Lay Summary

Proposal No.   IBD-0115
Principal Investigator:  Robert L. Clancy, M.D., Ph.D.
Applicant Organization:   The University of Newcastle Research Associates (TUNRA) Limited (Callaghan, New South Wales, Australia)
Project Title:  Mycobacterium avium paratuberculosis (MAP) plays a critical role in the pathogenesis of Crohn’s disease in a substantial proportion of subjects
Period of Award:  April 19, 2004 – April 30, 2006

Despite much study of Crohn’s disease (CD), there remains confusion as to the process that causes the disease.  Current opinion widely favors genetic defects in the integrity of the lining gut mucosa and/or the ‘responsiveness’ of the immune cells within the gut wall (perhaps to gut contents that have leaked through a defective mucosal barrier).  A second possible cause of CD claimed since 1913, has been infection of the gut wall by bacteria known as Mycobacterium avium paratuberculosis (or MAP), which have similarities to those that cause tuberculosis.  An animal disease with similarities to CD, known as Johne’s disease, is caused by MAP, and as infected cows contribute MAP to the food chain, thus much interest has been generated to sort out to what extent, if any, MAP is relevant to CD.  The stumbling block has been the difficulty in isolating MAP in CD – is this methodological, or are positive findings artefactual reflecting contamination of tissues from the environment?

The hypothesis being tested in this proposal is that both the genetic and MAP hypotheses can be relevant in a substantial proportion of subjects.  Methodological issues are being addressed and MAP detection is being correlated with studies on both blood and colon biopsies that examine ‘handling’ of MAP and stimulation of lymphoid cells by MAP components.  In particular, these studies seek to detect an abnormal ‘handling’ of, and response to, MAP infection specifically in patients with CD.  The importance of reliably linking MAP infection with CD is that specific anti-MAP therapy becomes logical with sensitivity to antibiotic panels guiding effective therapy.  If a MAP-specific immune defect is found, additional immune stimulation therapy is encouraged and could enable more efficient eradication of MAP.  Given current controversy over whether or not MAP infection is relevant to CD, well-done studies documenting the presence and relevance of MAP are critically needed.   We plan to develop a quality control program amongst international groups testing for MAP, by coordinating assay technology and including a specimen exchange program.