High Levels of Autoantibodies against Drug-metabolizing Enzymes in SLA/LP-positive AIH-1 Sera

• Published in: Autoimmunity (Chur, Switzerland) Switzerland), 2004-09, Vol.37 (6-7), p.473-480
• Main Authors: Shinoda, Masakazu, Tanaka, Yuta, Kuno, Takuya, Matsufuji, Tamiko, Matsufuji, Senya, Murakami, Yasuko, Mizutani, Takaharu
• Format: Article
• Language: English
• Subjects: Adult; AIH, autoimmune hepatitis; Aryl Hydrocarbon Hydroxylases - immunology; ATP-Binding Cassette, Sub-Family B, Member 1 - immunology; Autoantibodies - blood; Autoantibody; Autoantigens - immunology; Autoimmune hepatitis; Biological and medical sciences; CYP; Cytochrome P-450 CYP2A6; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System - immunology; ELISA, enzyme-linked immuno-sorbent assay; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Glucuronosyltransferase - immunology; Hepatitis, Autoimmune - immunology; Humans; Immunopathology; Male; MDR1; Medical sciences; Microsomes, Liver - immunology; Middle Aged; Mixed Function Oxygenases - immunology; UDP-glucuronosyltransferase
• ISSN: 0891-6934; 1607-842X
• DOI: 10.1080/08916930400001891

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 23 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 2-22 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.