Primary biliary cirrhosis and autoimmune hepatitis

Apotopes and epitopes

Ana Lleo, Shinji Shimoda, Hiromi Ishibashi, M. Eric Gershwin

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalJournal of Gastroenterology
Volume46
Issue numberSUPPL. 1
DOIs
StatePublished - Jan 2011

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Autoimmune Hepatitis
Biliary Liver Cirrhosis
Epitopes
Insemination, Artificial, Homologous
Autoimmune Diseases
Liver Diseases
Dihydrolipoyllysine-Residue Acetyltransferase
Intrahepatic Bile Ducts
Cytochrome P-450 CYP2D6
Organ Specificity
Antibody Specificity
Histocompatibility Antigens Class II
Autoantigens
Hepatocytes
Mitochondria
Chronic Disease
Epithelial Cells
Apoptosis
T-Lymphocytes

Keywords

  • Apotope
  • Autoimmunity
  • Biliary epithelial cell
  • Hepatocyte

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Primary biliary cirrhosis and autoimmune hepatitis : Apotopes and epitopes. / Lleo, Ana; Shimoda, Shinji; Ishibashi, Hiromi; Gershwin, M. Eric.

In: Journal of Gastroenterology, Vol. 46, No. SUPPL. 1, 01.2011, p. 29-38.

Research output: Contribution to journalArticle

Lleo, Ana ; Shimoda, Shinji ; Ishibashi, Hiromi ; Gershwin, M. Eric. / Primary biliary cirrhosis and autoimmune hepatitis : Apotopes and epitopes. In: Journal of Gastroenterology. 2011 ; Vol. 46, No. SUPPL. 1. pp. 29-38.
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