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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\u2010reactive protein level were collected at baseline and after 3\u20136 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\u2010specific differential DNAm at the CpG level from tissue\u2010level (\u201cbulk\u201d) data. Differentially methylated regions were identified using Comb\u2010p software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell\u2010specific 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\u2010nine cell\u2010specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified cell\u2010specific 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.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42464-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42464","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T11:45:27Z","timestamp":1675079127000},"page":"1088-1097","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Identification of\n                    <scp>Cell\u2010Specific<\/scp>\n                    Differential\n                    <scp>DNA<\/scp>\n                    Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2525-523X","authenticated-orcid":false,"given":"Cameron","family":"Adams","sequence":"first","affiliation":[{"name":"School of Public Health, University of California  Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Nair","sequence":"additional","affiliation":[{"name":"Centre of Genetics and Genomics Versus Arthritis, Manchester Academic Health Sciences Centre, The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Plant","sequence":"additional","affiliation":[{"name":"Centre of Genetics and Genomics Versus Arthritis, Manchester Academic Health Sciences Centre, NIHR Manchester BRC, Manchester University Foundation Trust, The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M. M.","family":"Verstappen","sequence":"additional","affiliation":[{"name":"NIHR Manchester BRC, Manchester University Foundation Trust, and Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK, Institute of Cellular Medicine, Newcastle University, and NIHR Newcastle BRC, Newcastle upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong L.","family":"Quach","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California  Berkeley"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana L.","family":"Quach","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California  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