{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:06:18Z","timestamp":1794366378767,"version":"4.9.0"},"reference-count":68,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Long interspersed nuclear elements 1 (LINE\u20101) are the most abundant and the only autonomous mobile elements in the human genome. When their epigenetic repression is removed, it can lead to disease, such as autoimmune diseases and cancer. Coeliac disease (CeD) is an immune\u2010mediated disease triggered by an abnormal T\u2010cell response to dietary gluten and a predisposing condition of small bowel adenocarcinoma (SBA), frequently characterized by epigenetic alterations. The aim of this work was to assess LINE\u20101 methylation by bisulphite pyrosequencing and NanoString\u00ae gene transcription analysis in 38 CeD\u2010SBAs compared with 25 SBAs associated with Crohn's disease (CrD\u2010SBAs) and 25 sporadic SBAs (S\u2010SBA). Both analyses were also performed in duodenal mucosae from 12 untreated CeD patients (UCD) and 19 treated CeD patients (TCD), and in 11 samples of normal intestinal mucosa to better investigate the role of LINE\u20101 deregulation in CeD and in CeD\u2010SBA. A significant loss of LINE\u20101 methylation was observed in CeD\u2010SBAs and in mucosae from UCD patients (with very similar methylation levels) compared with controls. By contrast, a restoration of normal LINE\u20101 methylation levels was found in TCD mucosae after a strict gluten\u2010free diet. LINE\u20101 hypomethylation does not lead to expression of ORF1 and ORF2, with the only exception being for one CeD\u2010SBA. The expression analysis of enzymes modulating DNA methylation and inflammatory genes confirmed that CeD\u2010SBA shared a very similar expression profile of UCD mucosae showing a strong upregulation of genes involved in inflammation, immune response, and T\u2010cell activity compared with TCD mucosae. For the first time, this work demonstrates that loss of DNA methylation is an intrinsic epigenetic feature of CeD, accompanying the immune response as a reversible mechanism in patients following a strict gluten\u2010free diet, and suggests the possible role of LINE\u20101 hypomethylation in promoting cell adaptability during the gliadin\u2010related inflammatory process. \u00a9 2024 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6371","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T06:11:16Z","timestamp":1732687876000},"page":"99-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>LINE<\/scp>\n                    \u20101 hypomethylation characterizes the inflammatory response in coeliac disease associated\u2010intestinal mucosa and small bowel adenocarcinomas"],"prefix":"10.1002","volume":"265","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2130-6669","authenticated-orcid":false,"given":"Laura","family":"Libera","sequence":"first","affiliation":[{"name":"Unit of Pathology, Department of Medicine and Technological Innovation University of Insubria  Varese Italy"},{"name":"Hereditary Cancer Research Centre, Department of Medicine and Technological Innovation University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Vanoli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Unit of Anatomic Pathology University of Pavia  Pavia Italy"},{"name":"Unit of Anatomic Pathology Fondazione IRCCS San Matteo Hospital  Pavia 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