AMA are a heterogeneous group of autoantibodies directed against various proteins located in the outer and inner membrane of mitochondria (Table 12).

Table 12 AMA subtypes

Their distinct target antigens are formed in the tissues. Non-organ-specific subtypes of antibodies have been described besides those antibodies which exhibit a relatively high organ specificity.
Using fluorescence techniques with slices from different organs, i.e. liver, stomach, kidney, heart and pancreas, the mitochondria autoantibodies of different specificity can be discriminated. For some of the AMA subtypes their specific target protein yet remains unclear. Specific antimitochondrial 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). AMA detected by IFA using HEP-2 monolayers are mostly AMA-M2 autoantibodies. AMA-M2 should be verified by ELISA allowing also a follow-up after diagnosis because of their high sensitivity and specificity (175). In contrast, ANCA immunofluorescence patterns are not influenced by AMA-M2 (176).

In patients with other autoimmune diseases determination of AMA antibodies allows an early screening for the occurrence of subtype M2 and M9 antibodies which may be related with the development and/or association of PBC. Subtyping of AMA allows an immunological and prognostic classification of PBC. Beginning cases of symptomatic PBC often exhibit only AMA-M2 (sometimes in combination with AMA-M9), whereas progressive cases and mixed syndromes with chronic acute hepatitis are related with the occurrence of AMA- M2, -M4 and -M8 antibody subtypes (177).