Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis.
OBJECTIVE
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.
Service de Gastroentérologie et Nutrition, Hôpital Sainte-Justine, Montréal, Québec, Canada.
P
P
Lapierre
O
O
Hajoui
J C
JC
Homberg
F
F
Alvarez
D000595:Amino Acid Sequence; D000642:Ammonia-Lyases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology / Q000276:immunology; D005260:Female; D015723:Gene Library; D051042:Glutamate Formimidoyltransferase; D019693:Hepatitis, Autoimmune / Q000097:blood* / Q000276:immunology; D006801:Humans; D005779:Immunodiffusion; D008099:Liver / Q000201:enzymology* / Q000276:immunology; D008113:Liver Neoplasms; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D064251:Multifunctional Enzymes; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013552:Swine; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D009097:Multienzyme Complexes; D064251:Multifunctional Enzymes; D011994:Recombinant Proteins; C494848:FTCD protein, human; C494850:Ftcd protein, mouse; D051042:Glutamate Formimidoyltransferase; D000642:Ammonia-Lyases; C020148:formiminotetrahydrofolate cyclodeaminase