title: High levels of autoantibodies against drug-metabolizing enzymes in SLA/LP-positive AIH-1 sera.
abstract: Autoimmune hepatitis type 1 (AIH-1) is characterized by the detection of smooth muscle autoantibodies, antinuclear antibodies and antineutrophil cytoplasmic autoantibodies, and AIH-2 is characterized by the presence of autoantibodies against LKM, which contain drug-metabolizing enzymes. In this study, we measured the levels of drug-metabolizing enzymes in AIH-1 patients (ANA-positive). We exhaustively investigated the level of autoantibodies against major CYPs and UDP-glucuronosyltransferases of typical phase II drug-metabolizing enzymes, a transporter (MDR1), and NADPH-cytochrome P450 reductase in 4 patients with AIH-1 and 6 controls, as a case report. Two (Patients 3 and 4) of the AIH patients exhibited high levels of autoantibodies, while two (Patients 1 and 2) of the patients and the controls did not. The levels of autoantibodies against CYP2C19, CYP2D6, CYP2E1, UGT1A6 and human liver microsomes in Patients 3 and 4 sera were over 2(3) times the levels in Patient 1, Patient 2 and the control sera. Meanwhile, the levels of autoantibodies against CYP1A2, CYP2A6, CYP2C9, UGT2B7, MDR1 and NADPH-cytochrome P450 reductase were 2-2(2) higher in Patients 3 and 4 than in the other subjects. We found that the pattern of elevation in the Patient 3 serum was not parallel with that in Patient 4. Thus, we found high levels of autoantibodies against drug-metabolizing enzymes in AIH-1 patients.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinoda
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuno
authors.forename: Tamiko
authors.initials: T
authors.lastname: Matsufuji
authors.forename: Senya
authors.initials: S
authors.lastname: Matsufuji
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Takaharu
authors.initials: T
authors.lastname: Mizutani
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D065637:Cytochrome P-450 CYP2A6; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014453:Glucuronosyltransferase / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000276:immunology; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000276:immunology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001323:Autoantibodies; D001324:Autoantigens; C046431:liver antigen LA-1; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D014453:Glucuronosyltransferase