Unknown,Transcriptomics,Genomics,Proteomics

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Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis

ABSTRACT: Infliximab, an anti-TNF-alpha monoclonal antibody, is an effective treatment for ulcerative colitis (UC) with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-TNF-alpha is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in UC. Keywords: drug response Twenty-four patients with active UC, refractory to corticosteroids and/or immunosuppression, underwent colonoscopy with biopsies from diseased colon within a week prior to the first intravenous infusion of 5 mg infliximab per kg body weight. Response to infliximab was defined as endoscopic and histologic healing at 4-6 weeks after first infliximab treatment. Six control patients with normal colonoscopy were included. Total RNA was isolated from colonic mucosal biopsies, labelled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Ingrid Arijs

PROVIDER: E-GEOD-14580 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis.

Arijs I I Li K K Toedter G G Quintens R R Van Lommel L L Van Steen K K Leemans P P De Hertogh G G Lemaire K K Ferrante M M Schnitzler F F Thorrez L L Ma K K Song X-Y R XY Marano C C Van Assche G G Vermeire S S Geboes K K Schuit F F Baribaud F F Rutgeerts P P

Gut 20090820 12

<h4>Background and aims</h4>Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNFalpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis.<h4>Methods</h4>Two cohorts of patients who received their first treatment with infliximab for re ...[more]

PMID: 19700435

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Project description:Background & Aims: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n=8), quiescent UC (n=9), and with irritable bowel syndrome (controls, n=10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P11 software (Umetrics, Umeå, Sweden). Results: A clear separation between active UC, quiescent UC and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC and control biopsies was governed by unique profiles containing gene expressions with significant fold changes. These primarily belonged to the family of homeostatic chemokines revealing a plausible explanation to the abnormal regulated innate immune response seen in patients with UC. Conclusion: This study has demonstrated the presence of a continuous inflammatory state in quiescent UC, which seems to reflect an altered gene expression profile of lamina propria cells. Keywords: Colonocytes, continuous inflammation, mucosal colonic biopsies, gene expression profiles Adjacent mucosal colonic biopsies were attained endoscopically from the descending colon in patients with active UC (n=8), quiescent UC (n=9), and in controls (n=10). After extraction of total RNA, genome-wide gene expression data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Amplification was required to obtain sufficient amounts of labelled complementary RNA (cRNA) target for analysis with arrays. Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P11 software (Umetrics, Umeå, Sweden).

Dataset Information

Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis

Publications

Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis.

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