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

• Published in: Journal of hepatology 1999-07, Vol.31 (1), p.149-155
• Main Authors: Lohse, Ansgar W, Obermayer-Straub, Petra, Gerken, Guido, Brunner, Silvia, Altes, Ulrich, Dienes, Hans Peter, Manns, Michael P, Büschenfelde, Karl-Hermann Meyer zum
• Format: Article
• Language: English
• Subjects: Adult; Antibody Specificity; Autoantibodies - analysis; Azathioprine - therapeutic use; Biological and medical sciences; Cyclosporine - therapeutic use; Cytochrome P-450 CYP2D6 - immunology; Cytochrome P450 2D6; Drug Resistance; Enzyme-Linked Immunosorbent Assay; Graft Rejection - drug therapy; Graft Rejection - immunology; Hepatolenticular Degeneration - surgery; Humans; Immunosuppressive Agents - therapeutic use; Kidney - immunology; Kidney - pathology; Liver transplantation; Liver Transplantation - immunology; Liver Transplantation - pathology; Liver, biliary tract, pancreas, portal circulation, spleen; LKM-autoantibodies; Male; Medical sciences; Prednisolone - therapeutic use; Stomach - immunology; Stomach - pathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Time Factors; Transplant rejection; Wilson's disease
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(99)80175-5

Background/Aims: Antibodies to cytochrome P450 2D6, also knownas LKM1-autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis C. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for 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 transplantation 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. The serum of the organ donor was also tested. Results: All the sera prior to transplantation and up to 4 months after transplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed LKM antibodies at high titre (70% in inhibition ELISA) and has remained positive since (now more than 4 years). Reactivity was exclusively to the cytochrome isoenzyme 2D6. Hepatitis C infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor serum was negative for all autoantibodies and for hepatitis C and G virus infection. Discussion: We here describe a patient developing LKM1-autoantibodies without evidence of autoimmune or viral hepatitis. The close temporal association with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.