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.
