Project description:At a given time, rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms is still poorly understood. Because previous microarrays studies have only focused on late RA stages, we aimed to compare the biological and molecular profiles in early and long-standing (LS) RA. Synovial biopsies obtained by arthroscopy were performed in 4 early untreated RA patients, 4 LS treated RA patients and 7 control patients. Extracted mRNA were linearly amplified and used for large-scale gene expression profiling by cDNA arrays. By gene ontology analysis, the different gene combinations obtained by comparison of early, LS RA and normal synovium were used to identify the biological processes, molecular functions and pathways involved at each stage. Three combinations of 719, 116 and 52 transcripts dissociated respectively early from LS RA patients, early or LS RA from normal synovium. We identified several gene clusters and distinct molecular signatures specifically related to early or LS RA suggesting the involvement of different pathological mechanisms at each stage. Early and LS RA have distinct molecular signatures with the participation of different biological processes during the course of the disease. These results suggest that a better knowledge of the main biological processes involved at a given RA stage might help the rheumatologist to choose the more appropriate treatment. PBMC then RNA were extracted from synovial biopsies of 4 eraly RA patients, 4 long-standing RA patients and from 7 normal synovium used as control. Each sample was hybridized three times in different nylon membrane.
Project description:At a given time, rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms is still poorly understood. Because previous microarrays studies have only focused on late RA stages, we aimed to compare the biological and molecular profiles in early and long-standing (LS) RA. Synovial biopsies obtained by arthroscopy were performed in 4 early untreated RA patients, 4 LS treated RA patients and 7 control patients. Extracted mRNA were linearly amplified and used for large-scale gene expression profiling by cDNA arrays. By gene ontology analysis, the different gene combinations obtained by comparison of early, LS RA and normal synovium were used to identify the biological processes, molecular functions and pathways involved at each stage. Three combinations of 719, 116 and 52 transcripts dissociated respectively early from LS RA patients, early or LS RA from normal synovium. We identified several gene clusters and distinct molecular signatures specifically related to early or LS RA suggesting the involvement of different pathological mechanisms at each stage. Early and LS RA have distinct molecular signatures with the participation of different biological processes during the course of the disease. These results suggest that a better knowledge of the main biological processes involved at a given RA stage might help the rheumatologist to choose the more appropriate treatment.
Project description:We report the first comparative analysis between histology, RNA-seq of synovium and matched peripheral blood, and clinico-radiological parameters in early rheumatoid arthritis (RA). Using a novel modular approach, we describe underlying pathways associated with three pre-dominant RA pathotypes. Myeloid was associated with macrophages, lymphoid with B and plasma cells, and fibroid with minimal inflammatory cell infiltration. Synovium RNA-seq was better correlated with the pathotypes than blood RNA-seq, but peripheral blood signatures, including type I interferon, were detected as associated with particular myeloid or lymphoid pathotypes. This study describes the molecular heterogeneity of RA and provides major new insights into the cross compartmental molecular pathways that underlie RA.
Project description:Transcriptional profiling of human synovial tissue from thirteen individuals with arthralgia who were IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive and without any evidence of arthritis. Survival analysis was used to identify transcripts associated with arthritis after follow up. This study was performed to investigate the molecular changes in synovium preceding arthritis development in at risk individuals.
Project description:Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive arthritis. Although helper T cells are involved in the pathogenesis of RA, the characteristics of synovium-infiltrating CD4+ T cells are still largely unknown. In this study, we investigated synovium-infiltrating helper T cells of rheumatoid arthritis patients
Project description:Intent of this experiment is to define the baseline transcriptome of the synovium obtained from rheumatoid arthritis patients prior to initiation of DMARD (Disease-modifying antirheumatic drug) therapy and compare it with the synovial transcriptome of rheumatoid arthritis patients with an established disease profile.
Project description:Rheumatoid arthritis is an autoimmune inflammatory joint condition which primarily affects the synovium of joints, characterised by synovial inflammation as well as articular cartilage and underlying bone destruction. Within this study, the proteomes of serum obtained from rheumatoid arthritis patients, and appropriate human controls, were analysed using liquid chromatography-tandem mass spectrometry. ProteoMiner™ equalisation columns were used to deplete high abundant proteins and reduce the protein concentration dynamic range.
Project description:To find regulated miRNAs during peak inflammation of rheumatoid arthritis (RA), we have collected synovium from mouse STA model at day 0 (Non Arthritic) and day 10 (Peak Inflammation). For miRNA profiling, we used high-throughput BioMark Real-Time PCR system (Fluidigm, South San Francisco, CA)
