Early arthritis CD4+ T cell DNA methylation profiling
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ABSTRACT:
PROVIDER: PRJNA565981 | ENA |
REPOSITORIES: ENA
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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.
2019-12-17 | GSE137593 | GEO
Project description:Early arthritis B cell DNA methylation profiling
| PRJNA565982 | ENA
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
2017-07-29 | GSE71841 | GEO
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.
2019-12-17 | GSE137594 | GEO
Project description:An exploration of the peripheral blood CD4+ T-cell transcriptome of early arthritis clinic attendees, seeking novel diagnostic tools and pathophysiological insights. Ex-vivo CD4+ T-cell RNA was obtained following first early arthritis clinic attendance from 173 patients. Four diagnostic categories were confirmed at median 28 months follow-up. Outcome categories are ACPA- RA (A; n=31), ACPA+ RA (B; n=41), Non-RA Inflammatory arthritis (C; n=56), and Non-RA/Non-Inflammatory arthritis (D; n=45). In order to derive and validate a diagnostic gene signature, samples were split into Training set (where patients could be diagnosed at presentation; n=111) and validation set of undifferentiated arthritis (UA; n=62) patients, in whom diagnosis could only be confirmed after the follow-up period. Arrays were processed in two phases (phases 1 and 2). Phase 1 was split into 4 labelling batches, Phase 2 was split into 2 labelling batches. Batch effects were controlled for using this information using the empirical Bayes approach of Johnson et al. (2007). The supplementary file 'GSE20098_non-normalized.txt' contains non-normalized data for Samples GSM502124-GSM502280 and GSM506251-GSM506266.
2012-03-03 | E-GEOD-20098 | biostudies-arrayexpress
Project description:An exploration of the peripheral blood CD4+ T-cell transcriptome of early arthritis clinic attendees, seeking novel diagnostic tools and pathophysiological insights.
2012-03-03 | GSE20098 | GEO
Project description:The genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation and many T-cells genes with a strong MHC-association, pointing to immuno-genetic mechanisms as disease triggers. We aim to identify methylation change in naive and memory CD4+T-cells and monocytes in the early stage of disease, to gain insight to disease pathology. DNA-methylation was explored using a genome wide array (DNA methylation Illumina 450K bead chip array). Differential methylation in promoters of many genes was associated with several disease relevant pathways notably in naive CD4+T-cells. This pointed to the IL6/JAK1/STAT3 signalling cascade linking into inflammatory mechanisms and TNF signalling as well as the engagement of naive CD4 T-cells intoTh17 differentiation and the implication of several Interferon response genes.
2020-04-20 | GSE121192 | GEO
Project description:An exploration of the peripheral blood CD4+ T-cell transcriptome of early arthritis clinic attendees, (i) to provide validation of previously published observations, and (ii) to facilitate an eQTL analysis.
2018-04-03 | GSE80513 | GEO
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
2013-01-21 | E-GEOD-42861 | biostudies-arrayexpress
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
2013-01-21 | GSE42861 | GEO