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Distinct, non-overlapping gene panels of peripheral blood gene expression predict response to infliximab therapy in rheumatoid arthritis and Crohn's disease

ABSTRACT: We used microarrays to identify markers predicting responder status in infliximab treatment in 19 rheumatoid arthritis and 20 Crohn's disease patients at week 0 and week 2 of treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42296 | GEO | 2013/06/25

SECONDARY ACCESSION(S): PRJNA179561

REPOSITORIES: GEO

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Distinct, non-overlapping gene panels of peripheral blood gene expression predict response to infliximab therapy in rheumatoid arthritis and Crohn's disease

Project description:We used microarrays to identify markers predicting responder status in infliximab treatment in 19 rheumatoid arthritis and 20 Crohn's disease patients at week 0 and week 2 of treatment. Peripheral blood samples were obtained at week 0 and week 2 of inxliximab treatment and global gene expression profiling identified markers of responder status.

2013-06-25 | E-GEOD-42296 | biostudies-arrayexpress

Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease.

Project description:BackgroundBiological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided.MethodWe addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline.ResultsGene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions.ConclusionsOur data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process.

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PBMC gene expression from Crohn's disease patients before Infliximab therapy.

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

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.

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Expression data from colonic biopsy samples of infliximab treated UC patients

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Microarray predictor of response to infliximab in rheumatoid arthritis (RA) patients

Project description:We sought to find a gene-expression multigene predictor of response to infliximab therapy in Rheumatoid Arthritis patients. Using internal and external cross-validation systems we have built and validated an 8-gene predictor for response to infliximab.

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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.

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Expression data from colonic biopsy samples of infliximab treated ulcerative colitis patients

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Expression profiling of responsiveness to infliximab in rheumatoid arthritis patients

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