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.
Project description:Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. In this study, we sought to identify a blood gene expression biomarker correlating with 12-week response to infliximab in patients with moderate to severe disease. Response was assessed using dynamic contrast-enhanced MRI imaging of the wrist. Baseline whole blood samples from 59 patients were collected as part of a placebo-controlled clinical study of infliximab in rheumatoid arthritis. Samples were profiled by Affymetrix microarray and correlation between gene expression and 12-week response was assessed. DAS28 (Disease Activity Score including a 28-joint count)
Project description:Identifying gene expression profiles as predictors of a good vs poor response to a combined infliximab/methotrexate treatment in rheumatoid arthritis patients. Keywords: drug response
Project description:objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment.
Project description:objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment
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:TNF antagonists are routinely used in severe rheumatoid arthritis (RA) patients who failed conventional DMARD therapy. According to large clinical trials, the three available drugs (adalimumab, infliximab and etanercept) display similar effects in terms of efficacy, tolerability and side effects. These studies also indicate that about 25% of RA patients treated with TNF-antagonists do not display any significant clinical improvement. The aim of this study was to investigate global molecular patterns in synovial biopsies from RA patients obtained 12 weeks after initiation of adalimumab therapy.
Project description:In order to identify new biomarkers for the diagnosis of rheumatoid arthritis, we used circRNA microarray technology to screen the differential expression of circRNA in peripheral blood mononuclear cells of patients with rheumatoid arthritis. We identified a total of 399 differentially expressed circRNAs in RA patients and healthy controls, of which 149 circRNAs were significantly up-regulated in RA patients and 250 were down-regulated. Among them, hsa_circRNA_101328 may be a potential biomarker for the diagnosis of RA.
Project description:Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. In this study, we sought to identify a blood gene expression biomarker correlating with 12-week response to infliximab in patients with moderate to severe disease. Response was assessed using dynamic contrast-enhanced MRI imaging of the wrist.