molecule expression in a disease suspected of having an autoimmune pathogenesis and where cellular autoimmune mechanisms play a decisive role in the destruction of the target cells - the bladder urothelium.