Sera from patients with tuberculosis recognize the M2a-epitope (E2-subunit of pyruvate dehydrogenase) specific for primary biliary cirrhosis


Professor Dr P. A. Berg, Department of Internal Medicine, University of Tubingen, Otfried Müller Str, W-7400 Tubingen, Germany.


Anti-M2 antibodies in primary biliary cirrhosis (PBC) have been shown to react with the alpha-ketoacid dehydrogenase complex of the inner mitochondria! membrane consisting of six epitopes (E2 subunit of the pyruvate dehydrogenase complex (PDC). 70 kD; protein X of the PDC, 56 kD; alpha-ketoglutarate dehydrogenase complex, 52 kD; branched-chain alpha-kctoacid dehydrogenase, 52 kD; Elalpha subunit of PDC, 45 kD; and Elbeta-subunit of PDC, 36 kD). These epilopes 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 target epitope which is recognized by about 85% of all PBC sera. However, analysing sera from 28 patients with active pulmonary tuberculosis it became 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 rccombinant PDC-E2. In contrast, only two of 82 patients with other bacterial and viral infections including 25 patients with Escherichia coli infections reacted with the PBC-specific epilope at 70 kD. Naturally occurring mitochondrial antibodies (NOM A) were present in 54% of the patients with tuberculosis and in 50% of patients with other infectious disorders. They recognized cither a determinant at 65 kD (epsilon) or at 60/55 kD (zeta/eta).None of the sera from 100 blood donors had anti-M2 but 14 had NOM A. Testing anti-M2 and NOMA-positive marker sera by Western blotting against membrane fractions derived from mycobacteria and E. coli it could be shown that-like mammalian mitochondria—they contain both the PBC-specific M2 antigen as well as the non-PBC-specific naturally occurring mitochondrial antigen system (NOM Ag). The observation that PBC-specific antibodies were preferentially induced in patients suffering from a mycobactcrial infection may provide some new clues to the still unknown etiology of PBC.