{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:03:15Z","timestamp":1784595795389,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007857","name":"Stiftelsen Konung Gustaf V:s 80-\u00e5rsfond","doi-asserted-by":"publisher","award":["FAI\u20102023\u20101052"],"award-info":[{"award-number":["FAI\u20102023\u20101052"]}],"id":[{"id":"10.13039\/501100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","award":["R\u2010995511"],"award-info":[{"award-number":["R\u2010995511"]}],"id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"abstract":"\n Objective<\/jats:title>\n Primary Sj\u00f6gren's disease (SjD) is a systemic autoimmune disease associated with an increased risk of lymphoma. The molecular mechanisms underlying lymphomagenesis remain poorly understood, and sensitive biomarkers for early identification of patients at high risk of developing lymphoma are lacking. This study investigated whether DNA methylation patterns in blood are associated with subsequent development of lymphoma in patients with SjD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Peripheral blood DNA samples collected from patients with SjD between 1998 and 2013 were analyzed using the Illumina HumanMethylation450K BeadChip. There were 6 patients who developed lymphoma at one or more years after blood sampling, henceforth referred to as \u201cpatients with SjD pre\u2010lymphoma\u201d; 84 patients with SjD did not develop lymphoma, and they are henceforth referred to as \u201cpatients with only SjD.\u201d Epigenome\u2010wide association analyses were adjusted for age, sex, and estimated blood cell\u2013type proportions. Differentially methylated CpG positions (DMPs) were defined by Bonferroni\u2010corrected\n P<\/jats:italic>\n \u2264 1.3 \u00d7 10\n \u22127<\/jats:sup>\n and |\u0394\u03b2| > 0.05. Functional enrichment was assessed using Enrichr and Interferome version 2.01.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 473 autosomal and 1 X\u2010chromosomal DMPs distinguished patients with SjD pre\u2010lymphoma from patients with only SjD, with 87% of DMPs being hypomethylated in patients with SjDpl. The most significant DMP mapped to Thymidine kinase 1 (\n TK1<\/jats:italic>\n ;\n P<\/jats:italic>\n = 7.6 \u00d7 10\n \u221215<\/jats:sup>\n , \u0394\u03b2 = \u22120.16), followed by\n FCER1G<\/jats:italic>\n and\n MDH2<\/jats:italic>\n . Functional annotation revealed enrichment for immune activation, leukocyte signaling, and vesicle\u2010mediated secretion pathways. Patients with SjD pre\u2010lymphoma also exhibited reduced natural killer cells and increased monocyte proportions, consistent with an altered immune milieu.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Distinct DNA methylation changes precede lymphoma in SjD, affecting genes involved in immune regulation, cytotoxic function, and proliferation. Although exploratory and requiring replication, these findings provide a framework for integrating epigenetic, clinical, and serologic markers to inform early risk stratification in patients with SjD.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.70271","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:00:46Z","timestamp":1783584046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Blood\n DNA<\/scp>\n Methylation Changes Precede Lymphoma Diagnosis in Primary Sj\u00f6gren's Disease"],"prefix":"10.1002","author":[{"given":"Hanna","family":"Lidberg","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Rheumatology and Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6078-8826","authenticated-orcid":false,"given":"Cecilia","family":"Fugmann","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Rheumatology and Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7230-8990","authenticated-orcid":false,"given":"Juliana","family":"Imgenberg\u2010Kreuz","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Rheumatology and Science for Life Laboratory Uppsala University Uppsala 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