Until recently the investigation of serological responses to mycobacteria in patients with Crohn's disease has been hindered by the considerable degree of cross-reactivity between antigens of M. paratuberculosis, and other mycobacterial subspecies. We evaluated the serological response of Crohn's disease patients to a recently identified species-specific 18 kDa protease-resistant antigen corresponding to M. paratuberculosis bacterioferritin. The 18 kDa antigen was purified from M. paratuberculosis as previously described. Serum was obtained from 40 patients with Crohn's disease, 15 with ulcerative colitis, 25 coeliac patients, and 21 normal blood donors. Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), with anti-human IgA and IgG alkaline phosphatase conjugate. Antibody titres were expressed as the dilution giving 1/3 of the plateau binding value of a standard positive serum (MT/3). Disease activity of the Crohn's disease cases was assessed using the Harvey-Bradshaw index. There was no statistically significant elevation of the mean IgG or IgA MT/3 titres of Crohn's disease patients over controls. No patients had antibody titres greater than two standard deviations above the mean control MT/3 titres, and there was no significant correlation between Crohn's disease activity and level of antibody titres. These findings make it unlikely that M. paratuberculosis is of primary pathogenic importance in Crohn's disease.

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