Detection of an autoantibody directed against human liver microsomal protein in a patient with carbamazepine hypersensitivity.
A 16-year old patient with carbamazepine-induced hepatotoxicity, associated with the hypersensitivity manifestations of fever, rash and eosinophilia, is described. Mononuclear leucocytes from the patient were more sensitive to oxidative metabolites of carbamazepine generated by induced murine and human hepatic microsomes, than cells from controls. On immunoblot analysis, serum from the patient recognised a single protein band (94 kDa) on human liver microsomes, but none out of 25 control sera recognised this band. No bands were recognised by the patient serum on human kidney microsomes or on microsomes from mouse and rat liver.
Pirmohamed
M
M
Department of Pharmacology and Therapeutics, University of Liverpool.
Kitteringham
N R
NR
Breckenridge
A M
AM
Park
B K
BK
D000293:Adolescent; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D002220:Carbamazepine / Q000009:adverse effects* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology*; D003600:Cytosol / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000276:immunology*; D010634:Phenobarbital / Q000494:pharmacology; D011506:Proteins / Q000276:immunology*; D051381:Rats
D001323:Autoantibodies; D011506:Proteins; D002220:Carbamazepine; D010634:Phenobarbital