{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:09:33Z","timestamp":1790104173877,"version":"4.0.1"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010116","name":"Medicinska Underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010116","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p>\n                    The HLA region, especially HLA class I and II genes, which encode molecules for antigen presentation to T cells, plays a major role in the predisposition to autoimmune disorders. To clarify the mechanisms behind this association, we examined genome\u2010wide DNA methylation by microarrays to cover over 850,000 CpG sites in the CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells of healthy subjects homozygous either for\n                    <jats:italic>DRB1*15\u2010DQA1*01\u2010DQB1*06:02<\/jats:italic>\n                    (DR2\u2010DQ6,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914), associated with a strongly decreased T1D risk,\n                    <jats:italic>DRB1*03\u2010DQA1*05\u2010DQB1*02<\/jats:italic>\n                    (DR3\u2010DQ2,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919), or\n                    <jats:italic>DRB1*04:01\u2010DQA1*03\u2010DQB1*03:02<\/jats:italic>\n                    (DR4\u2010DQ8,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917), associated with a moderately increased T1D risk. In total, we discovered 14 differentially methylated CpG probes, of which 10 were located in the HLA region and six in the\n                    <jats:italic>HLA\u2010DRB1<\/jats:italic>\n                    locus. The main differences were between the protective genotype DR2\u2010DQ6 and the risk genotypes DR3\u2010DQ2 and DR4\u2010DQ8, where the DR2\u2010DQ6 group was hypomethylated compared to the other groups in all but four of the differentially methylated probes. The differences between the risk genotypes DR3\u2010DQ2 and DR4\u2010DQ8 were small. Our results indicate that HLA variants have few systemic effects on methylation and that their effect on autoimmunity is conveyed directly by HLA molecules, possibly by differences in expression levels or function.\n                  <\/jats:p>","DOI":"10.1111\/tan.15548","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T04:30:43Z","timestamp":1718685043000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The effect of type 1 diabetes protection and susceptibility associated\n                    <scp>HLA<\/scp>\n                    class\n                    <scp>II<\/scp>\n                    genotypes on\n                    <scp>DNA<\/scp>\n                    methylation in immune cells"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-060X","authenticated-orcid":false,"given":"Sirpa","family":"Pahkuri","sequence":"first","affiliation":[{"name":"Immunogenetics Laboratory, Institute of Biomedicine University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Stem Cells and Metabolism Research Program University of Helsinki  Helsinki Finland"},{"name":"Department of Biosciences and Nutrition Karolinska Institutet  Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milla","family":"Valta","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Institute of Biomedicine University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Nyg\u00e5rd","sequence":"additional","affiliation":[{"name":"Immunogenetics Laboratory, Institute of Biomedicine University of Turku  Turku Finland"},{"name":"Department of Clinical Microbiology, Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Knip","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Research Program for Clinical and Molecular Metabolism University of Helsinki  Helsinki Finland"},{"name":"Tampere Center for Child Health Research Tampere University Hospital  Tampere Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Kere","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Stem Cells and Metabolism Research Program University of Helsinki  Helsinki 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