title: Enzyme inhibitory autoantibodies to pyruvate dehydrogenase complex in primary biliary cirrhosis differ for mammalian, yeast and bacterial enzymes: implications for molecular mimicry.
abstract: Primary biliary cirrhosis is a chronic autoimmune disease in which serum autoantibodies against the mitochondrial 2-oxo acid dehydrogenase enzyme complexes (M2 antibodies) are regularly present. Molecular mimicry of host proteins by bacterial counterparts is a suggested explanation for the origin of these autoantibodies. We tested this hypothesis by measuring the functional reactivity of serum autoantibodies by means of an enzyme inhibition assay against pyruvate dehydrogenase complex from different sources: mammalian, Saccharomyces cerevisiae and Escherichia coli. The 10 primary biliary cirrhosis sera all reacted on immunofluorescence study for M2 antibodies and on immunoblotting with the pyruvate dehydrogenase complex E2 subunit from each of the three enzymes, but there were strikingly different inhibitory capacities. The primary biliary cirrhosis sera were highly inhibitory for mammalian pyruvate dehydrogenase complex (10 of 10 inhibitory; mean level of inhibition, 99%), moderately inhibitory for yeast pyruvate dehydrogenase complex (10 of 10 inhibitory; mean level, 70%) and weakly inhibitory for Escherichia coli pyruvate dehydrogenase complex (4 of 10 inhibitory; mean level, 26%). Thus, with a functional assay that depends on epitope recognition of primary biliary cirrhosis sera, cross-reactivity between mammalian and bacterial pyruvate dehydrogenase complex enzymes is low and molecular mimicry, at least at the B-lymphocyte level, is not supported.
authors.affiliation: Centre For Molecular Biology and Medicine, Monash University, Clayton, Australia.
authors.forename: K L
authors.initials: KL
authors.lastname: Teoh
authors.forename: I R
authors.initials: IR
authors.lastname: Mackay
authors.forename: M J
authors.initials: MJ
authors.lastname: Rowley
authors.forename: S P
authors.initials: SP
authors.lastname: Fussey
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D003429:Cross Reactions; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015151:Immunoblotting; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013045:Species Specificity; D013552:Swine
chemical_list: D001323:Autoantibodies; D007106:Immune Sera; D011768:Pyruvate Dehydrogenase Complex