DNA methylation alterations in peripheral immune cells and liver sections from AIH patients. Increased DNMT3A and reduced TET1 expression is observed in CD4(+) and CD19(+) lymphocytes from AIH patients at diagnosis compared to PBC patients and healthy controls, respectively. DNMT3A expression is negatively associated with circulating IgG levels, while Immunosuppressive treatment reduces DNMT3A levels in AIH at remission. Alterations in DNMT3A and TET1 transcriptional levels are associated with altered methylation status of several genes implicated in immune response pathways. Immunohistochemistry on liver sections from AIH patients at diagnosis reveals a dense 5hmC staining of periportal infiltrating lymphocytes indicating hypomethylation.
Abbreviations: AIH: autoimmune hepatitis, EWAS: epigenome wide association studies, DNMT3A: DNA methyl-transferase 3A, TET1: ten-eleven-translocation enzyme 1, IHC: immunohistochemistry, IgG: immunoglobulin G, HLADP: human leucocyte antigen DP, lnRNA: long non-coding RNA, TNF: tumor necrosis factor, 5 hmC: 5-hydroxymethyl cytosine.