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.