ASSOCIATION OF ANTI-58 KDA ENDOPLASMIC-RETICULUM ANTIBODIES WITH HALOTHANE HEPATITIS

We recently showed that when rats were administered the inhalation ane sthetic halothane, a 58 kDa liver endoplasmic reticulum protein became covalently trifluoroacetylated by the trifluoroacetyl chloride metabo lite of halothane. Although the 58 kDa protein showed 99% identity to that of the deduced amino acid sequence of a cDNA reported to correspo nd to phosphatidylinositol-specific phospholipase C-alpha, it did not have phosphatidylinositol-specific phospholipase C activity. It was co ncluded that the reported cDNA of phosphatidylinositol-specific phosph olipase C-alpha actually encoded for the 58 kDa endoplasmic reticulum protein of unknown function. Other researchers have come to the same c onclusion and have shown that the 58 kDa protein has protein disulfide -isomerase and protease activities. We now report that patients with h alothane hepatitis have serum antibodies that react with both purified trifluoroacetylated and native rat liver 58 kDa proteins. These resul ts suggest that when patients are exposed to halothane a human liver o rthologue of the rat liver trifluoroacetylated-58 kDa protein is forme d. In certain patients, this protein may become immunogenic and lead t o the formation of specific antibodies and or specific T-cells, which may react with both trifluoroacetylated and native 58 kDa proteins, an d ultimately be responsible, at least in part, for the hepatitis cause d by halothane.