DETECTION AND CHARACTERIZATION OF LIVER MEMBRANE AUTOANTIBODIES IN CHRONIC ACTIVE HEPATITIS BY A SOLID-PHASE RADIOIMMUNOASSAY

Abstract

A solid-phase radioimmunoassay was developed to detect antibodies to liver membrane antigens in sera of patients with HBsAg[hepatitis B surface antigen]-negative and -positive liver diseases and primary non-hepatic autoimmune diseases. Of 14 patients, 10 with HBsAg-negative CAH [chronic active hepatitis] had autoantibodies detected by RIA [radioimmunoassay]; negative results were obtained with sera of 7 patients with HBsAg-positive acute and chronic liver diseases, 6 patients with miscellaneous liver diseases, including 2 patients with PBC [primary biliary cirrhosis], 2 healthy blood donors and 7 patients with primary non-hepatic autoimmune diseases. Antibodies detected by RIA correlated with liver membrane autoantibodies (LMA) found by indirect immunofluorescence; no correlation was observed with AMA [anti-mitochondrial antibodies], ANA [anti-nuclear antibodies] and SMA [smooth muscle antibodies]. Species-cross-reacting antibodies could be absorbed by preincubation with isolated plasma cell membranes prepared from rabbit livers. Liver membrane autoantibodies detected by RIA were directed against 3 different antigen fractions obtained from Sepharose 6B chromatography including LSP [liver-specific membrane antigen] and LM-Ag [liver membrane antigen]. Only 3 of 10 antibodies were directed against species-specific determinants; others cross-reacted with rabbit antigens. Only the antibody to LSP was organ-specific, all others cross-reacted with kidney proteins. Ferritin, human serum albumin and human plasma lipoprotein were excluded as target antigens. Although several sera reacted with identical molecules, a remarkable heterogeneity of liver membrane autoantibodies was observed.