Description
Anti-mitochondrial antibodies (AMA) are a heterogeneous group of autoantibodies directed against various proteins that are located in the outer and inner membrane of mitochondria. Specific anti-mitochondrial antibodies have been described for the primary biliary cirrhosis (PBC) as subtypes M2, M4, M8 and M9. Other AMA subtypes are related to other diseases, like collagenosis (AMA-M5) and drug induced LE and Hepatitis (AMA-M3 and AMA-M6).
The heterogeneously reacting specific anti-mitochondrial antibodies of the M2 subtype are directed against three related proteins of the α-keto acid dehydrogenase complex which is located at the inside of the mitochondrial membrane. The recognized major epitope is located on the E2 subunit and the protein X of the pyruvate dehydrogenase complex (PDC). Additionally AMA-M2 autoantibodies recognise the (E1a und E1b) subunits of the same complex and the E2 subunit of several other multi enzyme complexes, such as the 2-oxo-glutarate dehydrogenase complex (OGDC) and the branched chain 2-oxo acid dehydrogenase complex (BCOADC).
Using HEp 2 Cell monolayers for indirect immune fluorescence AMA-M2 autoantibodies are characterised as a fine-speckled cytoplasmatic, perinuclear condensed fluorescence pattern. For differential diagnosis of the primary biliary cirrhosis (PBC) determination of AMA-M2 by ELISA is recommended because of its high sensitivity and specificity.
In patients with other autoimmune diseases determination of AMA antibodies allows an early screening for the occurence of subtype M2 and M9 antibodies which may be related with the development and / or association of PBC.
Profiling the AMA subtypes allows an immunological and prognostic classification of the primary biliary cirrhosis. Beginning cases of symptomatic PBC often exhibit only AMA-M2 sub-type antibodies (sometimes in combination with AMA-M9), whereas progressive cases and mixed syndromes with chronic acute hepatitis (CAH) are related with the occurrence of AMA-M2, -M4 and -M8 antibody subtypes