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

Abstract

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 E1alpha subunit of the pyruvate dehydrogenase complex (PDH) also have been found, but those against the E1alpha subunit of branched-chain 2-oxo acid dehydrogenase complex (BCKADH) have not been detected. We investigated the occurrence of BCKADH-E1alpha-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-E1alpha, and these same sera also reacted with BCKADH-E2. No PBC sera reacted with BCKADH-E1beta. The reactivity of PBC sera with BCKADH-E1alpha was removed only when the sera were pre-absorbed with this antigen. However, reactivities to BCKADH-E2 and PDH-E1alpha were retained. Affinity-purified antibodies to BCKADH-E1alpha reacted with BCKADH-E1alpha, but not PDH-E1alpha. Thus, it was confirmed that anti-BCKADH-Elalpha did not cross-react with either BCKADH-E2 or PDH-E1alpha.

CONCLUSIONS:

BCKADH-E1alpha-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.

• Authors: T Mori, K Ono, M Hakozaki, R Kasukawa, H Kochi
• Journal: Journal of hepatology (J Hepatol) Vol. 34 Issue 6 Pg. 799-804 (Jun 2001) ISSN: 0168-8278 [Print] Netherlands
• PMID: 11451161 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Autoantigens
• Multienzyme Complexes
• Protein Subunits
• Pyruvate Dehydrogenase Complex
• Ketone Oxidoreductases
• 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

Topics

• 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
• Animals
• Antibody Specificity
• Autoantibodies (blood, isolation & purification)
• Autoantigens (chemistry)
• Case-Control Studies
• Cattle
• Cross Reactions
• Enzyme-Linked Immunosorbent Assay
• Humans
• Immunoblotting
• Ketone Oxidoreductases (chemistry, immunology)
• Liver Cirrhosis, Biliary (enzymology, immunology)
• Mitochondria, Liver (enzymology, immunology)
• Multienzyme Complexes (chemistry, immunology)
• Protein Subunits
• Pyruvate Dehydrogenase Complex (chemistry, immunology)