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Primary biliary cirrhosis and autoimmune hepatitis: apotopes and epitopes

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Abstract

Autoimmune liver diseases (ALDs) represent a wide spectrum of chronic inflammatory diseases that are characterized by an immune-mediated attack against either hepatocytes (in the case of autoimmune hepatitis types 1 and 2, AIH-1, 2) or cholangiocytes (in primary biliary cirrhosis, PBC). PBC is considered a model autoimmune disease due to the homogeneity of patients, the high specificity of antimitochondrial antibodies (AMAs), and the specificity of biliary epithelial cell (BEC) destruction. It ensues from a multi-lineage loss of tolerance to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). One of the major unanswered questions in the pathogenesis of PBC is the specificity of small intrahepatic bile duct attack while PDC-E2 is present in mitochondria of nucleated cells. Recent findings suggest that the apoptosis of BECs may be of considerable importance for understanding PBC, and that they are more than simply an innocent victim of an immune attack. Rather, they attract immune attack by virtue of the unique biochemical mechanisms by which they handle PDC-E2. The role of apoptotic cells in AIH is not well defined, but advances in the study of autoreactive T cells stem mostly from AIH type 2, where the main autoantigen (CYP2D6) is known, enabling the characterization of antigen-specific immune responses. This review article is intended to provide a critical overview of current evidence on tissue specificity in ALDs, as well as the characteristics of the relevant epitopes and apotopes and their biological and clinical significance.

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Authors and Affiliations

  1. Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA, USA

    Ana Lleo & M. Eric Gershwin

  2. Hepatobiliary Immunopathology Unit, IRCCS-Istituto Clinico Humanitas, Rozzano, Italy

    Ana Lleo

  3. Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Shinji Shimoda

  4. Clinical Research Center, Nagasaki Medical Center, Nagasaki, Japan

    Hiromi Ishibashi

  5. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA

    M. Eric Gershwin

Authors
  1. Ana Lleo
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  2. Shinji Shimoda
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  3. Hiromi Ishibashi
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  4. M. Eric Gershwin
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Correspondence to M. Eric Gershwin.

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Lleo, A., Shimoda, S., Ishibashi, H. et al. Primary biliary cirrhosis and autoimmune hepatitis: apotopes and epitopes. J Gastroenterol 46 (Suppl 1), 29–38 (2011). https://doi.org/10.1007/s00535-010-0303-8

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  • DOI: https://doi.org/10.1007/s00535-010-0303-8

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