Towards the pathogenesis of autoimmune liver disease

Mackay, I. R., Davies, Janet M., & Rowley, M. J. (1999) Towards the pathogenesis of autoimmune liver disease. Journal of Autoimmunity, 13(1), pp. 163-169.

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Abstract

There have been recent improvements in the clinical understanding and definition of the major types of autoimmune liver disease. However, still lacking is knowledge of their prevalence and pathogenesis. Three areas of study are in progress in our laboratory. First, in type 1 autoimmune hepatitis, the search continues to identify a liver/disease-specific autoantigenic reactant. Using hepatocyte membrane preparations, immunoblotting has underlined the problem of distinguishing, among multiple reactants, those that may be causally rather than consequentially related to hepatocellular damage. Second, in primary biliary cirrhosis (PBC), the need for population screening to ascertain prevalence and detect preclinical cases can be met by a rapid automated procedure for detection, by specific enzyme inhibition in microtitre wells, of antibody (anti-M2) to the pyruvate dehydrogenase complex E2 subunit (PDC-E2). Third, the structure of the conformational epitope within the inner lipoyl domain of PDC-E2 is being investigated by screening random phage-displayed peptide libraries using PBC sera. This has yielded phage clones in which the sequence of the peptide insert portrays the structure of this epitope, as judged by clustering of PBC-derived sequences to particular branches of a guide-tree that shows relatedness of peptides, and by reactivity of selected phage clones with anti-PDC-E2. Thus phage display identifies a peptide 'mimotope' of the antibody epitope in the inner lipoyl domain of PDC-E2.

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11 citations in Web of Science®

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ID Code: 87928
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: Autoimmune hepatitis, Enzyme-inhibition assay, Mimotope, Phage-displayed libraries, Primary biliary cirrhosis, epitope, peptide library, pyruvate dehydrogenase complex, amino acid sequence, animal tissue, conference paper, enzyme assay, enzyme inhibition, human, human tissue, immunoassay, immunoblotting, liver cell damage, liver membrane, molecular cloning, nonhuman, pathogenesis, phage display, priority journal, rat, Animals, Antigens, Surface, Autoantibodies, Autoantigens, Autoimmune Diseases, Case-Control Studies, Dihydrolipoyllysine-Residue Acetyltransferase, Epitopes, Hepatitis, Autoimmune, Humans, Liver Cirrhosis, Biliary, Liver Diseases, Rats
DOI: 10.1006/jaut.1999.0304
ISSN: 0896-8411
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 01 Oct 2015 00:04
Last Modified: 01 Oct 2015 00:52

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