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Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis
Author(s) -
Krams Sheri M.,
Surh Charles D.,
Coppel Ross L.,
Ansari Aftab,
Ruebner Boris,
Gershwin M. Eric
Publication year - 1989
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840090311
Subject(s) - primary biliary cirrhosis , biology , pyruvate dehydrogenase complex , antibody , dihydrolipoamide dehydrogenase , epitope , recombinant dna , biochemistry , immunology , enzyme , gene
The availability of recombinant mitochondrial autoantigens may permit the experimental study of the pathophysiology of primary biliary cirrhosis. Previously, we demonstrated that high‐titer antibodies to the 74 kD mitochondrial autoantigen dihydrolipoamide acetyltransferase could be generated when BALB/c mice were immunized with purified recombinant protein. Based on these data, we attempted an 8‐month study to induce antibodies and liver dysfunction by immunizing AKR/J, C3H/J and CBA/HeJ mice as well as rats, guinea pigs, rabbits and rhesus monkeys with purified recombinant human dihydrolipoamide acetyltransferase. Antibodies to dihydrolipoamide acetyltransferase were readily induced and detected in all species of experimental animals with species and strain differences in the titer of the responses. Of particular interest, rabbits and guinea pigs produced antibodies which were specifically reactive with the functional site of dihydrolipoamide acetyltransferase, whereas the other strains and species produced antibodies to other epitopes on the molecule. Finally, similar to data on humans with primary biliary cirrhosis, the pyruvate dehydrogenase enzyme pathway was inhibited in the presence of immunized animal sera. These data imply that features other than simply an antibody response to mitochondrial enzymes are required for the development of primary biliary cirrhosis. Further studies will be necessary to determine the mechanisms by which mitochondrial proteins elicit an immune response.