IMMUNOREACTIVITY OF ANTIMITOCHONDRIAL AUTOANTIBODIES IN JAPANESE PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS

The incidence and prevalence of primary biliary cirrhosis show wide ge ographic differences, The frequency of this disease in Japan is lower than in Northern Europe. To elucidate the immunoreactivity of serum wi th enzymes of the 2-oxo-acid dehydrogenase complex (2-OADC) and the M2 mitochondrial antigenic complex in Japanese patients, we examined ser a from 107 patients with primary biliary cirrhosis from three geograph ically different regions of Japan, The sera were assayed by immunofluo rescence on frozen tissue sections, immunoblotting on bovine heart mit ochondria and recombinant E2 subunit of branched chain ore-acid dehydr ogenase complex (BCOADC-E2), ELISA using recombinant E2 subunit of hum an pyruvate dehydrogenase complex (PDC-E2) and purified porcine 2-oxog lutarate dehydrogenase complex (OGDC), and enzyme inhibition assay usi ng porcine PDC and OGDC. Of the 107 sera, 95 (88%) reacted by immunofl uorescence, 102 (95%) by immunoblotting with at least one of the M2 au toantigens, although only 78 (73%) reacted with PDC-E2; 72 (67%) by EL ISA with PDC-E2; and 81 (76%) with PDC by the enzyme inhibition assay. Thus, the frequency of reactivity with PDC-E2 by all assays was lower for Japanese than the reported frequency for Caucasian patients with primary biliary cirrhosis, whereas the frequency of reactivity by immu noblotting and ELISA against 2-OADC enzymes other than PDC was relativ ely higher. The relative frequency of reactivity of autoantibodies to the M2 autoantigens was similar for the three different regions of Jap an. The different autoantibody profiles for Japanese and Caucasian pat ients with primary biliary cirrhosis point to immunogenetic and enviro nmental determinants of this disease, which should provide new insight s into its autoimmune origins.