Of Mice and Women: Toward a Mouse Model of Autoimmune Hepatitis * #

Heneghan, Michael A.; McFarlane, Ian G.

doi:10.1002/hep.20804

Cited by 8 publications

(2 citation statements)

References 36 publications

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“…Autoimmune hepatitis (AIH) remains an enigmatic condition, in-part related to its low incidence (approximately 1.9 cases per 100 000 per year 1 ), and also because of the historical lack of a reliable animal model, which has limited study of pathogenesis. 2 Additionally, AIH represents a condition in which non-organ specific auto-antibodies are detectable in the context of organ specific disease. This dichotomy remains unexplained, and represents a barrier to our fuller understanding of the condition.…”

Section: Introductionmentioning

confidence: 99%

Review article: the modern management of autoimmune hepatitis

Yeoman

Longhi

Heneghan

2010

Aliment Pharmacol Ther

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Aliment Pharmacol Ther 31, 771–787 Summary Background The management of autoimmune hepatitis (AIH) continues to be refined. However, several issues remain unresolved, primarily as a consequence of the low incidence of the disease. This factor has contributed both to a lack of understanding of and a paucity of large scale clinical trials involving therapeutic agents. Aim To summarize the latest evidence regarding the pathogenesis, diagnosis, therapy and long‐term management of AIH with a focus on clinical aspects of the disease. Method We searched PUBMED for articles pertaining to AIH, its pathogenesis, treatment and clinical outcomes, combined with the authors’ own knowledge of the literature. Results Standard therapy (corticosteroids and azathioprine) is effective in more than 80% of patients which renders study of novel agents difficult. Budesonide appears to show equivalence to prednisolone. Available, but limited, data suggest that mycophenolate mofetil, tacrolimus and ciclosporin are all variably effective second line agents. Patients with AIH and cirrhosis are at risk of hepatocellular carcinoma (HCC) and require screening. Patients with end stage liver disease represent excellent candidates for liver transplantation. Conclusions Despite ongoing limitations in the understanding of pathogenesis and difficulties in evaluating novel therapies, the management of AIH continues to evolve slowly. Multi‐centre collaboration is necessary to obtain sufficient patient numbers to undertake good quality therapeutic studies.

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Section: Introductionmentioning

confidence: 99%

Review article: the modern management of autoimmune hepatitis

Yeoman

Longhi

Heneghan

2010

Aliment Pharmacol Ther

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“…model to study this disease [3]. Concanavalin A (ConA) may induce a typical T cell-mediated hepatitis in mice characterized by immune cell infiltration and severe liver damage [4].…”

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confidence: 99%

Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model

et al. 2020

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Background: The prevalence of autoimmune hepatitis (AIH) is increasing, and its early clinical diagnosis is difficult. The pathogenesis of AIH remains unclear, and AIH-related studies are largely limited because of lack of suitable mouse models. Methods: To obtain a good tool for research on AIH, we first established an improved immune-mediated mouse model that can mimic the pathological process of AIH as in the human body, through repeated injections of human cytochrome P450 2D6 (CYP2D6) plasmid. Next, a proteomic analysis based on isobaric tag (IBT) technology was performed to detect the differentially expressed proteins (DEPs), and related biological functions and pathways in the plasma of AIH and normal mice. Finally, we performed enzyme-linked immunosorbent assay (ELISA) to further confirm the most abundant DEP in the plasma of patients with AIH. Results: Autoantibodies and the characteristic pathology of AIH were observed in our mouse model. Inflammatory infiltration also increased in the livers of AIH mice over time and plateaued by day 42 post the first injection. Chronic hepatitis was most severe on day 35 with the development of fibrosis as well, and the plasma of AIH mice were collected for proteomic analysis. A total of 176 DEPs were found in this experiment, of which 148 DEPs were up-regulated and 28 DEPs were down-regulated. Thirty significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (P < 0.05) were detected. Arginine biosynthesis was found to be the most significant pathway involved in the AIH process. During the Gene Ontology (GO) analysis, most DEPs were found to be involved in the binding, cellular, and metabolic processes. Using ELISA, the most overexpressed DEP, serum amyloid A 1 (SAA1), was confirmed to be increased specifically in the plasma of patients with AIH compared to other chronic hepatitis. Different plasma levels of SAA1 were also found related to different grades of inflammation and stages of fibrosis in the liver of patients with AIH. Conclusions: Our study is the first to describe the proteomics analysis of a true sense of AIH mouse model, which is beneficial for a better understanding of AIH pathogenesis and identifying potential biomarkers for its clinical diagnosis.

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Chronic Hepatitis

Lefkowitch

2010

Scheuer's Liver Biopsy Interpretation

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Of Mice and Women: Toward a Mouse Model of Autoimmune Hepatitis * #

Cited by 8 publications

References 36 publications

Review article: the modern management of autoimmune hepatitis

Review article: the modern management of autoimmune hepatitis

Plasma proteomic analysis of autoimmune hepatitis in an improved AIH mouse model

Chronic Hepatitis

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