Anti- M2

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). Detection of AMA’s are, therefore, an extremely valuable diagnostics 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 the 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.

Anti-mitochondrial antibodies have been shown to have a number of different specificities. Several antigens, termed M1-M9, have been recognised from tissue distribution and chemical properties. M2, M4, M8 and M9 are associated with PBC and , of these, M2 are the most characteristic. The significance of antibodies recognising M8 and M9 is not yet fully understood, however, M9 antibodies may be associated with a more benign course of the disease. Anti-M4 antibodies are frequently associated with ‘PBC-chronic active hepatitis overlap’ syndrome.

The antigens recognised by anti-mitochondrial M2 antibodies are trypsin sensitive proteins which are four closely related enzymes in the 2-oxoacid dehydrogenase complex. Pyruvate dehydrogenase, branched chain alpha-ketoacid dehydrogenase, alpha-ketoglutarate dehydrogenase and an unknown protein.

AMA have been traditionally detected by indirect immunofluorscence on sections of animal kidney or cell lines such as Hep2. In recent years, several reports have described the detection of AMA by ELISA using submitochondrial particles or partially purified antigen preparations.