ON THE ETIOLOGY OF CROHN DISEASE

Crohn disease (CD) is a chronic, panenteric intestinal inflammatory di sease. Its etiology is unknown. Analogous to the tuberculoid and lepro matous forms of leprosy, CD may have two clinical manifestations. One is aggressive and fistulizing (perforating), and the other is containe d, indolent, and obstructive (nonperforating) [Gilberts, E. C. A. M., Greenstein, A. J., Katsel, P., Harpaz, N. & Greenstein, R. J. (1994) P roc. Natl. Acad. Sci. USA 91, 12721-12724]. The etiology, if infectiou s, may be due to Mycobacterium paratuberculosis. We employed reverse t ranscription PCR using paratuberculosis subspecies-specific primers (I S 900) on total RNA from 12 ileal mucosal specimens (CD, n = 8; contro ls, n = 4, 2 with ulcerative colitis and 2 with colonic cancer). As a negative control, we used Myobacterium avium DNA, originally culture f rom the drinking water of a major city in the United States. cDNA sequ ence analysis shows that all eight cases of Crohn's disease and both s amples from the patients with ulcerative colitis contained M. paratube rculosis RNA. Additionally, the M. avium control has the DNA sequence of M. paratuberculosis. We demonstrate the DNA sequence of M. paratube rculosis from mucosal specimens from humans with CD. The potable water supply may be a reservoir of infection. Although M. paratuberculosis signal in CD has been previously reported, a cause and effect relation ship has not been established. In part, this is due to conflicting dat a from studies with empirical antimycobacterial therapy. We conclude t hat clinical trials with anti-M. paratuberculosis therapy are indicate d in patients with CD who have been stratified into the aggressive (pe rforating) and contained (nonperforating) forms.