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Population-Based Case Control Study of Seroprevalence of Mycobacterium paratuberculosis in Patients with Crohn's Disease and Ulcerative Colitis

Inflammatory Bowel Disease Clinical and Research Centre,¹ Departments of Internal Medicine,² Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada,³ The Department of Microbiology, University of Wisconsin at Madison, Madison, Wisconsin⁴

Received 22 August 2003/ Returned for modification 2 November 2003/ Accepted 14 November 2003

There is renewed enthusiasm for exploring the possibility that Mycobacterium paratuberculosis may be causative in Crohn's disease (CD). We aimed to determine whether CD subjects are more likely to be M. paratuberculosis seropositive than controls. Using our population-based University of Manitoba Inflammatory Bowel Disease Research Registry, we recruited CD and ulcerative colitis (UC) subjects between 18 and 50 years of age for a study involving detailed questionnaires and venipuncture. We accessed the population-based databases of Manitoba Health (single provincial health insurer) to get age-, gender-, and geography-matched controls to our inflammatory bowel disease (IBD) population. We asked enrolling IBD subjects for potential nonaffected sibling controls. We used an enzyme-linked immunosorbent assay (ELISA) for serum antibodies to M. paratuberculosis initially developed for cattle but adapted for human use. The rate of positive ELISA results, based on previously published interpretation criteria, was significantly higher for all study groups. There was no difference in M. paratuberculosis seropositivity rate among CD patients (37.8%; n = 283), UC patients (34.7%; n = 144), healthy controls (33.6%; n = 402), and nonaffected siblings (34.1%; n = 138). For siblings, there was no correlation between M. paratuberculosis serological status and that of the corresponding IBD affected sibling. None of the demographic or questionnaire variables studied were predictive of M. paratuberculosis status. Subjects with CD and UC were less likely to have ingested unpasteurized milk and less likely to have had a non-tap water source as a primary water source. In conclusion, in this population-based case control study, the M. paratuberculosis seropositivity rate was approximately 35% for all groups and there was no difference in rates between CD patients, UC patients, healthy controls, or nonaffected siblings. The much higher rate of seropositivity for subjects from Manitoba, Canada, than for those from Denmark or Wisconsin cannot be obviously explained. While these data seem to refute any association of CD with M. paratuberculosis, the high seroprevalence in Manitobans raises the possibility that the high rates of CD in Manitoba could be related to high exposure rates for M. paratuberculosis. Hence, the possibility of an association between M. paratuberculosis and CD remains inconclusive.

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