Semin Liver Dis 2005; 25(3): 337-346
DOI: 10.1055/s-2005-916325
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Immune Response to Mitochondrial Autoantigens

Hiromi Ishibashi1 , Shinji Shimoda2 , M. Eric Gershwin3
  • 1Director General, Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center; Professor, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki Japan
  • 2Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • 3Distinguished Professor of Medicine, The Jack and Donald Chia Professor of Medicine, Chief, Division of Rheumatology, Allergy and Clinical Immunology, Genome and Biomedical Sciences Facility, University of California at Davis, Davis, California
Further Information

Publication History

Publication Date:
06 September 2005 (online)

ABSTRACT

Similar to other autoimmune diseases, there are intense humoral and cellular responses to intracytoplasmic antigens in primary biliary cirrhosis (PBC). The autoantigens against antimitochondrial antibodies (AMAs) in PBC are located on the inner mitochondrial membrane and are identified as members of the 2-oxo-acid dehydrogenase complexes (2-OADCs), of which the E2 subunit of pyruvate dehydrogenase complex (PDC-E2) is the major autoantigen; AMAs are is present in approximately 90 to 95% of PBC sera. An orchestrated immune response against the intrahepatic biliary epithelial cell (BEC) through 2-OADC-specific CD4+ helper T cells and CD8+ CTL are thought to be the major players in the immunological destruction of BECs in PBC. We believe that a prior/primary event of specific intrahepatic BEC malfunction (possibly caused by environmental insults such as xenobiotics and microorganisms) is responsible for the breaking of self-tolerance to 2-OADC and leads to BEC destruction. The generation of 2-OADC-specific T cells further accelerates the damage of BEC. In addition, immunoglobulin A AMAs may participate in the destruction of BECs by damaging mitochondria.

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Hiromi IshibashiM.D. 

Clinical Research Center, National Hospital Organization Nagasaki Medical Center

Omura, Nagasaki 856-8562, Japan

Email: hiishibashi-gi@umin.ac.jp