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

Background & Aims: Anti-liver cytosol type 1 autoantibodies have been repor ted in association with anti-liver-kidney microsome type 1 autoantibodies i n 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti- liver cytosol type 1 antibodies are the only liver-related circulating auto antibodies. The liver cytosol antigen is a liver-specific 62-kilodalton pro tein present in the cell as an oligomer of similar to 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cyto sol antibody. Methods: To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementar y DNA library from HepG2 cells. Double immunodiffusion method was used to s how the identity between the cytosolic and the cloned protein. Results: The sequence of two isolated clones showed 85.2% homology with the formiminotr ansferase 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 immu noblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD. Conclusions: This enzyme is a liver-specific antigen rec ognized by the sera of patients with autoimmune hepatitis.