Autoantibodies of sera from patients with primary biliary cirrhosis recognize the α subunit of the decarboxylase component of human branched-chain 2-oxo acid dehydrogenase complex

Background/Aims: The major antigens for anti-mitochondrial autoantibodies in primary biliary cirrhosis (PBC) are the lipoyl-containing components of 2-oxo acid dehydrogenase complexes. Autoantibodies against the E1α subunit of the pyruvate dehydrogenase complex (PDH) also have been found, but those against the E1α subunit of branched-chain 2-oxo acid dehydrogenase complex (BCKADH) have not been detected. We investigated the occurrence of BCKADH-E1α-specific autoantibodies by employing the purified human antigen. Methods: The reactivities of PBC sera against purified antigens were assessed by ELISA and by immunoblotting analysis. The specificity of immunoreactivity was confirmed by absorption tests and affinity-purified antibodies. Results: Fourteen out of 27 PBC sera reacted with BCKADH-E1α, and these same sera also reacted with BCKADH-E2. No PBC sera reacted with BCKADH-E1β. The reactivity of PBC sera with BCKADH-E1α was removed only when the sera were pre-absorbed with this antigen. However, reactivities to BCKADH-E2 and PDH-E1α were retained. Affinity-purified antibodies to BCKADH-E1α reacted with BCKADH-E1α, but not PDH-E1α. Thus, it was confirmed that anti-BCKADH-E1α did not cross-react with either BCKADH-E2 or PDH-E1α. Conclusions: BCKADH-E1α-specific autoantibodies were found in the sera of PBC patients. The antibodies seem to occur subsequent to the anti-BCKADH-E2 antibody production, supporting the concept of intermolecular determinant spreading.