Persistent Complement Activation in Submucosal Blood Vessels of Active Inflammatory Bowel Disease: Immunohistochemical Evidence

Extensively washed and ethanol-fixed colonic specimens from 10 patients with ulcerative colitis, 3 patients with Crohn's disease of the colon, and 8 histologically normal controls were examined by two-color immunohistochemistry with monoclonal antibody to a neoepitope in the terminal complement complex combined with antiserum to factor VIII-related antigen (von Willebrand's factor), C3c, C3d, or C5. An alternative combination was monoclonal antibody to S-protein and antiserum to C9. Submucosal vessel walls in both normal and diseased colon showed parallel positivity for C3d, C5, C9, terminal complement complex, and S-protein, but the staining intensity and the proportion of positive vessels were significantly higher in inflammatory bowel disease than in controls. In addition, there was significantly more C3c reactivity associated with the terminal complement complex-positive submucosal vessels of active inflammatory bowel disease lesions than in histologically normal colon. Vascular C activation may therefore be a continuous process in active inflammatory bowel disease lesions, presumably related to the degree of inflammation and immune complex formation.