Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis

Zachou, Kalliopi; Arvaniti, Pinelopi; Lyberopoulou, Aggeliki; Sevdali, Eirini; Speletas, Matthaios; Ιωάννου, Μαρία; Koukoulis, George Κ.; Renaudineau, Yves; Dalekos, George Ν.

doi:10.1101/2021.07.01.21259836

Cited by 4 publications

(4 citation statements)

References 47 publications

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“…83 In addition, epigenetic factors that alter gene expression without changing the nucleotide sequence may also contribute to the clinical expression and phenotype of the disease. 84 Multiple hypo-methylated genes have been described in the CD4 positive and CD19 positive T lymphocytes of patients with autoimmune hepatitis, 85 and the circulating micro-ribonucleic acids miR-21 and miR-122 correlate with laboratory and histological features of liver inflammation. 86 Moreover, outside the major histocompatibility complex, single nucleotide polymorphisms concerning pro-inflammatory as well as regulatory pathways have also been described in autoimmune hepatitis, affecting genes such as those for tumor necrosis factor, CTLA-4/CD28, FAS, TGFγ1, and interleukin-4.…”

Section: Genetics and Epigeneticsmentioning

confidence: 99%

Diagnosis and management of autoimmune hepatitis

Muratori

Lohse

Lenzi

2023

BMJ

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Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed. The clinical presentation is often that of acute hepatitis, sometimes very severe; less frequently, it can be insidious or completely asymptomatic. The disease can affect people of any age and is more common in women; its incidence and prevalence seem to be on the rise worldwide. An abnormal immune response targeting liver autoantigens and inducing persistent and self-perpetuating liver inflammation is the pathogenic mechanism of the disease. A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis. Prompt response to treatment with corticosteroids and other immunomodulatory drugs is almost universal and supports the diagnosis. The aims of treatment are to induce and maintain long term remission of liver inflammation. Treatment can often even reverse liver fibrosis, thus preventing progression to advanced cirrhosis and its complications. Most patients need lifelong maintenance therapy, and repeated follow-up in experienced hands improves the quality of care and quality of life for affected patients.

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Section: Genetics and Epigeneticsmentioning

confidence: 99%

Diagnosis and management of autoimmune hepatitis

Muratori

Lohse

Lenzi

2023

BMJ

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“…A previous clinical study reported a correlation between the DNA methylation status in certain immune cells such as CD4 + and CD19 + lymphocytes and disease activity. Altered expression of enzymes involved in DNA methylation, TET1 and DNMT3A, characterizes lymphocytes in AIH ( 38 ). Further studies are required in order to confirm this association.…”

Section: Epigenetics In Various Liver Diseasesmentioning

confidence: 99%

Epigenetics in inflammatory liver diseases: A clinical perspective (Review)

Isac

Rababoc

et al. 2022

Exp Ther Med

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Inflammatory liver diseases are, nowadays, multifactorial and wide-spread, thus having an important socio-economic impact. Although the therapeutic algorithms are well-known in hepatitis, regardless of etiology, strategies to identify inflammatory hepatic lesions in early stages and to develop new epigenetic therapies should be prioritized. The main entities of inflammatory liver disease are: alcoholic and non-alcoholic fatty liver disease, autoimmune hepatitis, viral hepatitis and Wilson disease. The main epigenetic processes include: DNA methylation/demethylation, which imply changes in DNA tertiary structure; post-translational histone covalent changes (methylation/demethylation, acetylation/deacetylation, ubiquitination), that cause DNA-histone instability; synthesis of small, non-coding RNA molecules, called microRNAs, that modulate translational potential of transcripts (mRNAs) and post-translational modification of polypeptide chains. Consequently, the epigenetic interactions aforementioned, play an important modulatory role in disease progression and response to conventional therapies The present review focused on the main epigenetic changes in inflammatory liver conditions, considering a new perspective: Epigenetic therapy. This approach is more than welcomed, taking into consideration that conventional therapeutic strategies are almost exhausted.

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“…Even though the etiology of AIH is still not clear, there is evidence that the development of the disease is based on genetic predisposition, environmental and epigenetic factors [8,[10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Finally, DNA methylation, histone adjustments, and micro-RNAs (miRNAs) are examples of epigenetic alterations that may regulate gene expression even though they do not change the DNA sequence [10]. We recently found DNA methylation changes in circulating immune cells and at the histological level of AIH patients, which were associated with disease activity and influenced by immunosuppressive treatment [12]. This review aims to summarize the recent challenges and advances in AIH diagnosis and management.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in the diagnosis and management of autoimmune hepatitis

Dalekos¹,

Samakidou²,

Lyberopoulou³

et al. 2022

Polish Archives of Internal Medicine

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Autoimmune hepatitis (AIH) is an acute or chronic inflammatory disease of the liver caused by an unclear immune response that affects people from all ethnic groups irrespective of age or sex. It is characterized by hyperglobulinemia, circulating autoantibodies and liver inflammation. The clinical picture of the disease varies from asymptomatic and/or mild to severe acute hepatitis or liver failure. A timely and prompt diagnosis is of utmost importance to prevent progression to advanced liver disease by immediate initiation of immunosuppressive treatment. So far, several diagnosing scoring systems have incorporated the demographics, biochemical, clinical, and histological characteristics of the disease.However, due to the high heterogeneity of the disease presentation, AIH diagnosis remains challenging. Most patients initially respond to first-line treatment, which consists of corticosteroids combined with azathioprine while some authorities also suggest the use of mycophenolate mofetil instead. However, insufficient response and intolerance due to side effects are common, so a significant proportion of patients requires second-and/or third-line therapies. Herein, we review the challenges and recent advances in AIH diagnosis and management.

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Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis

Cited by 4 publications

References 47 publications

Diagnosis and management of autoimmune hepatitis

Diagnosis and management of autoimmune hepatitis

Epigenetics in inflammatory liver diseases: A clinical perspective (Review)

Recent advances in the diagnosis and management of autoimmune hepatitis

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