Highly sensitive and specific marker of Primary Biliary Cirrhosis. Also found in a small percentage of patients with autoimmune chronic active hepatitis. Autoantibodies often precede symptoms or markedly abnormal LFTs by many years. Primary biliary cirrhosis (PBC) is a multisystemic disease which is usually detected by abnormal liver function. Over 95% of patients with PBC have circulating anti-mitochondrial antibodies (AMA). Antimitochondrial antibodies of different specificity are also associated with other autoimmune liver disease. There are a number of antibody specificities which have been reported. These have been termed M1-M9. The most common and most useful are those with M2 specificity which are most frequently associated with primary biliary cirrhosis. The autoantibodies are IgG (predominantly IgG3) and IgM. Non-M2 antimitochondrial antibodies are frequently associated with other liver disease besides primary biliary cirrhosis. Anti-M1 antibodies recognise cardiolipin, anti- M2, M4, M8 and M9 are associated with PBC. The significance of antibodies recognising M8 and M9 is not yet fully understood. Anti-M4 antibodies are possibly associated with the ‘PBC-chronic active hepatitis overlap’ syndrome. M2 antibodies assocated with PBC. recognise mainly four closely related enzymes in the 2-oxoacid dehydrogenase complex; pyruvate dehydrogenase, branched chain α-ketoacid dehydrogenase, α-ketoglutarate dehydrogenase and an unknown protein. Most antibodies recognise the 74kDa (613 amino acid) acyltransferase E2 component of the enzymes (80-95%) often together with the related 52kDa protein (30-50% of sera). These proteins are the dihydrolipoamide acetyl transferase component. Less than 10% of sera react with neither or with the 39kDa component, the function of which is not known.

Highly sensitive and specific marker of Primary Biliary Cirrhosis, less commonly found in other autoimmune liver diseases.

Part of autoantibodies screen – gastric parietal cell and smooth muscle antibodies will also be done. Anti-mitochondrial antibodies of the M2 type are present in 90% of patients with PBC. Detection of AMA is, therefore, an extremely valuable diagnostic test; absence of AMA virtually excludes the diagnosis of PBC. Not all patients with proven PBC are symptomatic and anti-mitochondrial antibodies can be positive during this asymptomatic phase, which can last up to 20 years. AMA can also be found in a minority of patients with chronic active hepatitis or cirrhosis of unknown aetiology. AMA are also found, with very much lower frequency and at low levels, in other diseases and in apparently healthy individuals.

They are frequently associated with PBC in the presence of another autoimmune disease such as 2o Sjögrens disease, autoimmune thyroid disease, SLE or polymyositis. Can be associated with anti-smooth muscle antibodies in PBC/CAH overlap.

Serum Separator Tube (SST)

Indirect immunfluorescence mouse tissue (liver kidney stomach).

None

Negative/positive

5 – 7 days (screen); 10-14 days immunoblot

Immunology, The James Cook University Hospital