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 three-colour immunofluorescence staining applied on sections of ethanol-fixed 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) were used in combination with rabbit antiserum to various complement components (C1q, C3c, C3dg, C4c). Activated C3b was found on the luminal face 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 components involved in the classical activation pathway (C1q and C4c) was seen only in ulcerative colitis and in complement components involved in the classical activation pathway (C1q and C4c). Moreover, in ulcerative colitis these epithelial immune complexes often co-localized with a previously identified M(r) 40 kDa putative autoantigen (mAb 7E12H12). Additional type III immune reaction might take place in both diseases because evidence of continuous vascular complement activation has been seen in submucosal blood vessels. The results demonstrated that local complement activation takes place in IBD lesions. While epithelial deposition of IgG1 and activated complement suggested an autoimmune attack in ulcerative colitis, the absence of IgG1, C1q and C4c in Crohn's disease was rather consistent with the alternative activation pathway.