Molecular basis of mitochondrial autoreactivity in primary biliary cirrhosis.

Immunology Today
I R Mackay, M E Gershwin

Abstract

Primary biliary cirrhosis (PBC), styled as a model autoimmune disease, has a very close association with antibodies to mitochondrial antigens. The cloning of cDNAs for mitochondrial antigens led to their identification as the three enzymes of the 2-oxo-acid dehydrogenase family which includes pyruvate dehydrogenase (PDH). The autoantigen is associated with the E2 subunit of these enzymes. PDH is the 70-74 kDa antigen previously identified by immunoblotting. An immunodominant site (autoepitope) can be mapped to a sequence of PDH-E2 which is the site of attachment of the functionally important lipoic acid prosthetic group. Here, Ian Mackay and Eric Gershwin discuss how autoantigen identification and epitope mapping has now proceeded further in PBC than in other autoimmune diseases, and will allow access to critically important questions on pathogenesis of PBC in particular and autoimmunity in general.

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