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| Status |
Public on Feb 01, 2021 |
| Title |
Distinct DNA methylation patterns of rheumatoid arthritis peripheral blood and synovial tissue T cells |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Objective: To study epigenetic patterns in T lymphocytes that accumulate in rheumatoid arthritis (RA) synovium, we characterized DNA methylation of CD3+ T cells in peripheral blood and synovial tissue in RA and osteoarthritis (OA) patients.
Methods: Genomic DNA of CD3+ T cells was isolated from RA (n = 8) and OA (n = 5) patients from blood or synovium at the time of arthroplasty using antibodies and magnetic beads. Methylation was measured using Illumina Infinium MethylationEPIC Kit. Differentially methylated loci (DMLs) and genes (DMGs) were identified using Welch’s t-test. Principal component analysis (PCA), hierarchical clustering and pathway analysis were used to determine relationships among groups.
Results: Comparing DNA methylation of CD3+ T cells between peripheral blood and synovial tissue within each disease, 4615 and 164 DMLs were identified in RA and OA samples respectively, resulting in 832 and 36 DMGs. PCA showed that methylation differences in T cells were greater based on location (blood vs. synovium) than based on 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 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, while 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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| Overall design |
Bisulphite converted DNA from the 22 samples were hybridised to the Illumina Infinium MethylationEPIC Kit chip
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| Contributor(s) |
Ai R, Boyle DL, Wang W, Firestein GS |
| Citation(s) |
33544432 |
| Submission date |
Jan 08, 2021 |
| Last update date |
May 03, 2021 |
| Contact name |
Gary S Firestein |
| E-mail(s) |
gfirestein@ucsd.edu
|
| Organization name |
UCSD
|
| Street address |
9500 Gilman Dr
|
| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA690798 |
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