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Characterization of the antigenicity of the formiminotransferase-cyclodeaminase in type 2 autoimmune hepatitis.

Abstract
Human formiminotransferase-cyclodeaminase (hFTCD) is the autoantigen recognized by anti-liver cytosol type 1 (LC1) autoantibodies in type 2 autoimmune hepatitis (AIH) patients. In rats, this octameric protein is localized on the Golgi apparatus and binds brain microtubules (MTs) and vimentin. Subcellular localization of human formiminotransferase-cyclodeaminase and its implication in the pathogenesis of autoimmune hepatitis are unknown. Localization of the human formiminotransferase-cyclodeaminase in human hepatocytes was done using indirect immunofluorescence and subcellular fractionations followed by in vitro binding techniques. The formiminotransferase-cyclodeaminase antigen at two distinct locations in hepatocytes, free in the cytosol and associated with the Golgi membranes are recognized by anti-liver cytosol type 1 autoantibodies. The human formiminotransferase-cyclodeaminase binds reversibly to the Golgi membranes and this complex formation is increased by anti-liver cytosol type 1 autoantibodies. Finally, human formiminotransferase-cyclodeaminase does not interact with liver-specific cytoskeleton proteins. Anti-liver cytosol type 1 autoantibodies are directed against the mature high molecular form of human formiminotransferase-cyclodeaminase. Therefore, the subcellular location of the protein may influence the production of autoantibodies and their role in the pathogenesis of type 2 autoimmune hepatitis. This antigen-driven response does not appear to be facilitated or enhanced by a possible interaction between human formiminotransferase-cyclodeaminase and hepatocyte cytoskeleton proteins.
AuthorsReginald Renous, Pascal Lapierre, Idriss Djilali-Saiah, Susana Vitozzi, Fernando Alvarez
JournalExperimental cell research (Exp Cell Res) Vol. 292 Issue 2 Pg. 332-41 (Jan 15 2004) ISSN: 0014-4827 [Print] United States
PMID14697341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • Autoantigens
  • Cytoskeletal Proteins
  • Ammonia-Lyases
  • formiminotetrahydrofolate cyclodeaminase
Topics
  • Ammonia-Lyases (immunology, metabolism)
  • Animals
  • Antibody Specificity (immunology)
  • Autoantibodies (immunology)
  • Autoantigens (immunology)
  • Cell Compartmentation (immunology)
  • Cell Line, Tumor
  • Cytoskeletal Proteins (immunology, metabolism)
  • Cytosol (immunology, metabolism)
  • Fluorescent Antibody Technique
  • Golgi Apparatus (immunology, metabolism)
  • Hepatitis, Autoimmune (enzymology, immunology)
  • Hepatocytes (cytology, enzymology, immunology)
  • Humans
  • Intracellular Membranes (immunology, metabolism)
  • Liver (enzymology, immunology, physiopathology)
  • Protein Binding (immunology)
  • Rabbits
  • Subcellular Fractions

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