Anti-mitochondrial antibodies (AMA) are autoantibodies, consisting of immunoglobulins formed against mitochondria, primarily mitochondria in cells of the liver. The presence of AMAs in the blood or serum of a person is indicative of several autoimmune diseases such as primary biliary cirrhosis (PBC) (a scarring of liver tissue, confined primarily to the bile duct drainage system of the liver). It is present in about 95% of cases.
Primary biliary cirrhosis is seen primarily in middle-aged women, and in those afflicted with other autoimmune diseases. PBC is an autoimmune disorder, a condition in which the human body's immune defense system mistakenly attacks the body's own cells, or in this case parts of the cells.
Cause of AMAs is postulated that xenobiotic-induced and/or oxidative modification of mitochondrial autoantigens is a critical step leading to loss of tolerance. In acute liver failure AMA are found against all major liver antigens.
- Pyruvate dehydrogenase, E2 subunits
- 2-oxo-glutarate dehydrogenase
- Branched chain 2-oxo-acid dehydrogenase
Several of the antigens associated with these antibodies have been identified.
- M1 - cardiolipin
- M2 - branched-chain alpha-keto acid dehydrogenase complex
- M3 - outer mitochondrial membrane
- M4 - sulfite oxidase
- M5 - outer mitochondrial membrane
- M6 - outer mitochondrial membrane
- M7 - sarcosine dehydrogenase
- M8 - outer mitochondrial membrane
- M9 - glycogen phosphorylase
Antibodies to the antigens are associated with a number of conditions: anti M2, M4, M8 and M9 are associated with primary bilary cirrhosis; M2 - autoimmune hepatititis; M1 - syphilis; M3 - drug induced lupus erythematosus; M6 - drug induced hepatitis; M7 - cardiomyopathy, myocarditis; M5 - systemic lupus erythematosus and undifferentiated collagenosis, autoimmune haemolytic anaemia.
These associations are not completely specific and should not be relied upon solely for diagnosis.
Correlation with non-mitochondrial antigens
Fifty seven percent of acute liver failure patients had elevated anti-transglutaminase antibodies (anti-tTG), which correlate with gluten-sensitive enteropathy (see coeliac disease, gluten-sensitive enteropathy associated conditions). The inflammation produced by gluten-sensitive cellular immunity may cause the oxidative stress resulting in the modification of mitochondrial antigens and acute liver failure. Anti-gp210 antibodies are also found in 47% of PBC patients.