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Review
. 2021 Sep 21:4:100125.
doi: 10.1016/j.jtauto.2021.100125. eCollection 2021.

Impact of genetic and environmental factors on autoimmune hepatitis

Kalliopi Zachou  1 , Pinelopi Arvaniti  1 , Aggeliki Lyberopoulou  1 , George N Dalekos  1
Affiliations
Review

Impact of genetic and environmental factors on autoimmune hepatitis

Kalliopi Zachou et al. J Transl Autoimmun. .

Abstract

Autoimmune hepatitis (AIH) is a chronic non-resolving liver disease characterized by diffuse hypergammaglobulinemia, the presence of autoantibodies and characteristic histological findings. The disease can have catastrophic outcome with the development of end-stage liver disease if misdiagnosed/undiagnosed and left untreated. AIH pathogenesis remains obscure and the main hypothesis supports its development in genetically predisposed individuals after being exposed to certain environmental triggers. Genetic predisposition is linked to the presence of certain HLA alleles, mainly HLA-DR3 and HLA-DR4. However, a wide number of non-HLA epitopes have also been associated with the disease although data vary significantly among different ethnic groups. Therefore, it is likely that epigenetic alterations may also play a crucial role in disease's pathogenesis, although not yet extensively studied. The aim of this review was to summarize the genetic and environmental factors that have been associated with AIH, but also to open new insights towards the role of epigenetic modifications in the etiology of the disease.

Keywords: Autoimmune hepatitis; Epigenetics; HLA-DR; Single nucleotide polymorphisms.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
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.
See this image and copyright information in PMC

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