{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:52:40Z","timestamp":1772160760948,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Little is known about the impact of DNA methylation modifications on autoimmune hepatitis (AIH) pathogenesis and therapeutic response. We investigated the potential alterations of DNA methylation in AIH peripheral lymphocytes at diagnosis and remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ten AIH patients at diagnosis (time\u2010point 1; AIH\u2010tp1), 8\/10 following biochemical response (time\u2010point 2; AIH\u2010tp2), 9 primary biliary cholangitis (PBC) and 10 healthy controls (HC) were investigated. Peripheral CD19(+) and CD4(+) cells were isolated. Global DNA methylation (5\n                      <jats:sup>m<\/jats:sup>\n                      C)\/hydroxymethylation (5\n                      <jats:sup>hm<\/jats:sup>\n                      C) was studied by ELISAs. mRNA of DNA methylation (DNMT1\/3A\/3B) and their counteracting hydroxymethylation enzymes (TET1\/2\/3) was determined by quantitative RT\u2010PCR. Epigenome wide association study (EWAS) was performed in CD4(+) cells (Illumina HumanMethylation 850\u00a0K array) in AIH and HC. Total 5\n                      <jats:sup>m<\/jats:sup>\n                      C\/5\n                      <jats:sup>hm<\/jats:sup>\n                      C was also assessed by immunohistochemistry (IHC) on paraffin\u2010embedded liver sections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Reduced TET1 and increased DNMT3A mRNA levels characterized CD19(+) and CD4(+)\u2010lymphocytes from AIH\u2010tp1 compared to HC and PBC, respectively, without affecting global DNA 5\n                      <jats:sup>m<\/jats:sup>\n                      C\/5\n                      <jats:sup>hm<\/jats:sup>\n                      C. In AIH\u2010tp1, CD4(+) DNMT3A expression was negatively correlated with serum IgG (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.03). In remission, DNMT3A decreased in both CD19(+) and CD4(+) cells compared to AIH\u2010tp1 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.02,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.03 respectively). EWAS in CD4(+) cells from AIH patients confirmed important modifications in genes implicated in immune responses (HLA\u2010DP, TNF, lnRNAs and CD86). IHC showed increased 5\n                      <jats:sup>hm<\/jats:sup>\n                      C staining of periportal infiltrating lymphocytes in AIH\u2010tp1 compared to HC and PBC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Altered TET1 and DNMT3A expressions, characterize peripheral lymphocytes in AIH. DNMT3A was associated with disease activity and decreased following remission. Gene DNA methylation modifications affect immunological pathways that may play an important role in AIH pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15176","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T12:08:26Z","timestamp":1643803706000},"page":"1355-1368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Altered\n                    <scp>DNA<\/scp>\n                    methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis"],"prefix":"10.1111","volume":"42","author":[{"given":"Kalliopi","family":"Zachou","sequence":"first","affiliation":[{"name":"Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) General University Hospital of Larissa  Larissa Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinelopi","family":"Arvaniti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) General University Hospital of Larissa  Larissa Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aggeliki","family":"Lyberopoulou","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) General University Hospital of Larissa  Larissa Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini","family":"Sevdali","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department 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Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Renaudineau","sequence":"additional","affiliation":[{"name":"INSERN U1291, CNR U5051, University Toulouse III Toulouse Institute for infectious and inflammatory diseases  Toulouse France"},{"name":"Department of Immunology Purpan University Hospital Toulouse  Toulouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-8464","authenticated-orcid":false,"given":"George N.","family":"Dalekos","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) General University Hospital of Larissa  Larissa 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