AUTOANTIBODIES AGAINST SUBUNITS OF PYRUVATE-DEHYDROGENASE AND CITRATESYNTHASE IN A CASE OF PEDIATRIC BILIARY-CIRRHOSIS

In a newborn girl with a history of connatal liver damage, histologica l examination of a liver biopsy sample taken during the seventh week o f life revealed incipient destruction of bile ducts. Very high titres of antimitochondrial antibodies were later detected in the plasma. As the hepatic injury tended towards fibrosis, the histological diagnosis became primary biliary cirrhosis. Autoantibodies against E-1 alpha, E -2, and E-3 subunits and protein X component of pyruvate dehydrogenase complex, and against citrate synthase were detected on western immuno blotting in a 1 in 1000 dilution of the patient's serum. The patient d ied of her illness at 11 years of age. In liver specimens obtained at autopsy human immunoglobulin deposition was detected on the surface of almost all hepatic cells by immunohistology. As there is a physical a nd functional interaction between pyruvate dehydrogenase and citrate s ynthase within the mitochondria, the presence of autoantibodies agains t certain proteins in the patient suggests that in this form of the di sease the molecular recognition and then the autoimmunisation process could be directed against a mitochondrial enzyme cluster containing bo th pyruvate dehydrogenase and citrate synthase.