Are antimitochondrial antibodies in primary biliary cirrhosis induced by R(rough)-mutants of enterobacteriaceae?
Antimitochondrial antibody (AMA)-positive serum samples from 45 patients with primary biliary cirrhosis (PBC) and AMA-negative serum samples from patients with chronic liver diseases, systemic lupus erythematosus, or rheumatoid arthritis were studied by an immunoblot technique with mitochondria from bovine heart and pig kidney and with several strains of gram-negative bacteria as antigens after separation by sodiumdodecylsulphate polyacrylamide gel electrophoresis. Serum from patients with PBC recognised up to three mitochondrial antigens with molecular weights of 70 kD, 50 kD, and 42 kD. Equivalent patterns were found with bands at 70-80 kD and 50-52 kD with Enterobacteriaceae as antigens. AMA-reactive polypeptides were localised in the ribosomal and membrane fractions from Enterobacteriaceae but differed from known outer membrane proteins. Conversely, PBC-specific mitochondrial antigens at 70 kD and 50 kD were recognised by rabbit antisera against Salmonella minnesota Rb and Rc mutants but not by antisera against wild-type Enterobacteriaceae. Absorption experiments and two-dimensional immunoblotting studies confirmed that mitochondria and gram-negative bacteria share identical PBC-specific determinants. It seems that PBC-specific antigens are expressed in gram-negative bacteria and that these antigens may be immunogenic in mutants with defective polysaccharide synthesis. The data support the hypothesis of a bacterial aetiology for PBC.
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001426:Bacterial Proteins / Q000032:analysis; D004755:Enterobacteriaceae / Q000276:immunology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007123:Immunoelectrophoresis, Two-Dimensional; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology*; D008970:Molecular Weight; D009154:Mutation; D012269:Ribosomal Proteins / Q000032:analysis
D001323:Autoantibodies; D001426:Bacterial Proteins; D012269:Ribosomal Proteins