Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells
ObjectiveTo 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).MethodsGenomic DNA of CD3+ T cells was isolated from...
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ftcdlib:oai:escholarship.org:ark:/13030/qt1zg468cw 2023-09-05T13:19:06+02:00 Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells Ai, Rizi Boyle, David L Wang, Wei Firestein, Gary S 127 - 132 2021-03-01 application/pdf https://escholarship.org/uc/item/1zg468cw unknown eScholarship, University of California qt1zg468cw https://escholarship.org/uc/item/1zg468cw public ACR Open Rheumatology, vol 3, iss 3 Human Genome Genetics Clinical Research Autoimmune Disease Rheumatoid Arthritis Arthritis Aging Aetiology 2.1 Biological and endogenous factors Inflammatory and immune system article 2021 ftcdlib 2023-08-21T18:06:16Z ObjectiveTo 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).MethodsGenomic 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.ResultsWhen 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.ConclusionThe 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. Article in Journal/Newspaper DML University of California: eScholarship |
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University of California: eScholarship |
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unknown |
topic |
Human Genome Genetics Clinical Research Autoimmune Disease Rheumatoid Arthritis Arthritis Aging Aetiology 2.1 Biological and endogenous factors Inflammatory and immune system |
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Human Genome Genetics Clinical Research Autoimmune Disease Rheumatoid Arthritis Arthritis Aging Aetiology 2.1 Biological and endogenous factors Inflammatory and immune system Ai, Rizi Boyle, David L Wang, Wei Firestein, Gary S Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells |
topic_facet |
Human Genome Genetics Clinical Research Autoimmune Disease Rheumatoid Arthritis Arthritis Aging Aetiology 2.1 Biological and endogenous factors Inflammatory and immune system |
description |
ObjectiveTo 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).MethodsGenomic 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.ResultsWhen 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.ConclusionThe 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. |
format |
Article in Journal/Newspaper |
author |
Ai, Rizi Boyle, David L Wang, Wei Firestein, Gary S |
author_facet |
Ai, Rizi Boyle, David L Wang, Wei Firestein, Gary S |
author_sort |
Ai, Rizi |
title |
Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells |
title_short |
Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells |
title_full |
Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells |
title_fullStr |
Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells |
title_full_unstemmed |
Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells |
title_sort |
distinct dna methylation patterns of rheumatoid arthritis peripheral blood and synovial tissue t cells |
publisher |
eScholarship, University of California |
publishDate |
2021 |
url |
https://escholarship.org/uc/item/1zg468cw |
op_coverage |
127 - 132 |
genre |
DML |
genre_facet |
DML |
op_source |
ACR Open Rheumatology, vol 3, iss 3 |
op_relation |
qt1zg468cw https://escholarship.org/uc/item/1zg468cw |
op_rights |
public |
_version_ |
1776199917852688384 |