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Are antimitochondrial antibodies in primary biliary cirrhosis induced by R(rough)-mutants of enterobacteriaceae?
R Stemerowicz1, U Hopf, B Möller
1Medizinische Klinik, Universitätsklinikum Charlottenburg, Berlin, Federal Republic of Germany.
Abstract:
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.
Insights
Primary biliary cirrhosis (PBC) is linked to antibodies targeting mitochondria and gram-negative bacteria. These findings suggest a potential bacterial cause for PBC, offering new insights into liver disease origins.
Area of Science:
- Immunology
- Hepatology
- Microbiology
Background:
- Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial antibodies (AMA).
- The exact etiology of PBC remains unclear, although infectious or environmental triggers are suspected.
Purpose of the Study:
- To investigate the potential shared antigenic determinants between mitochondria and gram-negative bacteria in patients with PBC.
- To explore the hypothesis of a bacterial etiology for PBC.
Main Methods:
- Immunoblotting technique using mitochondria and gram-negative bacteria as antigens.
- Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for antigen separation.
- Absorption experiments and two-dimensional immunoblotting.
Main Results:
- PBC patients' sera recognized mitochondrial antigens (70 kD, 50 kD, 42 kD) and similar bands in Enterobacteriaceae (70-80 kD, 50-52 kD).
- PBC-specific mitochondrial antigens were recognized by antisera against specific bacterial mutants, not wild-type bacteria.
- Shared determinants between mitochondria and gram-negative bacteria were confirmed, particularly in bacterial mutants with defective polysaccharide synthesis.
Conclusions:
- Mitochondria and gram-negative bacteria share identical PBC-specific determinants.
- PBC-specific antigens appear to be expressed in gram-negative bacteria, potentially triggering autoimmunity in susceptible individuals.
- The findings support a hypothesis linking bacterial infections or components to the development of PBC.