SERA FROM PATIENTS WITH TUBERCULOSIS RECOGNIZE THE M2A-EPITOPE (E2-SUBUNIT OF PYRUVATE-DEHYDROGENASE) SPECIFIC FOR PRIMARY BILIARY-CIRRHOSIS

Anti-M2 antibodies in primary biliary cirrhosis (PBC) have been shown to react with the alpha-ketoacid dehydrogenase complex of the inner mi tochondrial membrane consisting of six epitopes (E2 subunit of the pyr uvate dehydrogenase complex (PDC), 70 kD; protein X of the PDC, 56 kD; alpha-ketoglutarate dehydrogenase complex, 52 kD; branched-chain alph a-ketoacid dehydrogenase, 52 kD; E1alpha subunit of PDC, 45 kD; and E1 beta-subunit of PDC, 36 kD). These epitopes are also present in the M2 fraction which is a chloroform extract from beef heart mitochondria. The E2 subunit of the PDC at 70 kD (M2a), especially, is a major targe t epitope which is recognized by about 85% of all PBC sera. However, a nalysing sera from 28 patients with active pulmonary tuberculosis it b ecame evident that 12 (43%) also recognized the PDC-E2 subunit (M2a), as shown by Western blotting using the M2 fraction, the purified PDC, and the recombinant PDC-E2. In contrast, only two of 82 patients with other bacterial and viral infections including 25 patients with Escher ichia coli infections reacted with the PBC-specific epitope at 70 kD. Naturally occurring mitochondrial antibodies (NOMA) were present in 54 % of the patients with tuberculosis and in 50% of patients with other infectious disorders. They recognized either a determinant at 65 kD (e psilon) or at 60/55 kD (zeta/eta).None of the sera from 100 blood dono rs had anti-M2 but 14 had NOMA. Testing anti-M2 and NOMA-positive mark er sera by Western blotting against membrane fractions derived from my cobacteria and E. coli it could be shown that-like mammalian mitochond ria-they contain both the PBC-specific M2 antigen as well as the non-P BC-specific naturally occurring mitochondrial antigen system (NOMAg). The observation that PBC-specific antibodies were preferentially induc ed in patients suffering from a mycobacterial infection may provide so me new clues to the still unknown etiology of PBC.