Hepatic and biliary Autoantigens

Abstract

Chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC) are two enigmatic liver diseases in which autoimmunity is implicated. Provisional criteria to separate the autoimmune type of CAH (A-CAH) from others are specified. Western immunoblotting using disease sera and antibody screening of a rat liver gene expression library were used to identify hepatic and biliary autoantigens relevant to the pathogenesis of A-CAH or PBC. With all reported putative liver-specific autoantigen preparations, serum reactivity in A-CAH and CAH due to infection with hepatitis B virus tends to be similar. In A-CAH, immunoblotting showed multiple reactivities with all liver preparations used, including hepatocyte membrane. In PBC, immunoblotting showed two disease-specific polypeptide antigens of MW 70 and 45 kD. A cDNA clone derived from a rat liver gene expression library was shown to encode the antigenic site of the 70 kD polypeptide. Recently published work in two other laboratories has established that the 70 kD autoantigen is the E2 component of the pyruvate dehydro-genase enzyme (PDH), and a proposed antibody-binding site (autoepltope) is a conserved decapeptide, corresponding to residues 83–92 of the deduced amino acid sequence of M2, which is the binding site of lipoic acid to the E2 component of PDH.