Cytochrome P450IA2 and aromatic L-amino acid decarboxylase are hepatic autoantigens in autoimmune polyendocrine syndrome type I.
Autoimmune chronic active hepatitis (AI-CAH) is a feared component of autoimmune polyendocrine syndrome type I (APS I). In this study, immunoreactivity was assessed in sera from eight APS I patients, of whom three had AI-CAH, in an attempt to identify hepatic autoantigens. We performed indirect immunofluorescence staining of human and rat liver sections, Western blots on subcellular fractions of human and rat liver, immunoprecipitations of labelled aromatic L-amino acid decarboxylase (AADC) and cytochrome P450IA2 (CYP IA2) expressed by an in vitro transcription and translation system and studies of enzymatic activity. Autoantibodies against AADC were present in sera from all eight APS I patients, while immunoreactivity against CYP IA2 was only found in sera from the three APS I patients with AI-CAH. Enzymatic activity of CYP IA2 was inhibited by sera from APS I patients with AI-CAH but not by control sera. Our results show that CYP IA2 and AADC constitute hepatic autoantigens in patients with APS I and that immunoreactivity against CYP IA2 is associated with the presence of AI-CAH.
Gebre-Medhin
G
G
Department of Internal Medicine, University Hospital, Uppsala University, Sweden. gennet.gebre-medhin@medicin.uu.se
Husebye
E S
ES
Gustafsson
J
J
Winqvist
O
O
Goksøyr
A
A
Rorsman
F
F
Kämpe
O
O
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000032:analysis* / Q000276:immunology; D015153:Blotting, Western; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000276:immunology*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019084:Fluorescent Antibody Technique, Indirect; D006521:Hepatitis, Chronic / Q000276:immunology; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000276:immunology*; D008862:Microsomes, Liver / Q000201:enzymology; D016884:Polyendocrinopathies, Autoimmune / Q000201:enzymology* / Q000276:immunology; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D051381:Rats; D013347:Subcellular Fractions / Q000737:chemistry; D014158:Transcription, Genetic
D001323:Autoantibodies; D001324:Autoantigens; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019388:Cytochrome P-450 CYP1A2; D001142:Aromatic-L-Amino-Acid Decarboxylases