title: LKM-1 sera from autoimmune hepatitis patients that recognize ERp57, carboxylesterase 1 and CYP2D6.
abstract: Liver kidney microsomal antibody type 1 (LKM-1) is a diagnostic marker for autoimmune hepatitis type 2 (AIH-2). Characterization of LKM autoantibodies of patients with AIH-2 demonstrated that a proportion of LKM sera contains autoantibodies which recognize one or more small linear epitopes on cytochrome P450, CYP2D6, an enzyme of drug metabolism pathways. The identification and epitope mapping of antigens involved in autoimmune diseases are important in understanding the mechanisms triggering autoimmunity and providing guidance for designing immunomodulatory therapy. In this study, several proteins recognized by LKM-1-positive sera in rat and human hepatic microsomes were analyzed by MALDI-TOF-MS after separation with ion-exchange chromatography or two-dimensional polyacrylamide gel electrophoresis. We identified these proteins as ERp57 and carboxylesterase 1 (CES1) as well as CYP2D6. Epitopes in ERp57 and CES1 recognized by LKM-1-positive serum were investigated by enzyme-linked immunosorbent assay (ELISA) with protease-digested peptides of ERp57 and CES1. The peptides comprising amino acids 105-129 of ERp57 and 558-566 of CES1 were specifically recognized by the serum. The epitopes in EPp57 and CES1 recognized by LKM-1-positive sera were homologous with those in hepatitis C virus (HCV). Viral infection of such as HCV may thus possibly trigger autoimmune hepatitis.
authors.affiliation: Nanobiotechnology Research Center and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda 669-1337, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Komurasaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Imaoka
authors.forename: Naomichi
authors.initials: N
authors.lastname: Tada
authors.forename: Kazushi
authors.initials: K
authors.lastname: Okada
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Funae
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002265:Carboxylic Ester Hydrolases / Q000276:immunology*; D002460:Cell Line; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry; D018937:Hepatitis C Antibodies / Q000097:blood / Q000737:chemistry; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000276:immunology*; D006801:Humans; D008862:Microsomes, Liver / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D019704:Protein Disulfide-Isomerases / Q000276:immunology*; D051381:Rats
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D018937:Hepatitis C Antibodies; C060729:anti-liver kidney microsome antibody; D019389:Cytochrome P-450 CYP2D6; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human