ABSTRACT
In the last decade, the cloning and biochemical identification of mitochondrial autoantigens
in primary biliary cirrhosis (PBC) as members of the 2-oxoacid dehydrogenase complex
has greatly advanced the detection of antimitochondrial antibodies (AMA) and the understanding
of the immunobiology of the disease. Here, we discuss the methods of detecting AMA
and its isotypes, methods of epitope mapping, and using these methods in PBC liver
immunohistochemistry and Ig gene usage. Increasing evidence, including the specific
association of AMA with PBC, the unique similar but noncross-reactive conformational
epitope of the lipoyl domains of the mitochondrial autoantigens, the specific binding
of anti-PDC-E2 monoclonal antibodies and human combinatorial antibodies derived from
PBC patients to the apical area of bile duct epithelial cells in PBC livers, and Ig
gene usage of AMA, suggests that AMA is not an epiphenomenon of the disease but plays
a significant role in the patho gene sis of PBC.
KEY WORDS
2-oxo-acid dehydrogenase complex - epitope - bile duct epithelium - PDC-E2 - cross-reactive
molecule - Ig gene
