Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease - possible association with a steroid-resistant transplant rejection episode

Background/Aims: Antibodies to cytochrome P450 2D6, also known as LKM1-auto antibodies, are characteristic for a subgroup of patients with autoimmune h epatitis, but can also occasionally be found in hepatitis C, We observed th e occurrence of LKM1-autoantibodies 4 months after liver transplantation fo r Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis C. Methods: Sera from several time points prior to and following transplantati on were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting, Antigen specificity was confirmed by Western blotting analysis on different cytochrome P450 isoenzymes. The absence of viral hepatitis C and hepatitis G virus infection was confirmed by polymerase chain reaction, Th e serum of the organ donor was also tested. Results: All the sera prior to transplantation and up to 4 months after tra nsplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed L KM antibodies at high titre (70% in inhibition ELISA) and has remained posi tive since (now more than 4 years). Reactivity was exclusively to the cytoc hrome isoenzyme 2D6. Hepatitis C infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor seru m was negative for all autoantibodies and for, hepatitis C and G virus infe ction. Discussion: We here describe a patient developing LKM1-autoantibodies witho ut evidence of autoimmune or viral hepatitis. The close temporal associatio n with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.