title: Autoantibody response to microsomal epoxide hydrolase in hepatitis C and A.
abstract: Autoimmune responses were observed in a large proportion of hepatitis C cases and are suspected to be part of viral pathogenesis. The AN6520 antigen (AN-Ag) is a normal cellular protein mainly expressed in liver that was found associated with non-A, non-B hepatitis. To elucidate its pathogenic role in hepatitis C, we developed an IgM capture assay using purified AN-Ag and confirmed that the antibody response to AN-Ag is associated almost exclusively with hepatitis C cases (29%). Screening of a human liver expression library revealed that AN-Ag is mainly the microsomal epoxide hydrolase (mEH), a drug-metabolizing enzyme that plays an important role in the metabolism of some mutagenic and carcinogenic epoxides. Using the purified recombinant human mEH as an antigen, we now found that antibodies against this protein are associated with nearly 82% of hepatitis C virus infections and surprisingly with 46% of patients with hepatitis A. The appearance of AN-Ag/mEH in the incubation period of hepatitis C as previously reported and the antibody responses shown here indicate that this enzyme may be a marker for or even a cause of some of the pathology associated with hepatitis C and A.
authors.affiliation: Department of Microbiology, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan. akatsuka@saitama-med.ac.jp
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Akatsuka
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Saito
authors.forename: Michiko
authors.initials: M
authors.lastname: Shindo
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kurokohchi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Hongying
authors.initials: H
authors.lastname: Duan
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Tsugikazu
authors.initials: T
authors.lastname: Komoda
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004851:Epoxide Hydrolases / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006506:Hepatitis A / Q000201:enzymology / Q000276:immunology*; D030041:Hepatitis A virus / Q000276:immunology*; D006526:Hepatitis C / Q000201:enzymology / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008113:Liver Neoplasms; D008566:Membranes / Q000201:enzymology / Q000276:immunology; D011863:Radioimmunoassay / Q000379:methods
chemical_list: D001323:Autoantibodies; D018076:DNA, Complementary; D018936:Hepatitis C Antigens; D007075:Immunoglobulin M; D004851:Epoxide Hydrolases