TY - JOUR
T1 - Gene expression profiles of ileal inflammatory bowel disease correlate with disease phenotype and advance understanding of its immunopathogenesis
AU - Ben-Shachar, Shay
AU - Yanai, Henit
AU - Baram, Liran
AU - Elad, Hofit
AU - Meirovithz, Elhanan
AU - Ofer, Amos
AU - Brazowski, Eli
AU - Tulchinsky, Hagit
AU - Pasmanik-Chor, Metsada
AU - Dotan, Iris
PY - 2013/11
Y1 - 2013/11
N2 - Background: Pouchitis may develop in patients with ulcerative colitis undergoing pouch surgery. We aimed to evaluate the de novo inflammation developing in the ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease (CD). Methods: Patients with ulcerative colitis pouch were prospectively recruited, stratified according to disease behavior into normal pouch, chronic pouchitis, and Crohn's-like disease of the pouch groups, and compared with controls. Gene expression analysis was performed using microarrays, validated by real-time polymerase chain reaction. Gene ontology and clustering were evaluated using bioinformatic tools. Results: Sixty-six subjects were recruited. Although in ulcerative colitis ileum there were no significant gene expression alterations, patients with normal pouch had 168 significant alterations (fold change ≥ 2, corrected P ≤ 0.05). In chronic pouchitis and Crohn's-like disease of the pouch, 490 and 1152 alterations were detected, respectively. High degree of overlap in gene expression alterations between the pouch subgroups was demonstrated. The magnitude of change correlated with pouch disease behavior. Gene expression profiles were more reflective of disease behavior compared with inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with pouchitis. Gene ontology analyses revealed multiple biological processes associated with pouch inflammation, including response to chemical stimulus, small molecule metabolic and immune system processes, and specific infection-related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis. Conclusions: Gene alterations in pouch inflammation and CD overlap, suggesting that inflammatory bowel diseases is a spectrum, rather than distinct diseases. Pouchitis may serve as a model of CD. The novel pathways associated with inflammatory bowel diseases may decipher pathophysiology and suggest targets for intervention.
AB - Background: Pouchitis may develop in patients with ulcerative colitis undergoing pouch surgery. We aimed to evaluate the de novo inflammation developing in the ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease (CD). Methods: Patients with ulcerative colitis pouch were prospectively recruited, stratified according to disease behavior into normal pouch, chronic pouchitis, and Crohn's-like disease of the pouch groups, and compared with controls. Gene expression analysis was performed using microarrays, validated by real-time polymerase chain reaction. Gene ontology and clustering were evaluated using bioinformatic tools. Results: Sixty-six subjects were recruited. Although in ulcerative colitis ileum there were no significant gene expression alterations, patients with normal pouch had 168 significant alterations (fold change ≥ 2, corrected P ≤ 0.05). In chronic pouchitis and Crohn's-like disease of the pouch, 490 and 1152 alterations were detected, respectively. High degree of overlap in gene expression alterations between the pouch subgroups was demonstrated. The magnitude of change correlated with pouch disease behavior. Gene expression profiles were more reflective of disease behavior compared with inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with pouchitis. Gene ontology analyses revealed multiple biological processes associated with pouch inflammation, including response to chemical stimulus, small molecule metabolic and immune system processes, and specific infection-related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis. Conclusions: Gene alterations in pouch inflammation and CD overlap, suggesting that inflammatory bowel diseases is a spectrum, rather than distinct diseases. Pouchitis may serve as a model of CD. The novel pathways associated with inflammatory bowel diseases may decipher pathophysiology and suggest targets for intervention.
KW - Crohn's disease
KW - IBD
KW - Inflammatory pathways
KW - Pouchitis
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=84888313370&partnerID=8YFLogxK
U2 - 10.1097/01.MIB.0000437045.26036.00
DO - 10.1097/01.MIB.0000437045.26036.00
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C2 - 24108111
AN - SCOPUS:84888313370
SN - 1078-0998
VL - 19
SP - 2509
EP - 2521
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 12
ER -