title: [The association between autoantibodies to enzyme and diseases--with special reference to antibodies to pyruvate dehydrogenase complex (PDH)].
abstract: A serological feature of primary biliary cirrhosis (PBC) is the presence of high-titer antimitochondrial autoantibodies (AMA) in patient sera. Five different target mitochondrial autoantigens recognized by sera from PBC patients have been identified as subunits of the 2-oxoacid dehydrogenase complex (2-OADC), of which pyruvate dehydrogenase complex-E2 (PDH-E2) is the most prominent antigenic component. Extensive molecular and immunological studies in PBC such as cloning of mitochondrial autoantigens, mapping of both T and B cell epitopes and immunohistochemical studies have provided valuable reagents in the understanding of immunopathogenesis of PBC. We mapped the epitope recognized by AMA specific to 2-oxoglutarate dehydrogenase complex-E2 (OGDC-E2) in patients with PBC using full-length rat OGDC-E2 cDNA and a series of expression clones spanning the entire molecule. It appears that the epitope is dependent on conformation and includes the lipoic acid-binding region. Furthermore we have taken advantage of the antigenic mapping studies of PDC-E2, OGDC-E2 and branched chain 2-oxoacid dehydrogenase complex-E2 (BCOADC-E2) subunits and designed a hybrid clone, pML-MIT3, that expressed three different immunodominant epitopes. Our results indicate that an immunoassay using recombinant, cloned autoantigen is a powerful and very specific method for detecting AMA in PBC.
authors.affiliation: Department of Clinical Pathology, Nihon University School of Medicine, Tokyo.
authors.forename: S
authors.initials: S
authors.lastname: Moteki
authors.forename: S
authors.initials: S
authors.lastname: Amaki
authors.forename: E
authors.initials: E
authors.lastname: Nakano
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D000939:Epitopes; D006801:Humans; D015151:Immunoblotting; D007658:Ketone Oxidoreductases / Q000276:immunology*; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis*; D008928:Mitochondria / Q000201:enzymology / Q000276:immunology; D009097:Multienzyme Complexes / Q000276:immunology*; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology*; D051381:Rats; D011994:Recombinant Proteins
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D000939:Epitopes; D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; D011994:Recombinant Proteins; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)