Mucosal Gene Expression Defects in IBD

Inflammatory Bowel Diseases

Gene expression microarray, Inflammatory bowel disease, Infliximab

This study investigated the mucosal gene expression defects associated with active Crohn's disease (CD)and ulcerative colitis (UC), and studied the effect of infliximab induced downregulation of inflammation and mucosal healing on these abnormalities, using whole genome gene expression microarrays.

Infliximab, a monoclonal IgG1 antibody to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), was the first efficacious biological therapy for IBD. Infliximab dramatically improved the quality of life in IBD patients. Besides inducing and maintaining remission in refractory IBD patients, infliximab has achieved new treatment goals such as intestinal mucosal healing and a reduction in hospitalizations and surgeries on the long-term. However, up to 30% of IBD patients do not respond to this costly therapy and potentially harmful therapy, and in an extra 20-30% response is incomplete. The mechanism of resistance to infliximab is unknown and predictors of response to infliximab are currently lacking. The aim of this study was to investigate the mucosal gene expression defects associated with active Crohn's disease (CD)and ulcerative colitis (UC), and to study the effect of infliximab induced downregulation of inflammation and mucosal healing on these abnormalities, using whole genome gene expression microarray technology on endoscopic-derived intestinal mucosal biopsies from control individuals and patients with active IBD, and this before and after their first infliximab treatment. Sixty-one patients with inflammatory bowel disease, 19 with Crohn's colitis, 18 with Crohn's ileitis and 24 with UC, undergo a colonoscopy with biopsies before and 4-6 weeks after the first infliximab treatment. Response to infliximab was defined based on endoscopic and histologic findings. A control group of 12 individuals was also included.Total RNA was isolated from biopsies, labelled and hybridized to Affymetrix HGU133plus2.0 Array. Microarray data were analyzed using Bioconductor software and Ingenuity Pathway Analysis software. Quantitative real time RT-PCR and immunohistochemistry were used to confirm microarray data.

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Belgium