antimitochondrial autoantibodies

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There are several different types of mitochondrial antibodies (anti-mitochondrial antibodies (AMA)).

M2 anti-mitochondrial antibodies are found in 90-95% of patients with primary biliary cirrhosis (PBC). A titre of greater than 50 IU/ml suggests PBC even in the absence of symptoms and in the presence of normal alkaline phosphatase.

AMA that reacts with the E2 component of pyruvate dehydrogenase is diagnostic of PBC (1)

  • in 1967 it was demonstrated that PBC sera reacted in vitro with a trypsin-sensitive mitochondrial antigen that was named M2 antigen, in contrast to M1, the target of anti-cardiolipin antibody
    • the M2 antigen was located at the inner surface of the inner mitochondrial membrane of all mitochondria tested
      • the target antigens of M2 were identified in the 1980s as components of the 2-oxo-acid dehydrogenase complexes (2-OADC), the predominant target being the E2 subunit of pyruvate dehydrogenase complex, as judged by molecular cloning
      • PBC-specific AMA were later shown to recognise other enzymes of the 2-OADC, including the E2 subunits of branched chain oxoacid dehydrogenase complex (BCOADC), the oxoglutarate dehydrogenase complex (OGDC) and the PDC-E3 binding protein
  • patients with AMA and normal biochemical tests are at risk of developing true PBC (2)
  • specific autoantibodies to M2 autoantigen may be found in a minority of autoimmune hepatititis (AIH) (1,2,3)
  • AMA are the serum hallmark for PBC and this antibody at titres above 1:40 is highly specificity for PBC (2) and can be observed long before the disease is clinically overt
  • other conditions where AMAs may be present (1) include:
    • AMA are present (expectedly) in patients with AIH/PBC overlap syndrome, and also in chronic hepatitis C virus infected patients, and were described in patients with acute liver failure
      • AMA occur also in various rheumatological disorders which may co-exist with PBC notably Sjögren’s syndrome and systemic sclerosis and are described in non-liver related conditions with asymptomatic recurrent bacteriuria in women, pulmonary tuberculosis and leprosy


  • clinical associations of the subtypes of mitochondrial antibodies include:

    • M1 syphilis
    • M2 primary biliary cirrhosis & pseudosyphilis
    • M3 primary biliary cirrhosis
    • M5 undefined collagen disease
    • M6 isoniazid induced hepatitis


Last reviewed 08/2019