Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance.

The nine different antimitochondrial antibody specificities found in non-hepatic and hepatic disorders are described. Anti-M1 and anti-M7 antibodies are associated with infectious disorders such as syphilis or myocarditis. Anti-M3 and anti-M6 have been found in the course of a drug allergic disease due to Venocuran and iproniazid, and anti-M5 antibodies seem to occur occasionally in some forms of ANA-positive and ANA-negative collagen disorders. The M1- and M7-antigens are biochemically defined as cardiolipin and sarcosine dehydrogenase, respectively. Anti-M2, anti-M4, anti-M8, anti-M9 are associated with primary biliary cirrhosis (PBC). M2 was identified as alpha-ketoacid-dehydrogenase complex of the inner mitochondrial membrane, anti-M4 as sulfite oxidase, an enzyme of the mitochondrial intermembrane space, and anti-M9 as glycogen phosphorylase, a cytoplasmic enzyme. M8 copurifies with outer mitochondrial membranes derived from pig kidney. Anti-M9 can occur in the absence of anti-M2 while anti-M4 and anti-M8 are always associated with anti-M2. A progressive course of PBC can be predicted with high probability even at early stages of the disease when complement fixing antibodies against M2, M4 and/or M8 are present in patients' sera. In contrast, the presence of anti-M2/M9 antibodies heralds a benign course. The etiopathogenesis of PBC is still unknown. In PBC contact persons a strong stimulation of naturally occurring mitochondrial antibodies (NOMA) has been observed which was in contrast to the lack of this antibody type in PBC patients. Considering the generally accepted role of those antibodies in protecting individuals from infections, the failure of NOMA production may be a predisposing factor to acquire PBC more easily.