Antibody binding and inhibition of pyruvate dehydrogenase (PDH) in sera from patients with primary biliary cirrhosis.

Autoantibodies reactive against mitochondria which are present in sera from patients with primary biliary cirrhosis (PBC) have been shown to bind to the lipoamide acetyltransferase moiety (E2) of the pyruvate dehydrogenase enzyme complex (PDH). This newly described antigen has been shown to be identical to M2, a 70-kD antigen of the inner mitochondrial membrane. Sera from 10 patients with PBC, 11 patients with chronic active hepatitis (CAH), 20 healthy controls and patients with thyroiditis and systemic lupus erythematosus (SLE) were tested by ELISA for the presence of antibodies (IgG and IgM classes and IgG subclasses) reactive against PDH. The effect of serum and separated IgG and IgM on the PDH enzyme activity was measured spectrophotometrically. Nine out of 10 PBC sera were positive by immunofluorescence for mitochondria (M2 pattern). These nine sera reacted strongly with both IgG and IgM to PDH in the ELISA and also inhibited the enzyme activity by 80% (s.d. 25%). This was significantly different compared with the controls (4 +/- 6%; P less than 0.001). Enzyme inhibition was mainly caused by IgG. Of all control sera (from healthy and patient individuals) only one patient with CAH reacted significantly in the tests. This CAH patient had a high antibody titre against mitochondria as measured by immunofluorescence.