Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis

Gastroenterology. 1999 Mar;116(3):643-9. doi: 10.1016/s0016-5085(99)70186-1.

Abstract

Background & aims: Anti-liver cytosol type 1 autoantibodies have been reported in association with anti-liver-kidney microsome type 1 autoantibodies in 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti-liver cytosol type 1 antibodies are the only liver-related circulating autoantibodies. The liver cytosol antigen is a liver-specific 62-kilodalton protein present in the cell as an oligomer of approximately 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cytosol antibody.

Methods: To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementary DNA library from HepG2 cells. Double immunodiffusion method was used to show the identity between the cytosolic and the cloned protein.

Results: The sequence of two isolated clones showed 85.2% homology with the formiminotransferase cyclodeaminase (FTCD) enzyme from pig liver. Antibodies purified by affinity with the recombinant protein and sera from mice immunized with FTCD recognized a 62-kilodalton human cytosolic protein when tested by immunoblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD.

Conclusions: This enzyme is a liver-specific antigen recognized by the sera of patients with autoimmune hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Ammonia-Lyases / chemistry
  • Ammonia-Lyases / genetics
  • Ammonia-Lyases / immunology*
  • Animals
  • Antibodies, Monoclonal
  • Autoantibodies / blood*
  • Autoantigens / chemistry
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Base Sequence
  • Carcinoma, Hepatocellular
  • Cloning, Molecular
  • Cytosol / enzymology
  • Cytosol / immunology
  • Female
  • Gene Library
  • Glutamate Formimidoyltransferase
  • Hepatitis, Autoimmune / blood*
  • Hepatitis, Autoimmune / immunology
  • Humans
  • Immunodiffusion
  • Liver / enzymology*
  • Liver / immunology
  • Liver Neoplasms
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Multifunctional Enzymes
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Swine
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Autoantigens
  • Multienzyme Complexes
  • Multifunctional Enzymes
  • Recombinant Proteins
  • FTCD protein, human
  • Ftcd protein, mouse
  • Glutamate Formimidoyltransferase
  • Ammonia-Lyases
  • formiminotetrahydrofolate cyclodeaminase