Characterization of the antigenicity of the formiminotransferase-cyclodeaminase in type 2 autoimmune hepatitis.
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.
Renous
Reginald
R
Service de Gastroentérologie et Nutrition, Hôpital Sainte-Justine, Montreal, Quebec, Canada H3T 1C5.
Lapierre
Pascal
P
Djilali-Saiah
Idriss
I
Vitozzi
Susana
S
Alvarez
Fernando
F
D000642:Ammonia-Lyases / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002451:Cell Compartmentation / Q000276:immunology; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000276:immunology / Q000378:metabolism; D019693:Hepatitis, Autoimmune / Q000201:enzymology / Q000276:immunology*; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007425:Intracellular Membranes / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology; D011485:Protein Binding / Q000276:immunology; D011817:Rabbits; D013347:Subcellular Fractions
D001323:Autoantibodies; D001324:Autoantigens; D003598:Cytoskeletal Proteins; D000642:Ammonia-Lyases; C020148:formiminotetrahydrofolate cyclodeaminase