Population-Based Case Control Study of Seroprevalence ofMycobacterium paratuberculosisin Patients with Crohn's Disease and Ulcerative Colitis

Abstract

There is renewed enthusiasm for exploring the possibility thatMycobacterium paratuberculosismay be causative in Crohn's disease (CD). We aimed to determine whether CD subjects are more likely to beM. paratuberculosisseropositive 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 toM. paratuberculosisinitially 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 inM. paratuberculosisseropositivity 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 betweenM. paratuberculosisserological status and that of the corresponding IBD affected sibling. None of the demographic or questionnaire variables studied were predictive ofM. paratuberculosisstatus. 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, theM. paratuberculosisseropositivity 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 withM. paratuberculosis, the high seroprevalence in Manitobans raises the possibility that the high rates of CD in Manitoba could be related to high exposure rates forM. paratuberculosis. Hence, the possibility of an association betweenM. paratuberculosisand CD remains inconclusive.