ANTI-LIVER-KIDNEY MICROSOME-1 AUTOANTIBODY IN HCV-POSITIVE SERA REACTS PREDOMINANTLY TO CONFORMATIONAL EPITOPE, NOT TO LINEAR EPITOPE

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 ident ified. To determine whether these antigenic epitopes have conformation al or linear structure, the reactivity to full-length recombinant CYP2 D6 fusion protein and to four synthetic peptides spanning these four a ntigenic epitopes on CYP2D6 cDNA was investigated by enzyme-linked imm unosorbent assay. A total of 23 sera. positive for anti-LKM-1 by indir ect immunofluorescence were studied. Nine sera were negative for anti- HCV antibody and HCV-RNA and the remaining 14 sera were positive for a nti-HCV antibody and HCV-RNA. All sera reacted to full-length recombin ant CYP2D6 fusion protein. Reactivity to synthetic peptide (aa 257-270 ), which includes the main epitope on CYP2D6 to anti-LKM-1, was signif icantly 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 c onformational epitope and not to the linear epitope. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.