Pathogenesis of autoimmune hepatitis

Liberal, Rodrigo; Longhi, Maria Serena; Mieli‐Vergani, Giorgina; Vergani, Diego

doi:10.1016/j.bpg.2011.09.009

Cited by 138 publications

(105 citation statements)

References 76 publications

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“…This corresponds to the AIH scenario Montano-Loza et al, 2006;Liberal et al, 2015. These alleles are believed to result in faulty antigen processing, with antigenic mimicry resulting in hepatic injury.…”

Section: Discussionmentioning

confidence: 99%

“…Hence the conflictory evidence of inflammation not resulting in fibrosis in pediatric LT versus other inflammatory hepatic diseases. In AIH, the HLA-DRB1*03/04 allele is considered an independent predictor of portal fibrosis (Montano-Loza et al, 2006;de Boer et al, 2014;Liberal et al, 2015). As AIH is the prototype of immune dysregulation-mediated hepatic disease, examining its role in LT recipients is the next logical step: we sought to evaluate "idiopathic" allograft changes by analysing serial PBs in a complication-free LT recipient cohort.…”

Section: Introductionmentioning

confidence: 99%

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Progressive Fibrosis is Driven by Genetic Predisposition, Allo-Immunity, and Inflammation in Pediatric Liver Transplant Recipients

Varma

Ambroise

Komuta

et al. 2016

Journal of Clinical and Experimental Hepatology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Progressive Fibrosis is Driven by Genetic Predisposition, Allo-Immunity, and Inflammation in Pediatric Liver Transplant Recipients

Varma

Ambroise

Komuta

et al. 2016

Journal of Clinical and Experimental Hepatology

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“…1 There is a marked heterogeneity in presentation from asymptomatic elevation of transaminases to acute liver failure to cirrhosis. [2][3][4] 1,4 Type I AIH is more common and seen predominantly in adults while type II AIH is more frequently seen in young children. The diagnosis of AIH is based on the revised or simplified diagnostic criteria, with the revised diagnostic criteria being more suited for patients with atypical features.…”

mentioning

confidence: 99%

Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review

Deswal

Srivastava

2017

Journal of Clinical and Experimental Hepatology

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Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. The metabolism of AZA is complex and mediated by multiple enzymes. After absorption and getting converted to 6MP, it is converted to 6-thiouric acid, 6-methyl mercaptopurine (6MMP) and 6-thioguanine (6TG) by different enzymes. Elevated 6MMP levels are associated with hepatotoxicity and also poor efficacy due to simultaneous lower levels of 6TG, which is the active drug metabolite related to both efficacy and myelosuppression. Allopurinol, a xanthine oxidase inhibitor shifts the metabolism of AZA away from 6MMP toward 6TG. This combination of allopurinol with reduced dose of AZA is an alternative to more expensive and toxic second line therapy to induce remission in patients with AIH. This article discusses the mechanism of action of allopurinol in inducing response to AZA, reviews the published literature on this combination therapy and gives guidelines on the use of allopurinol in patients with AIH. ( J CLIN EXP HEPATOL 2017;7:55-62)

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“…It also occurs as an accidental encounter of structural resemblances, particularly in the immune system, sometimes culminating in pathological conditions such as autoimmune disorders (5)(6)(7)(8). The molecular mimicry between self and viral or bacterial peptides generally leads to the activation of self-reactive T cells resulting in autoimmune pathologies, for example, multiple sclerosis, autoimmune hepatitis, and myocarditis (9)(10)(11). The humoral immune system has also been shown to produce autoreactive Abs, some of which are also associated with cancers (12,13).…”

mentioning

confidence: 99%

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

Tapryal

Gaur

Kaur

et al. 2013

The Journal of Immunology

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Molecular mimicry manifests antagonistically with respect to the specificity of immune recognition. However, it often occurs because different Ags share surface topologies in terms of shape or chemical nature. It also occurs when a flexible paratope accommodates dissimilar Ags by adjusting structural features according to the antigenic epitopes or differential positioning in the Ag combining site. Toward deciphering the structural basis of molecular mimicry, mAb 2D10 was isolated from a maturing immune response elicited against methyl α-d-mannopyranoside and also bound equivalently to a dodecapeptide. The physicochemical evidence of this carbohydrate–peptide mimicry in the case of mAb 2D10 had been established earlier. These studies had strongly suggested direct involvement of a flexible paratope in the observed mimicry. Surprisingly, comparison of the Ag-free structure of single-chain variable fragment 2D10 with those bound to sugar and peptide Ags revealed a conformationally invariant state of the Ab while binding to chemically and structurally disparate Ags. This equivalent binding of the two dissimilar Ags was through mutually independent interactions, demonstrating functional equivalence in the absence of structural correlation. Thus, existence of a multispecific, mature Ab in the secondary immune response was evident, as was the plasticity in the interactions while accommodating topologically diverse Ags. Although our data highlight the structural basis of receptor multispecificity, they also illustrate mechanisms adopted by the immune system to neutralize the escape mutants generated during pathogenic insult.

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Pathogenesis of autoimmune hepatitis

Cited by 138 publications

References 76 publications

Progressive Fibrosis is Driven by Genetic Predisposition, Allo-Immunity, and Inflammation in Pediatric Liver Transplant Recipients

Progressive Fibrosis is Driven by Genetic Predisposition, Allo-Immunity, and Inflammation in Pediatric Liver Transplant Recipients

Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

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