Primary biliary cirrhosis: Inhibition Of pyruvate dehydrogenase complex activity by autoantibodies specific for E1 α, a non-lipoic acid containing mitochondrial enzyme

David R. Fregeau, Thomas E. Roche, Paul A. Davis, Ross Coppel, M. Eric Gershwin

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Antimitochondrial antibodies (AMA) are serologically characteristic of patients with PBC. Four Ag recognized by AMA have been recently identified, including protein X and the acyltransferases of three related multienzyme complexes: the pyruvate dehydrogenase complex (PDC), the branched-chain α-ketoacid dehydrogenase complex, and the α-ketoglutarate dehydrogenase complex. Each of these enzymes contains one or more lipoyl moieties as part of a major functional site. In addition, epitope mapping has suggested that the AMA target is this lipoic acid-binding region. In this report we demonstrate that sera from patients with PBC also recognize the E1 component (pyruvate dehydrogenase, EC of PDC. PDC-E1 is composed of α and β-chains. Reactivity with the 41 kDα chain was detected in 80 of 120 (66%) PBC sera by immunoblotting against purified PDC-E1; 2 of 120 sera also demonstrated reactivity with the 34 kDβ chain. In contrast, sera from patients with SLE, chronic active hepatitis, or progressive sclerosing cholangitis as well as sera from healthy volunteers did not react with PDC-E1. Furthermore, affinity-purified PBC sera against PDC-E1α were able to inhibit PDC enzyme activity, whereas control sera could not. PDC-E1α is now the fifth mitochondrial autoantigen of PBC to be identified. Similar to the four previously identified autoantigens, AMA appear to be directed to a functional site of PDC-E1α inasmuch as they are able to inhibit enzyme function. However, PDC-E1α is also unique in that it is the first identified mitochondrial autoantigen which does not contain lipoic acid.

Original languageEnglish
Pages (from-to)1671-1676
Number of pages6
JournalJournal of Immunology
Issue number5
Publication statusPublished - 1 Mar 1990
Externally publishedYes

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