Project description:We used microarrays to identify mucosal gene signatures predictive of response to infliximab (IFX) in patients with inflammatory bowel disease (IBD) and to gain more insight into the pathogenesis of IBD. Keywords: drug response and treatment effect Mucosal biopsies were obtained at endoscopy in actively inflamed mucosa from 61 IBD patients (24 ulcerative colitis (UC), 19 Crohnâs colitis (CDc) and 18 Crohnâs ileitis (CDi)), refractory to corticosteroids and/or immunosuppression, before and 4-6 weeks after (except for 1 CDc patient) their first infliximab infusion and in normal mucosa from 12 control patients (6 colon and 6 ileum). The patients were classified for response to infliximab based on endoscopic and histologic findings at 4-6 weeks after first infliximab treatment. Total RNA was isolated from intestinal mucosal biopsies, labelled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.
Project description:We used microarrays to identify mucosal gene signatures predictive of response to infliximab (IFX) in patients with inflammatory bowel disease (IBD) and to gain more insight into the pathogenesis of IBD. Keywords: drug response and treatment effect
Project description:To further explore predictors and targets of response to infliximab, differential gene expression was examined at baseline and after 6 and 24 hours and 2 weeks after the first infusion of infliximab in TRD patients who were infliximab responders versus nonresponders, and compared to placebo-treated patients. All subjects were administered either infliximab (5mg/kg, n=30) or placebo (n=30) through an indwelling catheter at the Emory Division of Digestive Diseases at 3 separate time points (baseline, 2 weeks and 6 weeks). Infliximab infusion dosing protocol and scheduling were matched to the standard intravenous induction routine for the treatment of inflammatory bowel disease.
Project description: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.
Project description:This study focuses on inflammatory bowel disease gene expression profiling. Surgical specimens from 134 patients undergoing bowel resection for inflammatory bowel disease (IBD) and non IBD controls at Mount Sinai Medical Center were collected as the source of tissue. Control samples (CLs) were harvested from normal non inflamed bowel located more than 10 cm away from the tumor from patients undergoing bowel resection for sporadic colon cancer. Ulcerative colitis (UC) and Crohn’s (CD) patient samples were all isolated from areas containing moderate to severe inflammation. The diagnostic pathology report for each specimen was provided by the Mount Sinai Hospital Pathology Department. Patients with UC and patients with CD shared common medications including corticosteroids, infliximab, azathioprine, and mesalamine.
Project description:Crohn’s disease (CD) and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of which the etiology and pathogenesis are not completely understood. In paediatric patients, the disease tends to be more severe and aggressive then in adults. Here, we perform a proteomic approach on ascending colon biopsies from 119 pediatric patients to characterize disease pathogenesis and the impacts of treatment. Consistent with previous findings, we report an altered proteome in IBD patients that indicates impaired mitochondrial function. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of proteomes from CD patients before and after therapeutic intervention identified over 100 proteins that are significantly different between patients that responded and those that did not respond to therapy; creatine kinase B was elevated before treatment in patients with mucosal healing after treatment, whereas basigin increased after treatment in responsive patients.
Project description:Objectives: We monitored the mRNA expression profiles of peripheral blood cells during treatment with a tumor necrosis factor-a inhibitor, infliximab, in patients with rheumatoid arthritis (RA). Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.Methods: Using a customized low-density cDNA microarray and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the American College of Rheumatology (ACR) response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results: Approximately 15% of the total genes were found to exhibit a greater than 1.5-fold change, compared to their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as interferon-related genes, was strongly correlated with the serum level of C-reactive protein and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.Conclusions: Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. Keywords: disease state analysis 18 RA Patients, We have collected blood samples into PAXgene tube systems for microarray measurement from patients as follows, just before first iv-injection of infliximab, 2 weeks, 14 weeks, and 22 weeks after first infliximab injection.
Project description:Colonic aspirates were collected at diagnostic colonoscopy from inflammatory bowel disease (IBD) and control, treatment-naive children. The colonic mucosal-luminal interface (MLI) proteomes were analyzed for 18 control and 42 IBD patients by liquid-chromatography mass spectrometry.