HALOTHANE HEPATITIS PATIENTS HAVE SERUM ANTIBODIES THAT REACT WITH PROTEIN DISULFIDE-ISOMERASE

Clinical and laboratory evidence suggests that the fulminant liver fai lure sometimes associated with the inhalation anesthetic halothane may be an immune-mediated toxicity. Most importantly, the vast majority o f patients with a clinical diagnosis of halothane hepatitis have serum antibodies. which react with one or more specific liver microsomal pr oteins that have been covalently altered by the trifluoroacetyl chlori de metabolite of halothane. The serum antibodies are specific to halot hane hepatitis patients and are not seen in sera of patients with othe r types of liver pathology. In this study, a 57-kD trifluoroacetylated liver microsomal neoantigen associated with halothane hepatitis and n ative 57-kD protein were purified from liver microsomes of halothane-t reated and -untreated rats, respectively. When the purified trifluoroa cetylated 57-kD and native 57-kD proteins were used as test antigens i n an enzyme-linked immunosorbent assay, serum antibodies from halothan e hepatitis patients (n = 40) reacted with both of these proteins to a significantly greater extent than did serum antibodies from control p atients (n = 32). On the basis of its apparent monomeric molecular mas s, isoelectric point and NH2-terminal amino acid and tryptic peptide s equences. the 57-kD protein has been identified as rat liver protein d isulfide isomerase. Antibodies raised against rat liver protein disulf ide isomerase also reacted with a protein of approximately 58-kD in hu man liver microsomes. The results of this investigation suggest that t rifluoroacetylated protein disulfide isomerase is one of the immunogen s associated with halothane hepatitis. In certain patients it might le ad either to specific antibodies or, possibly, to specific T cells, wh ich could be responsible for halothane hepatitis.