dc.creator | Zachou K., Arvaniti P., Lyberopoulou A., Sevdali E., Speletas M., Ioannou M., Koukoulis G.K., Renaudineau Y., Dalekos G.N. | en |
dc.date.accessioned | 2023-01-31T11:38:05Z | |
dc.date.available | 2023-01-31T11:38:05Z | |
dc.date.issued | 2022 | |
dc.identifier | 10.1111/liv.15176 | |
dc.identifier.issn | 14783223 | |
dc.identifier.uri | http://hdl.handle.net/11615/80919 | |
dc.description.abstract | Background and Aims: 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. Methods: Ten AIH patients at diagnosis (time-point 1; AIH-tp1), 8/10 following biochemical response (time-point 2; AIH-tp2), 9 primary biliary cholangitis (PBC) and 10 healthy controls (HC) were investigated. Peripheral CD19(+) and CD4(+) cells were isolated. Global DNA methylation (5mC)/hydroxymethylation (5hmC) was studied by ELISAs. mRNA of DNA methylation (DNMT1/3A/3B) and their counteracting hydroxymethylation enzymes (TET1/2/3) was determined by quantitative RT-PCR. Epigenome wide association study (EWAS) was performed in CD4(+) cells (Illumina HumanMethylation 850 K array) in AIH and HC. Total 5mC/5hmC was also assessed by immunohistochemistry (IHC) on paraffin-embedded liver sections. Results: Reduced TET1 and increased DNMT3A mRNA levels characterized CD19(+) and CD4(+)-lymphocytes from AIH-tp1 compared to HC and PBC, respectively, without affecting global DNA 5mC/5hmC. In AIH-tp1, CD4(+) DNMT3A expression was negatively correlated with serum IgG (P =.03). In remission, DNMT3A decreased in both CD19(+) and CD4(+) cells compared to AIH-tp1 (P =.02, P =.03 respectively). EWAS in CD4(+) cells from AIH patients confirmed important modifications in genes implicated in immune responses (HLA-DP, TNF, lnRNAs and CD86). IHC showed increased 5hmC staining of periportal infiltrating lymphocytes in AIH-tp1 compared to HC and PBC. Conclusion: 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. © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | en |
dc.language.iso | en | en |
dc.source | Liver International | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85124765817&doi=10.1111%2fliv.15176&partnerID=40&md5=931d95ce96dfc3e27fd6f59989612323 | |
dc.subject | CD19 antigen | en |
dc.subject | DNA (cytosine 5) methyltransferase 1 | en |
dc.subject | DNA methyltransferase 3A | en |
dc.subject | DNA methyltransferase 3B | en |
dc.subject | enzyme | en |
dc.subject | immunoglobulin G | en |
dc.subject | messenger RNA | en |
dc.subject | tet1 protein | en |
dc.subject | tet2 protein | en |
dc.subject | tet3 protein | en |
dc.subject | unclassified drug | en |
dc.subject | messenger RNA | en |
dc.subject | mixed function oxidase | en |
dc.subject | oncoprotein | en |
dc.subject | TET1 protein, human | en |
dc.subject | adult | en |
dc.subject | Article | en |
dc.subject | autoimmune hepatitis | en |
dc.subject | biochemical analysis | en |
dc.subject | CD4+ T lymphocyte | en |
dc.subject | cell isolation | en |
dc.subject | clinical article | en |
dc.subject | controlled study | en |
dc.subject | DNA methylation | en |
dc.subject | enzyme linked immunosorbent assay | en |
dc.subject | epigenome | en |
dc.subject | female | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | human tissue | en |
dc.subject | illumina sequencing | en |
dc.subject | immunohistochemistry | en |
dc.subject | immunosuppressive treatment | en |
dc.subject | male | en |
dc.subject | paraffin embedding | en |
dc.subject | peripheral lymphocyte | en |
dc.subject | primary biliary cirrhosis | en |
dc.subject | protein expression | en |
dc.subject | real time polymerase chain reaction | en |
dc.subject | remission | en |
dc.subject | autoimmune hepatitis | en |
dc.subject | biliary cirrhosis | en |
dc.subject | complication | en |
dc.subject | DNA methylation | en |
dc.subject | genetics | en |
dc.subject | CD4-Positive T-Lymphocytes | en |
dc.subject | DNA Methylation | en |
dc.subject | Hepatitis, Autoimmune | en |
dc.subject | Humans | en |
dc.subject | Liver Cirrhosis, Biliary | en |
dc.subject | Mixed Function Oxygenases | en |
dc.subject | Proto-Oncogene Proteins | en |
dc.subject | RNA, Messenger | en |
dc.subject | John Wiley and Sons Inc | en |
dc.title | Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis | en |
dc.type | journalArticle | en |