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Title: On the etiology of Crohn disease.
Title Abreviation: Proc Natl Acad Sci U S A Date of Pub: 1996 Sep 3
Author: Mishina D; Katsel P; Brown ST; Gilberts EC; Greenstein RJ;
Issue/Part/Supplement: 18 Volume Issue: 93 Pagination: 9816-20
MESH Headings: Autoradiography; Base Sequence; Cohort Studies; Crohn Disease (*ET/GE/MI); DNA (AN); Human; Ileum (CH/PA); Intestinal Mucosa (CH/PA); Molecular Sequence Data; Mycobacterium paratuberculosis; Paratuberculosis (CO); Polymerase Chain Reaction; RNA (AN); -RN-;
Journal Title Code: PV3 Publication Type: JOURNAL ARTICLE
Date of Entry: 961024NEntry Month: 9612
Country: UNITED STATES Index Priority: 2
Language: Eng Unique Identifier: 96382550
Unique Identifier: 96382550 ISSN: 0027-8424
Abstract: Crohn disease (CD) is a chronic, panenteric intestinal inflammatory disease. Its etiology is unknown. Analogous to the tuberculoid and lepromatous forms of leprosy, CD may have two clinical manifestations. One is aggressive and fistulizing (perforating), and the other is contained, indolent, and obstructive (nonperforating) [Gilberts, E. C. A. M., Greenstein, A. J., Katsel, P., Harpaz, N. & Greenstein, R. J. (1994) Proc. Natl. Acad. Sci. USA 91, 12721-127241. The etiology, if infections, may be due to Mycobacterium paratuberculosis. We employed reverse transcription PCR using M. paratuberculosis subspecies-specific primers (IS 900) on total RNA from 12 ileal mucosal specimens (CD, n = 8; controls, n = 4, 2 with ulcerative colitis and 2 with colonic cancer). As a negative control, we used Myobacterium avium DNA, originally cultured from the drinking water of a major city in the United States. cDNA sequence analysis shows that all eight cases of Crohn's disease and both samples from the patients with ulcerative colitis contained M. paratuberculosis RNA. Additionally, the M. avium control has the DNA sequence of M. paratuberculosis. We demonstrate the DNA sequence of M. paratuberculosis 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 relationship has not been established. In part, this is due to conflicting data from studies with empirical antimycobacterial therapy. We conclude that clinical trials with anti-M. paratuberculosis therapy are indicated in patients with CD who have been stratified into the aggressive (perforating) and contained (nonperforating) forms.
Abstract By: Author
Address: Laboratory of Molecular Surgical Research, Veterans Affairs Medical Center, Bronx, NY 10468, USA.