Open AccessSera from patients with tuberculosis recognize the M2a‐epitope (E2‐subunit of pyruvate dehydrogenase) specific for primary biliary cirrhosis
Author(s) -
KLEIN R.,
WIEBEL M.,
ENGELHART S.,
BERG P. A.
Publication year - 1993
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1993.tb03397.x
Subject(s) - primary biliary cirrhosis , pyruvate dehydrogenase complex , epitope , immunology , protein subunit , medicine , biliary cirrhosis , tuberculosis , biology , antibody , enzyme , autoimmune disease , pathology , biochemistry , gene
SUMMARY 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.