Project description:Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy.
Project description:Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy. Methods: We performed a microarray assay of the whole human genome with RNA from a peripheral blood sample taken before the first RTX cycle from 68 patients included in the SMART study (24 EULAR non-responders and 44 responders at week 24). The transcriptomic profile was also assessed 24 weeks after the first RTX administration
Project description:New and effective therapeutical options are available for the treatment of Rheumatoid Arthritis. One of such treatments is rituximab, and chimeric anti-CD20 antibody that selectively depletes the CD20+ B cell subpopulation. Similar to established anti-TNF alpha therapies, there is a subgroup of RA patients that do not experience significant clinical response. Therefore, one of the major necessities in actual RA therapeutical management is to identify reliable predictors of the response to this therapies. In the present study we have evaluated 3 blood cell types (i.e. whole blood, isolated B cells and isolated CD4 T cells) using microarray gene expression profiling to identify their potential use as biomarkers for rituximab response. In all three tissues evaluated, we have identified statistically significant differentially expressed genes. The most relevant candidates have been reevaluated using RealTime PCR. These genes were: TRAF1 and arginase 1 in whole blood, Toll-Like Receptor 4 (TLR4) in CD4+ T cells and AT-rich interactive domain 3A (ARID3A) in B cells. In the present study we have demonstrated the potential of different blood cell types for the prediction of the response to rituximab. In particular, we have found a set of relevant candidate genes that could be the basis for future treatment response prediction.
Project description:Transcriptomic profiles of synovial biopsies of rheumatoid arthritis (RA) patients who were recruited into the R4RA randomised clinical trial. Patients were randomised to treatment with rituximab or tocilizumab. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA and were eligible for treatment with rituximab therapy according to UK NICE guidelines, i.e. failing or intolerant to csDMARD therapy and at least one biologic therapy (excluding trial IMPs) were recruited when fulfilling the trial inclusion/exclusion criteria. For the full study protocol and baseline patient characteristics see Humby et al (2021) The Lancet 397(10271): 305-17. PMID: 33485455.
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:<p>Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p>
Project description:Our goal was to find correlations between gene expression patterns and impaired vascular pathophysiolgy in rheumatoid arthritis Patients with rheumatoid arthritis were recruited and venous blood samples were collected, then peripheral blood mononuclear cells were separated. After RNA isoltaion, we used Affymetrix PrimeView arrays to obtain whole gene expression data.