{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:09:22Z","timestamp":1789556962603,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI097134"],"award-info":[{"award-number":["R01 AI097134"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, with childhood\u2010onset SLE (cSLE) typically presenting a more severe course and greater genetic risk than adult\u2010onset SLE. Although DNA methylation plays a key role in lupus pathogenesis, the epigenetic landscape of cSLE remains understudied. This study aimed to investigate DNA methylation changes in cSLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 64 patients with cSLE and 47 healthy control DNA samples isolated from peripheral blood mononuclear cells (PBMCs), along with an independent validation cohort of 38 patient DNA samples from whole blood, were analyzed. DNA methylation was assessed using the Infinium MethylationEPIC version 2.0 array. Methylation differences were tested via linear regression adjusting for age, sex, medication use, and cell composition. Clinical features were compared using the chi\u2010square test or Fisher's exact test, and Gene Ontology enrichment was conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Differential methylation analysis revealed significant hypomethylation in interferon\u2010regulated genes (eg,\n                      <jats:italic>DTX3L<\/jats:italic>\n                      ,\n                      <jats:italic>PARP9<\/jats:italic>\n                      ,\n                      <jats:italic>IFI44L<\/jats:italic>\n                      ,\n                      <jats:italic>MX1<\/jats:italic>\n                      ), enriched in type I interferon\u2013related processes. Hypomethylation in genes linked to B cell activation and senescence correlated with higher SLE Disease Activity Index scores. K\u2010means clustering identified three distinct methylation\u2010based cSLE subgroups, each enriched for different biologic processes: cell adhesion and growth factor response (cluster 1), cell differentiation and fate (cluster 2), and oxidative stress and Ras\u2010associated protein\u20101 signaling (cluster 3). Sex\u2010based analysis showed immune\u2010related hypomethylation in male patients, with almost 90% of these sites identified in PBMCs also replicating in an independent whole blood dataset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>cSLE displays distinct DNA methylation patterns associated with disease activity, molecular subgroups, and sex, underscoring the potential for epigenetically informed diagnostics and therapies.<\/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\/art70045-gra-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.70045","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T10:00:12Z","timestamp":1766743212000},"page":"1245-1257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>DNA<\/scp>\n                    Methylation Profiling Reveals Distinct Epigenetic Clusters and Suggests Epigenetic Patterns Associated With Sex and Disease Activity in Childhood\u2010Onset Lupus"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4928-3545","authenticated-orcid":false,"given":"Desir\u00e9","family":"Casares\u2010Marfil","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Pediatrics University of Pittsburgh  Pittsburgh 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