3rd Annual BMRP Investigator Meeting - Abstract

Mycobacterium avium subspecies paratuberculosis – Does It Have a Role in the Pathogenesis of Crohn’s Disease?

Robert Clancy

Discipline of Immunology and Microbiology, University of Newcastle (Newcastle, Australia)

The hypothesis tested in this study was that Mycobacterium avium subspecies paratuberculosis (MAP) can initiate mucosal inflammation in Crohn’s disease (CD) in a non-exclusive fashion and in a framework of genetic host defect(s) (i.e., that two current theories of pathogenesis are not mutually exclusive).  Three questions were addressed: a) Is MAP detection in CD of clinical value? b) Is there defective host handling of MAP? and c) Does anti-MAP therapy reverse parameter of mucosal inflammation?  A cross section and a prospective study were designed in the proposed two-year program.

This report describes results at eight months of the cross-sectional study:  (i) A functional lab has been established in a busy gastroenterology unit capable of on-site handling of mucosal cultures.  (ii) 137 subjects have been studied: normal (63), irritable bowel syndrome (26), ulcerative colitis (22), and Crohn’s disease (26).  (iii) MAP +ve by PCR:  N 14%; IBS 19%; UC 14%; CD 23% (therapy no obvious influence).  (iv) Mucosal organ culture (assay cytokines: IL-12, INF-γ, IL-10, IL-2).  In CD, there was less secretion of INF-γ (24pg/ml) than in ulcerative colitis (84pg/ml, P=0.038) and normal gut (73pg/ml, P=0.14) and less secretion of IL-10 (17pg/ml) than in normal gut (23pg/ml, P=0.041).  (v) Whole blood culture stimulated by MAP antigen:  INF-g secretion reduced in response to soluble MAP (1ug/l) in CD c/w all groups (CD 22, Normal gut 39; IBS 98, UC 52pg/ml).  IL-2, IL-12, and secretion were similar in all groups.

Conclusion:

   i.    A new organ culture method identifies a specific mucosal cytokine secretion pattern.
   ii.    MAP is detected in a minority of CD subjects using mucosal biopsy.
   iii.    MAP reactive blood T cells secrete less INF-γ and IL-10 than other clinical groups.
   iv.    Ongoing studies to expand and elaborate on these observations will be discussed.