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Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion.
Dig Liver Dis 2007; 39(5):445-51DL

Abstract

BACKGROUND

Support for a role of Mycobacterium avium subspecies paratuberculosis in Crohn's disease is largely based on epidemiological evidence, as no data on mechanisms linking the presence of M. avium subspecies paratuberculosis with gut damage is available.

AIMS

To determine whether the presence of M. avium subspecies paratuberculosis contributes to the pathogenesis of Crohn's disease by promoting cytokine secretion within gut mucosa.

PATIENTS AND METHODS

A total of 235 subjects were recruited: 63 with Crohn's disease, 53 with ulcerative colitis, 45 with irritable bowel syndrome and 74 normal controls. M. avium subspecies paratuberculosis status was defined by nested PCR using IS900 sequence. Gut mucosal organ cultures were established to detect cytokine secretion patterns.

RESULTS

Significantly higher tumour necrosis factor-alpha concentrations were found in culture supernatants for Crohn's disease compared to ulcerative colitis (p<0.05), irritable bowel syndrome (p<0.01) and controls (p<0.0001). When tumour necrosis factor-alpha levels were correlated with the presence of M. avium subspecies paratuberculosis, significantly greater concentrations were only found in M. avium subspecies paratuberculosis-positive Crohn's disease patients (p<0.05). Tumour necrosis factor-alpha levels in M. avium subspecies paratuberculosis-positive Crohn's disease were significantly higher than in M. avium subspecies paratuberculosis-positive ulcerative colitis (p<0.01), M. avium subspecies paratuberculosis-positive irritable bowel syndrome (p<0.05) and M. avium subspecies paratuberculosis-positive controls (p<0.01) and all M. avium subspecies paratuberculosis-negative specimens.

CONCLUSIONS

The data link M. avium subspecies paratuberculosis with a pathogenic mechanism in Crohn's disease and is consistent with abnormal macrophage handling of M. avium subspecies paratuberculosis.

Authors+Show Affiliations

Hunter Immunology Unit, Hunter New England Area Health Service, John Hunter Hospital, Newcastle, NSW, Australia. robert.clancy@newcastle.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17317344

Citation

Clancy, R, et al. "Molecular Evidence for Mycobacterium Avium Subspecies Paratuberculosis (MAP) in Crohn's Disease Correlates With Enhanced TNF-alpha Secretion." Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, vol. 39, no. 5, 2007, pp. 445-51.
Clancy R, Ren Z, Turton J, et al. Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion. Dig Liver Dis. 2007;39(5):445-51.
Clancy, R., Ren, Z., Turton, J., Pang, G., & Wettstein, A. (2007). Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion. Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 39(5), pp. 445-51.
Clancy R, et al. Molecular Evidence for Mycobacterium Avium Subspecies Paratuberculosis (MAP) in Crohn's Disease Correlates With Enhanced TNF-alpha Secretion. Dig Liver Dis. 2007;39(5):445-51. PubMed PMID: 17317344.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-alpha secretion. AU - Clancy,R, AU - Ren,Z, AU - Turton,J, AU - Pang,G, AU - Wettstein,A, Y1 - 2007/02/21/ PY - 2006/09/15/received PY - 2006/11/20/revised PY - 2006/12/05/accepted PY - 2007/2/24/pubmed PY - 2007/7/4/medline PY - 2007/2/24/entrez SP - 445 EP - 51 JF - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JO - Dig Liver Dis VL - 39 IS - 5 N2 - BACKGROUND: Support for a role of Mycobacterium avium subspecies paratuberculosis in Crohn's disease is largely based on epidemiological evidence, as no data on mechanisms linking the presence of M. avium subspecies paratuberculosis with gut damage is available. AIMS: To determine whether the presence of M. avium subspecies paratuberculosis contributes to the pathogenesis of Crohn's disease by promoting cytokine secretion within gut mucosa. PATIENTS AND METHODS: A total of 235 subjects were recruited: 63 with Crohn's disease, 53 with ulcerative colitis, 45 with irritable bowel syndrome and 74 normal controls. M. avium subspecies paratuberculosis status was defined by nested PCR using IS900 sequence. Gut mucosal organ cultures were established to detect cytokine secretion patterns. RESULTS: Significantly higher tumour necrosis factor-alpha concentrations were found in culture supernatants for Crohn's disease compared to ulcerative colitis (p<0.05), irritable bowel syndrome (p<0.01) and controls (p<0.0001). When tumour necrosis factor-alpha levels were correlated with the presence of M. avium subspecies paratuberculosis, significantly greater concentrations were only found in M. avium subspecies paratuberculosis-positive Crohn's disease patients (p<0.05). Tumour necrosis factor-alpha levels in M. avium subspecies paratuberculosis-positive Crohn's disease were significantly higher than in M. avium subspecies paratuberculosis-positive ulcerative colitis (p<0.01), M. avium subspecies paratuberculosis-positive irritable bowel syndrome (p<0.05) and M. avium subspecies paratuberculosis-positive controls (p<0.01) and all M. avium subspecies paratuberculosis-negative specimens. CONCLUSIONS: The data link M. avium subspecies paratuberculosis with a pathogenic mechanism in Crohn's disease and is consistent with abnormal macrophage handling of M. avium subspecies paratuberculosis. SN - 1590-8658 UR - https://www.unboundmedicine.com/medline/citation/17317344/Molecular_evidence_for_Mycobacterium_avium_subspecies_paratuberculosis__MAP__in_Crohn's_disease_correlates_with_enhanced_TNF_alpha_secretion_ DB - PRIME DP - Unbound Medicine ER -