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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Primary biliary cirrhosis: paradigm or paradox for autoimmunity.

Primary biliary cirrhosis has been classified as a model autoimmune disease based on striking defects in immune regulation and the presence of autoantibodies to mitochondria. Until recently the significance and definition of mitochondrial autoreactivity was unknown. Since 1987, there has been a vast improvement in the understanding and definition of the biochemical and molecular target autoantigens. The cloning of complementary DNAs for mitochondrial antigens has led to the identification of three enzymes of the 2-oxo-acid dehydrogenase family as the targets of the autoantibodies to mitochondria in patients with primary biliary cirrhosis. The major reactive autoantigen is the E2 subunit of pyruvate dehydrogenase. Immunodominant sites on pyruvate dehydrogenase E2 (autoepitopes) have been mapped and have been shown to be the site of attachment of the functionally important lipoic acid prosthetic group. The autoepitope for the other enzymes probably occupies an equivalent site on the enzyme. The availability and definition of these mitochondrial autoepitopes have allowed specific questions to be addressed relating to the processing and targeting of these autoantigens as well as further studies on mechanisms of immunopathology. Similarly, the availability of well-defined autoantigens could contribute to the development of valid animal models in addition to the already described reproduction of the biliary ductular lesions by transfer of peripheral blood lymphocytes from patients with primary biliary cirrhosis into severe combined immunodeficient mice. Such models will facilitate specific study of the role of major histocompatibility complex expression and the characterization of T-cell reactivity. Thus, primary biliary cirrhosis is a key example of significant progress in autoimmunity being made by use of recombinant DNA technology.[1]


  1. Primary biliary cirrhosis: paradigm or paradox for autoimmunity. Gershwin, M.E., Mackay, I.R. Gastroenterology (1991) [Pubmed]
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