Anti-mitochondrial antibodies (AMA) are

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

, consisting of

immunoglobulins An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

formed against

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

, primarily the mitochondria in

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

of the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

. The presence of AMA in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

or serum of a person may be indicative of the presence of, or the potential to develop, the

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

primary biliary cirrhosis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build ...

(PBC; also known as

primary biliary cholangitis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build ...

). 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. AMA ANTIBODIES

Antigens

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 Cardiolipin (IUPAC name 1,3-bis(''sn''-3’-phosphatidyl)-''sn''-glycerol) is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most ...

(

Anti-cardiolipin antibodies Anti-cardiolipin antibodies (ACA) are antibodies often directed against cardiolipin and found in several diseases, including syphilis, antiphospholipid syndrome, livedoid vasculitis, vertebrobasilar insufficiency, Behçet's syndrome, idiopathic s ...

, ACA) *M2 –

branched-chain alpha-keto acid dehydrogenase complex The branched-chain α-ketoacid dehydrogenase complex (BCKDC or BCKDH complex) is a multi-subunit complex of enzymes that is found on the mitochondrial inner membrane. This enzyme complex catalyzes the oxidative decarboxylation of branched, short-ch ...

*M3 –

outer mitochondrial membrane A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used t ...

*M4 –

sulfite oxidase Sulfite oxidase () is an enzyme in the mitochondria of all eukaryotes, with exception of the yeasts. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation ...

*M5 –

*M6 –

*M7 –

sarcosine dehydrogenase In enzymology, sarcosine dehydrogenase () is a mitochondrial enzyme that catalyzes the chemical reaction N-demethylation of sarcosine to give glycine. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH g ...

*M8 –

*M9 –

glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphory ...

Disease associations

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 cholangitis; M2 – autoimmune hepatitis; M1 –

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...

; M3 – drug-induced lupus erythematosus; M6 – drug-induced

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

; M7 –

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...

myocarditis Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...

; M5 –

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

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 Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two m ...

, asymptomatic recurrent

bacteriuria Bacteriuria is the presence of bacteria in urine. Bacteriuria accompanied by symptoms is a urinary tract infection while that without is known as asymptomatic bacteriuria. Diagnosis is by urinalysis or urine culture. ''Escherichia coli'' is the ...

in women, pulmonary

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

, and

leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...

are another type of AMA, and

is found on the

inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...

Development

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 Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...

AMA are found against all major liver antigens. *

Pyruvate dehydrogenase Pyruvate dehydrogenase is an enzyme that catalyzes the reaction of pyruvate and a lipoamide to give the acetylated dihydrolipoamide and carbon dioxide. The conversion requires the coenzyme thiamine pyrophosphate. Pyruvate dehydrogenase is us ...

, E2 subunits * 2-Oxo-glutarate dehydrogenase * Branched-chain 2-oxo-acid dehydrogenase Around 40.5% of acute liver failure patients were found to have elevated AMA, although a larger proportion (56.9%) had

anti-transglutaminase antibodies Anti-transglutaminase antibodies (ATA) are autoantibodies against the transglutaminase protein. Antibodies serve an important role in the immune system by detecting cells and substances that the rest of the immune system then eliminates. These cel ...

, usually associated with

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

References

{{Autoantibodies M M

Antigens

Disease associations

Development

See also

References