Project description:Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Using regression correlation
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 (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract. Keywords: all_pairs
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:Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria.
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:Osteoarthritis (OA) causes pain and functional disability for over 500 million people worldwide and is characterized by progressive loss of cartilage and synovial hyperplasia from the articulating surfaces of diarthrodial joints. Although the etiology of the disease is unknown, it is widely accepted that these degenerative changes arise from an imbalance of synthetic and degradative pathways that control cartilage and synovium extracellular matrix metabolism. Genome-wide U133A Affymetrix oligonucleotide array set was used to comprehensively investigate the expression pattern in non-osteoarthritis (normal) and synovium obtained from OA and rheumatoid arthritis (RA) patients undergoing knee replacement surgery. This study was undertaken to understand the disease's molecular basis better and provide relevant insight into phenotypical alterations and mechanisms involved in OA pathogenesis.
Project description:Synovial biopsies were obtained from rheumatoid arthritis (RA) synovium and from subjects without a joint disease to find gene upregulated during RA. The promoters of genes upregulated during RA compared to HC can be used to obtain disease-regulated gene therapy.
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: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)