Final Progress Report

Proposal No. IBD-0074R
Principal Investigator:  Marcel A. Behr, M.D.
Applicant Organization:  McGill University Health Centre Research Institute (Montreal, Canada)
Project Title:  Molecular and immunologic detection of Mycobacterium avium paratuberculosis in Crohn's disease
Period of Award:  December 1, 2003 - March 31, 2006

Lay summary

It has long been postulated that Crohn’s disease may result from an infectious process, and specifically, the mycobacterial family of organisms has been implicated because of some similarities between a mycobacterial disease of cattle (called Johne’s disease) and human Crohn’s disease. However, this link has been difficult to establish or refute. The goal of the work funded by the Broad Medical Research Program was to use human samples to look for evidence of mycobacterial infection, using a number of different methods.

In order to be certain that the methods applied provided unambiguous results, in terms of presence or absence of this organism, experimental infections of mice were performed, permitting us to compare different tests head-to-head in a setting where the infection status was known. Organs from these infected mice were then subject to a number of studies, providing us with certain clues as to which methods would best serve for human epidemiologic studies.

The most specific findings of our work were that certain molecular tests, looking for bacterial DNA, cannot be shown to be better than more conventional forms of testing, such as culturing organisms in a microbiology laboratory. Additionally, the methods we have applied provide a template for any further studies on this organism, as arguably no investigation of humans should commence prior to the methods being shown to be reliable when applied to tissue from experimentally-infected animals or uninfected controls. Based on the methods tested, we have now selected the most specific laboratory tests and are currently evaluating their ability to detect these organisms in infected tissue from Crohn’s patients.