Anti-liver-kidney microsome-1 autoantibody in HCV-positive sera reacts predominantly to conformational epitope, not to linear epitope

Abstract

Anti-liver/kidney microsome (LKM)-1 autoantibody, which is a marker of autoimmune hepatitis type II, recognizes cytochrome P450IID6 (CYP2D6). Four major antigenic epitopes on CYP2D6 cDNA have already been identified. To determine whether these antigenic epitopes have conformational or linear structure, the reactivity to full-length recombinant CYP2D6 fusion protein and to four synthetic peptides spanning these four antigenic epitopes on CYP2D6 cDNA was investigated by enzyme-linked immunosorbent assay. A total of 23 sera, positive for anti-LKM-1 by indirect immunofluorescence were studied. Nine sera were negative for anti-HCV antibody and HCV-RNA and the remaining 14 sera were positive for anti-HCV antibody and HCV-RNA. All sera reacted to full-length recombinant CYP2D6 fusion protein. Reactivity to synthetic peptide (aa 257–270), which includes the main epitope on CYP2D6 to anti-LKM-1, was significantly more common in HCV-negative sera than in HCV-positive sera ( P<0.01). Anti-LKM-1 in HCV-positive sera reacts predominantly to the conformational epitope and not to the linear epitope.