Anti-mitochondrial antibodies (AMA) are autoantibodies
, consisting of immunoglobulins
formed against mitochondria
, primarily the mitochondria in cells
of the liver
The presence of AMA in the blood
of a person may be indicative of the presence of, or the potential to develop, the autoimmune disease primary biliary cirrhosis
(PBC; also known as primary biliary cholangitis
). PBC causes scarring of liver tissue, confined primarily to the bile duct drainage system. AMA is present in about 95% of cases.
PBC is seen primarily in middle-aged women, and in those afflicted with other autoimmune diseases.
Several of the antigens associated with anti-mitochondrial antibodies have been identified.
[Berg PA, Klein R (1992) Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance: Dig Dis 10(2):85-101]
*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 these specific antigens have been associated with a number of conditions:
[Berg PA, Klein R (1986) Mitochondrial antigens and autoantibodies: from anti-M1 to anti-M9. Klin Wochenschr 64(19):897-909]
anti M2, M4, M8, and M9 are associated with primary biliary cirrhosis; M2 – autoimmune hepatitis; M1 – syphilis
; M3 – drug-induced lupus erythematosus; M6 – drug-induced hepatitis
; M7 – cardiomyopathy
; M5 – systemic lupus erythematosus
and undifferentiated collagenosis, autoimmune haemolytic anaemia.
[Labro MT, Andrieu MC, Weber M, Homberg JC (1976) A new pattern of non-organ- and non-species-specific anti-organelle antibody detected by immunofluorescence: the mitochondrial antibody number 5. Clin Exp Immunol 31(3):357-366]
These associations are not completely specific and should not be relied upon solely for diagnosis.
Antimitochondrial antibodies can also be detected in Sjögren's syndrome
, systemic sclerosis
, asymptomatic recurrent bacteriuria
in women, pulmonary tuberculosis
, and leprosy
Anti-cardiolipin antibodies are another type of AMA, and cardiolipin is found on the inner mitochondrial membrane.
A cause of AMA has been postulated to be 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
Around 40% of acute liver failure patients were found to have elevated AMA, although a larger proportion (57%) had anti-transglutaminase antibodies, usually associated with coeliac disease.