PRIMARY BILIARY-CIRRHOSIS - QUANTITATION OF AUTOANTIBODIES TO PURIFIED MITOCHONDRIAL-ENZYMES AND CORRELATION WITH DISEASE PROGRESSION

Primary biliary cirrhosis is characterized by the presence of antimitochondrial antibodies. Recently, six of the autoantigens have been identified as components. of the 2-oxo acid dehydrogenase multienzyme complexes located within mammalian mitochondria. Immunoblotting studies have shown that two of these components, namely E2 and protein X of pyruvate dehydrogenase complex, are the major antigenic polypeptides recognized by autoantibodies. This study shows the development of an enzyme-linked immunosorbent assay to detect and quantitate antibodies to these two purified antigens. Coded serum samples from 166 patients with primary biliary cirrhosis, 140 patients with other liver and/or autoimmune disease, and 52 normal women were analyzed for reactivity using this immunoassay. These results indicate that this rapid, simple method has a 93% sensitivity and 96% specificity in the diagnosis of primary biliary cirrhosis. The titer of immunoglobulin G autoantibodies correlated not only with antimitochondrial antibody titer measured by indirect immunofluorescence (P < 0.0001) but also with histological stage of disease (P < 0.04) and prognostic biochemical variables such as higher serum bilirubin and lower serum albumin levels (P = 0.038 and 0.028, respectively). There was no significant correlation between titer of autoantibodies and serum globulin or immunoglobulin G levels, indicating that the positive correlation with disease progression was not secondary to hypergammaglobulinemia. © 1990.