Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease -- possible association with a steroid-resistant transplant rejection episode.
OBJECTIVE
Antibodies to cytochrome P450 2D6, also known as 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.


CONCLUSIONS
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.
Lohse
A W
AW
1st Department of Medicine, Johannes Gutenberg-University, Mainz, Germany.
Obermayer-Straub
P
P
Gerken
G
G
Brunner
S
S
Altes
U
U
Dienes
H P
HP
Manns
M P
MP
Meyer zum Büschenfelde
K H
KH
D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology*; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D006527:Hepatolenticular Degeneration / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D013270:Stomach / Q000276:immunology / Q000473:pathology; D013997:Time Factors
D001323:Autoantibodies; D007166:Immunosuppressive Agents; C060729:anti-liver kidney microsome antibody; D016572:Cyclosporine; D011239:Prednisolone; D019389:Cytochrome P-450 CYP2D6; D001379:Azathioprine