Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
13
01
2023
received:
22
07
2022
accepted:
26
01
2023
pmc-release:
01
07
2024
medline:
29
6
2023
pubmed:
31
1
2023
entrez:
30
1
2023
Statut:
ppublish
Résumé
We undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment. Patients included in this study were from the Rheumatoid Arthritis Medication Study (n = 66) and the University of California San Francisco Rheumatoid Arthritis study (n = 11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software. We found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples. We identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.
Identifiants
pubmed: 36716083
doi: 10.1002/art.42464
pmc: PMC10313739
mid: NIHMS1869550
doi:
Substances chimiques
Methotrexate
YL5FZ2Y5U1
Antirheumatic Agents
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1088-1097Subventions
Organisme : NINDS NIH HHS
ID : F31 NS113537
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070155
Pays : United States
Organisme : NINDS NIH HHS
ID : 1F31NS113537-01A1
Pays : United States
Informations de copyright
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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