Primary Biliary Cirrhosis
The M2 autoantigen is a major target of antimitochondrial autoantibodies (AMA), a characteristic serological feature in patients suffering from primary biliary cirrhosis (PBC). PBC is a severe autoimmune liver disease accompanied by destruction of intrahepatic bile ducts.
Molecular definition of the M2 antigen has shown it to be made up of at least 3 separate target proteins, the functionally similar so-called E2 subunits (or dihydrolipoamide transferases) of different mitochondrial dehydrogenase complexes:
pyruvate dehydrogenase complex (PDC-E2; approx. 60 kDa)
branched chain 2-oxo-acid dehydrogenase complex (BCOADC-E2; approx. 47 kDa)
2-oxoglutarate dehydrogenase complex (OGDC-E2; approx. 42 kDa).
Biochemically, these complexes catalyze the oxidative decarboxylation of various alpha-keto-acid substrates and mechanistically employ a prosthetic lipoamide group; they are located in the mitochondrial matrix in association with the inner membrane.
The most common reactivity of AMA positive PBC sera is against PDC-E2. Whereas some patients have AMA that react with PDC-E2 alone (95%), most patients also show reactivity against OGDC-E2 (39-88%) and/or BCOADC-E2 (53-55%). In fact, patients can be found with reactivity only against OGDC-E2 and/or BCOADC-E2 and no PDC-E2 autoantibodies (this PDF file shows examples that were obtained with DIARECTs recombinant E2 antigens). These patients will be missed in assays based on natural source-derived, predominantly PDC-E2-containing M2 antigen preparations.