MUCOSAL COMPLEMENT DEPOSITION IN INFLAMMATORY BOWEL-DISEASE

Mucosal deposition of activated complement and immunoglobulin (Ig) in inflammatory bowel disease (IBD) was examined by indirect two- and thr ee-colour immunofluorescence staining applied on sections of ethanol-f ixed or frozen tissue specimens from patients with ulcerative colitis or Crohn's disease. Monoclonal antibodies (mAbs) to IgG subclasses and neoepitopes of activated C3b or terminal complement complex (TCC) wer e used in combination with rabbit antiserum to various complement comp onents (C1q, C3c, C3dg, C4c). Activated C3b was found on the luminal f ace of the surface epithelium in the most affected ulcerative colitis specimens from 91 % of 23 patients, together with cytolytic TCC in 8.1 %. Similar deposition was observed in 50% of 18 patients with Crohn's disease. However, co-deposition of the IgG1 subclass and complement c omponents involved in the classical activation pathway (C1q and C4c) w as seen only in ulcerative colitis and in complement components involv ed in the classical activation pathway (C1q and C4c). Moreover, in ulc erative colitis these epithelial immune complexes often co-localized w ith a previously identified M(r) 40 kDa putative autoantigen (mAb 7E12 H12). Additional type III immune reaction might take place in both dis eases because evidence of continuous vascular complement activation ha s been seen in submucosal blood vessels. The results demonstrated that local complement activation takes place in IBD lesions. While epithel ial deposition of IgG1 and activated complement suggested an autoimmun e attack in ulcerative colitis, the absence of IgG1, C1q and C4c in Cr ohn's disease was rather consistent with the alternative activation pa thway.