The role of CD40 in ulcerative colitis: histochemical analysis and clinical correlation

OBJECTIVES : CD40 co-stimulator seems to be implicated in the loss of tolerance against self-antigens in many autoimmune diseases. The evidence suggests that in the pathogenesis of ulcerative colitis there is an activity state against self-antigens of the gut wall and flora. The aim of this study was to analyse the expression of CD40 in ulcerative colitis, comparing it with Crohn's disease and nonspecific inflammation of the colon and to determine whether there is a relationship between its expression and the activity stage of the disease. METHODS : The expression of CD40 in the colonic samples of 51 patients (30 ulcerative colitis, 9 Crohn's disease and 12 nonspecific inflammation) was analysed by immunohistochemistry. Twenty-four patients with ulcerative colitis were scored according to clinical, endoscopic and histological classification. RESULTS : The mean percentage of CD40+ cells per field in the colonic mucosa was: ulcerative colitis 21 +/- 11%, Crohn's disease 24 +/- 9%, nonspecific inflammation 7 +/- 7%. The ulcerative colitis patients were statistically significantly different compared to the patients with nonspecific inflammation (P < 0.005), even when comparing the patients in remission (P < 0.05). The expression in Crohn's disease was similar to that in ulcerative colitis. The expression of CD40 in ulcerative colitis was directly proportional to the state of activity of the disease according to the clinical (P < 0.02), endoscopic (P < 0.01) and histological (P < 0.02) criteria. CONCLUSIONS : The expression of CD40 in the colonic mucosae of patients with ulcerative colitis is significantly increased and is proportional to the state of activity. The results seem to confirm the hypothesis that a loss of tolerance could be involved in the pathogenesis of this disease.