Genome-wide DNA methylation profiling in rheumatoid arthritis identifies disease-associated methylation changes that are distinct to individual T- and B-lymphocyte populations

Glossop, John R; Emes, Richard D.; Nixon, Nicola B; Haworth, Kim E.; Packham, Jon; Dawes, P. T.; Fryer, Anthony A.; Mattey, Derek L.; Farrell, William E.

doi:10.4161/epi.29718

Cited by 85 publications

(61 citation statements)

References 59 publications

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“…In addition, candidate gene studies also describe aberrant methylation across multiple, discrete, genes in these cell types [12][13][14][15][16][17][18]. Further to these studies, and in this case using genome-wide methylation arrays, we recently reported disease-associated methylation changes in multiple genes that were distinct to individual T-and B-lymphocyte populations [19]. Similar findings in the context of alterations to the epigenome are also 5 apparent in fibroblast-like synoviocytes derived from the joint [20][21][22][23][24][25][26][27], which further supports an important role for altered methylation in the pathogenesis of RA.…”

Section: Introductionmentioning

confidence: 92%

“…Genome-wide DNA methylation was investigated in 23 Caucasian patients recruited consecutively from the early synovitis clinic at the Haywood Rheumatology Centre in Stoke-on-Trent, UK, and also in a group of 11 healthy Caucasian females, the details of which we have previously reported [19]. All patients had symptomatic inflammatory arthritis suspected to be RA at presentation, and subsequently were classified with RA by a consultant rheumatologist and according to the 2010 ACR/EULAR classification criteria [31].…”

Section: Patientsmentioning

confidence: 99%

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Genome-Wide Profiling in Treatment-Naive Early Rheumatoid Arthritis Reveals DNA Methylome Changes in T and B Lymphocytes

et al. 2015

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Section: Introductionmentioning

confidence: 92%

Section: Patientsmentioning

confidence: 99%

Genome-Wide Profiling in Treatment-Naive Early Rheumatoid Arthritis Reveals DNA Methylome Changes in T and B Lymphocytes

et al. 2015

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“…NIMBL was used to perform 'peak-based' correction, to adjust for potential differences in array probe-type sensitivity previously reported 33 ; all comparative analyses of high-grade tumors to normal bladder controls, were performed on peak-based corrected b-values, as described by us previously. 68 Each array passed quality control assessment based upon the performance of internal controls and the distribution of b-values across all array CpGs. As previously described, 68 and represented by step 1 of Fig.…”

Section: Illumina Humanmethylation450 Beadchip Array Analysesmentioning

confidence: 99%

“…68 Each array passed quality control assessment based upon the performance of internal controls and the distribution of b-values across all array CpGs. As previously described, 68 and represented by step 1 of Fig. 1, we excluded all CpGs for which any of the 24 samples displayed: (i) probe detection P-values >0.05 (unreliable probe data), or (ii) missing b-values (preventing analyses of all samples).…”

Section: Illumina Humanmethylation450 Beadchip Array Analysesmentioning

confidence: 99%

“…Arrays were processed according to the manufacturer's instructions (performed by Barts and the London Genome Center, UK), as described by us previously. 66 Raw array data were processed using GenomeStudio software and the bioinformatical platform 'NIMBL', as we 67,68 and others 69 have described. For each probe, the methylation status was reported as a methylation 'b-value', where 'b' is defined as the ratio of the methylated signal intensity over the summed intensity of the methylated and unmethylated signals C 100.…”

Section: Illumina Humanmethylation450 Beadchip Array Analysesmentioning

confidence: 99%

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936 Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer

Kitchen¹,

Bryan²,

Emes³

et al. 2016

European Urology Supplements

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High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to lowintermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease.

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Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells

Boyle

Wang

et al. 2021

ACR Open Rheumatology

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Objective To study epigenetic patterns in T lymphocytes that accumulate in the rheumatoid arthritis (RA) synovium, we characterized DNA methylation of CD3+ T cells in peripheral blood and synovial tissue in patients with RA and osteoarthritis (OA). Methods Genomic DNA of CD3+ T cells was isolated from patients with RA (n = 8) and OA (n = 5) from blood or the synovium at the time of an arthroplasty using antibodies and magnetic beads. Methylation was measured by using the Illumina Infinium MethylationEPIC Kit. Differentially methylated loci (DML) and differentially methylated genes (DMGs) were identified by using Welch’s t‐test. Principal component analysis, hierarchical clustering, and pathway analysis were used to determine relationships among groups. Results When we compared DNA methylation of CD3+ T cells between peripheral blood and synovial tissue within each disease, 4615 and 164 DML were identified in RA and OA samples, respectively, resulting in 832 and 36 DMGs. A principal component analysis showed that methylation differences in T cells were greater on the basis of on location (blood vs synovium) rather than disease (RA vs OA). Differentially modified pathways were significantly enriched between RA blood and synovial T cells, especially in genes related to complement, integrin cell surface interactions, and the P53 pathway. The limited number of DMGs identified between OA blood and synovial T cells did not conform to biologic pathways. Conclusion The patterns of DNA methylation in RA show location‐specific differences related to immune pathways, whereas methylation differences in OA are limited. The RA joint‐specific signatures could be due to selective accumulation of T‐cell populations or expansion of differentially marked adaptive immune cells. Understanding epigenetic patterns could provide clues to the types of T cells that accumulate in the RA joint and identify potential therapeutic targets.

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Genome-wide DNA methylation profiling in rheumatoid arthritis identifies disease-associated methylation changes that are distinct to individual T- and B-lymphocyte populations

Cited by 85 publications

References 59 publications

Genome-Wide Profiling in Treatment-Naive Early Rheumatoid Arthritis Reveals DNA Methylome Changes in T and B Lymphocytes

Genome-Wide Profiling in Treatment-Naive Early Rheumatoid Arthritis Reveals DNA Methylome Changes in T and B Lymphocytes

936 Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer

Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells

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