Project description:With a focus on rheumatoid arthritis (RA), we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritise molecular pathways for targeting in this and related immune pathologies. Whole genome methylation data from isolated B cells of >100 genotyped and phenotyped inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with GWAS findings across IMDs and other publically available resources.
Project description:With a focus on rheumatoid arthritis (RA), we sought new insight into genetic mechanisms of adaptive immune dysregulation to help prioritise molecular pathways for targeting in this and related immune pathologies. Whole genome methylation data from isolated CD4+ T cells of >100 genotyped and phenotyped inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments, were obtained. Analysis integrated these comprehensive data with GWAS findings across IMDs and other publically available resources.
Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls Bisulphite converted DNA from the Rheumatoid arthritis patients (cases) and normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays
Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in peripheral blood leukocytes (PBLs). We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls
Project description:Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints involved with genetic and epigenetic aberrant. Recent evidence found more and more importance of the epigenetic contribution, especially the DNA methylation, to the pathogenesis of rheumatoid arthritis. To understand the extent and nature of dysregulated DNA methylation in rheumatoid arthritis T cells, we performed a genome-wide DNA methylation study in CD4+ T cells in 12 rheumatoid arthritis patients compared to 12 matched normal healthy controls. [Methods and Result] Cytosine methylation status was quantified with Illumina methylation 450K microarray (HM450K, 485512 CpG sites). We identified 810 hypomethylated and 392 hypermethylated CG sites in RA CD4+ T cells compared to normal controls, representing 383 and 785 genes hypermethylated and hypomethylated in RA patients (P<3.4*10-7). Cluster analysis based on significantly differential methylated loci showed distinct separation between RA and normal controls. Gene ontology analysis showed alternative splicing (P=1.2*10-7, FDR) and phosphoprotein (1.7*10-2, FDR) were significantly aberrant in RA patients, indicating the abnormal of transcript alternative splicing and protein modification mediated by DNA methylation might play important role in the pathogenesis of rheumatoid arthritis. What’s more, the result showed human leukocyte antigen (HLA) region was frequently hypomethylated in RA patients, including HLA-DRB6, HLA-DQA1 and HLA-E, however, HLA-DQB1 showed different methylation profiles with significant hypermethylation in CpG island region and hypomethylation in CpG shelf region. Outsite of the MHC region, the most hypermethylated genes in RA included HDAC4, NXN, TBCD and TMEM61 while the most significant hypomethylated genes included ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9. [Conclusion] Genome-wide DNA methylation patterns revealed significant DNA methylation change in CD4+ T cells from patients with rheumatoid arthritis. 12 rheumatoid arthritis and 12 matched health individuals
Project description:242 patients recruited from an early arthritis clinic donated RNA and DNA from freshly isolated and purified peripheral blood CD19+ B cells. Global gene expression measurement was carried out using Illumina BeadChip HT12v4 microarrays. Objectives included the identification of B cell transcripts differentially expressed between disease phenotypes, where all patients were naive to immunomodulatory therapy. In addition an eQTL analysis was carried out with reference to known genotype data for this cohort of patients
Project description:The identification of predictive markers in an early undifferentiated arthritis (UA) patients is pivotal for selecting appropriate therapies to avoid a poor prognosis. In this work, we investigated the association between clinical features and DNA methylation patterns in monocytes from UA patients to seek potential prognostic biomarkers.
Project description:Genome wide DNA methylation profiling of rheumatoid arthritis (RA) patients and healthy controls. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles in peripheral blood mononuclear cells (PBMCs). Samples included 25 RA patients and 18 healthy controls.
Project description:Undifferentiated arthritis (UA) is the term used to cover all the cases of arthritis that do not fit a specific diagnosis. A high proportion of UA patients can progress to rheumatoid arthritis (RA) or a different definite rheumatic disease, while others undergo spontaneous remission. In this study, we performed DNA methylation profiling of a UA cohort, in which progression into RA occurs for a significant proportion of the patients.