CLINICOPATHOLOGICAL STUDY OF PRIMARY BILIARY-CIRRHOSIS NEGATIVE FOR ANTIMITOCHONDRIAL ANTIBODIES

Primary biliary cirrhosis (PBC) is characterized by the occurrence of antimitochondrial antibodies (AMA) and the progressive destruction of intrahepatic bile ducts, followed by biliary cirrhosis. However, there are about 5% of PBC patients who show clinicopathological features of PBC but are negative for AMA. In this study, clinicopathological feat ures, as well as antibody reactivity against recombinant (r)-mitochond rial polypeptides, were examined in 30 AMA negative PBC patients and 3 8 AMA positive PBC patients, in whom the presence of AMA had been dete rmined by indirect immunofluorescence (IF). There were few differences in the clinical and serological features between both groups. Histopa thologic features, including staging, bile duct lesions and granuloma, were also similar in both groups. Among the 30 IF-tested AMA negative patients, 29 were also negative against beef heart mitochondrial prot eins, but 24 reacted to one or more of the following r-polypeptides, a s determined by immunoblotting: E1 alpha of pyruvate dehydrogenase com plex, the E2 subunit of pyruvate dehydrogenase complex, and the branch ed-chain 2-oxo-acid dehydrogenase complex. The remaining sx AMA-negati ve patients were asymptomatic, and histologically resembled having sta ge 1 of the disease, with relatively mild lymphocytic piecemeal necros is. One case was positive for anti-smooth muscle antibody. The other c linicopathological features of these patients were similar to those of other AMA negative patients. The present study found that a majority of the AMA-negative patients fulfilling other clinicopathological crit eria of PBC, had features similar to the AMA-positive PBC patients, an d that a majority of IF AMA-negative patients were positive for r-poly peptides of the 2-oxo-acid dehydrogenase complex. It seems that nearly all the AMA negative patients possess a broad spectrum of antibody pr ofile of AMA, in addition to clinicopathological and serological featu res.