SERUM ANTIBODIES FROM HALOTHANE HEPATITIS PATIENTS REACT WITH THE RATENDOPLASMIC-RETICULUM PROTEIN-ERP72

Immunoblotting studies have previously shown that serum antibodies fro m halothane hepatitis patients react with several liver microsomal pro teins that have been modified by the trifluoroacetyl halide metabolite of halothane. In this study, an 80-kDa protein recognized by the pati ents' antibodies has been purified from rat liver microsomes and chara cterized. When the purified trifluoroacetylated 80-kDa and native 80-k Da proteins were employed as test antigens in an enzyme-linked immunos orbent assay, serum antibodies from halothane hepatitis patients react ed with both of these proteins to a significantly greater extent than did serum antibodies from control patients. Amino acid sequence analys es of several hydrolytic peptide fragments of the 80-kDa protein showe d that the protein was 99 % identical to the deduced amino acid sequen ce of a murine cDNA of the luminal endoplasmic reticulum protein ERp72 . These results indicate that trifluoroacetylated ERp72 in the liver o f halothane hepatitis patients may induce immune responses against epi topes present on the covalently altered protein and those present on t he native protein and may have a role in halothane hepatitis. In addit ion, immunoblot and immunohistochemical studies revealed that the 80-k Da protein was present in all tissues studied, but was in highest conc entration in liver, adipose tissue, ovaries, and testes and was enrich ed in specific cells of some organs. In the future, these findings sho uld help define the physiological function of ERp72.