Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis

S. M. Krams, C. D. Surh, R. L. Coppel, A. Ansari, B. Ruebner, M. Eric Gershwin

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Abstract

The availability of recombinant mitochondiral 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.

Original languageEnglish (US)
Pages (from-to)411-416
Number of pages6
JournalHepatology
Volume9
Issue number3
StatePublished - 1989

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Dihydrolipoyllysine-Residue Acetyltransferase
Biliary Liver Cirrhosis
Immunization
Peptides
Antibodies
Autoantigens
Guinea Pigs
Rabbits
Inbred CBA Mouse
Mitochondrial Proteins
Enzymes
Macaca mulatta
Pyruvic Acid
Recombinant Proteins
Antibody Formation
Liver Diseases
Epitopes
Oxidoreductases
Serum

ASJC Scopus subject areas

  • Hepatology

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Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis. / Krams, S. M.; Surh, C. D.; Coppel, R. L.; Ansari, A.; Ruebner, B.; Gershwin, M. Eric.

In: Hepatology, Vol. 9, No. 3, 1989, p. 411-416.

Research output: Contribution to journalArticle

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