抗ミトコンドリア抗体

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any of a large variety of proteins normally present in the body or produced in response to an antigen which it neutralizes, thus producing an immune response

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抗体,免疫体,抗毒素

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/26 18:24:46」(JST)

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Anti-mitochondrial antibodies (AMA) are autoantibodies, consisting of immunoglobulins formed against mitochondria,^[1] primarily the 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.^[2]

Immunofluorescence staining pattern of AMA shown on stomach (top left), liver (top right), kidney (bottom left) and hep-20-10 cells (bottom right).

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.^[3]

Pyruvate dehydrogenase, E2 subunits
2-Oxo-glutarate dehydrogenase
Branched-chain 2-oxo-acid dehydrogenase

Anti-cardiolipin antibodies are another type of AMA,and cardiolipin is found on the inner mitochondrial membrane.

Antigens

Several of the antigens associated with these antibodies have been identified.^[4]

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:^[5] 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.^[6]

These associations are not completely specific and should not be relied upon solely for diagnosis.

Antimitochondrial antibodies can also be found in Sjögren’s syndrome, systemic sclerosis, asymptomatic recurrent bacteriuria in women, pulmonary tuberculosis, and leprosy.

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).^[3] 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.^[7]^[8]

References

^ MedlinePlus Encyclopedia 003529
^ Oertelt S, Rieger R, Selmi C, Invernizzi P, Ansari A, Coppel R, Podda M, Leung P, Gershwin M (2007). "A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis". Hepatology 45 (3): 659–65. doi:10.1002/hep.21583. PMID 17326160.
^ ^a ^b Leung PS, Rossaro L, Davis PA, et al. (2007). "Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis". Hepatology (Baltimore, Md.) 46 (5): 1436–42. doi:10.1002/hep.21828. PMC 3731127. PMID 17657817.
^ Berg PA, Klein R (1992) Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance. Dig Dis 10(2):85-101
^ Berg PA, Klein R (1986) Mitochondrial antigens and autoantibodies: from anti-M1 to anti-M9. Klin Wochenschr 64(19):897-909
^ 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
^ Nickowitz RE, Worman HJ (1993). "Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210". J. Exp. Med. 178 (6): 2237–42. doi:10.1084/jem.178.6.2237. PMC 2191303. PMID 7504063.
^ Bauer A, Habior A (2007). "Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosis". J. Clin. Lab. Anal. 21 (4): 227–31. doi:10.1002/jcla.20170. PMID 17621358.

UpToDate Contents

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1. 原発性胆汁性肝硬変の病因 pathogenesis of primary biliary cirrhosis
2. 原発性胆汁性肝硬変の臨床症状、診断、および自然経過 clinical manifestations diagnosis and natural history of primary biliary cirrhosis
3. 自己免疫性肝炎の血清学的マーカー serologic markers of autoimmune hepatitis
4. 自己免疫性肝炎の亜型の定義および治療 definition and treatment of variants of autoimmune hepatitis
5. 全身性硬化症（強皮症）の消化器症状 gastrointestinal manifestations of systemic sclerosis scleroderma

English Journal

Long-term outcomes in antimitochondrial antibody negative primary biliary cirrhosis.

Juliusson G1, Imam M2, Björnsson ES1,3, Talwalkar JA2, Lindor KD4.
Scandinavian journal of gastroenterology.Scand J Gastroenterol.2016 Jun;51(6):745-52. doi: 10.3109/00365521.2015.1132337. Epub 2016 Jan 18.
Objectives Antimitochondrial antibodies (AMA) are a sensitive and specific marker for primary biliary cirrhosis (PBC). AMAs are present in 95% of patients with PBC. However, 5% do not have AMAs and data on these patients is scarce. We aim to evaluate the long-term outcomes of patients with AMA negat
PMID 26776319

A contemporary perspective on the molecular characteristics of mitochondrial autoantigens and diagnosis in primary biliary cholangitis.

Leung PS1, Choi J1, Yang G1, Woo E1, Kenny TP1, Gershwin ME1.
Expert review of molecular diagnostics.Expert Rev Mol Diagn.2016 Mar 30:1-9. [Epub ahead of print]
Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disease characterized by immune mediated destruction of the intrahepatic small bile ducts and the presence of antimitochondrial antibodies (AMAs). The mitochondrial autoantigens have been identified as the E2 subunits of the 2-oxo-acid
PMID 26953925

Red Blood Cell Distribution Width to Platelet Ratio is Related to Histologic Severity of Primary Biliary Cirrhosis.

Wang H1, Xu H, Wang X, Wu R, Gao X, Jin Q, Niu J.
Medicine.Medicine (Baltimore).2016 Mar;95(11):e3114. doi: 10.1097/MD.0000000000003114.
We aimed to investigate whether red blood cell distribution width (RDW) and RDW to platelet ratio (RPR) were related to the histologic severity of primary biliary cirrhosis (PBC).Seventy-three treatment-naïve PBC patients who had undergone a liver biopsy between January 2010 and January 2015 were e
PMID 26986159

Japanese Journal

Autoantibodies by line immunoassay in patients with primary biliary cirrhosis

Saito Hironobu,Takahashi Atsushi,Abe Kazumichi,Okai Ken,Katsushima Fumiko,Monoe Kyoko,Kanno Yukiko,Ohira Hiromasa
Fukushima Journal of Medical Science 58(2), 107-116, 2012
… Objectives: We attempted to measure multiple autoantibodies simultaneously using line immunoassay (LIA) in patients with primary biliary cirrhosis (PBC) with or without anti-mitochondrial antibody (AMA) and patients with PBC-autoimmune hepatitis (AIH) overlap, and we examined the clinical significance of measuring these autoantibodies. … Nine antibodies (AMA-M2, M2-3E, Sp100, PML, gp210, Ro-52, LKM-1, LC-1 and SLA/LP) were detected by LIA, and AMA-M2 and anti-centromere antibody (ACA) were detected by ELISA. …
NAID 130002566783

原発性胆汁性肝硬変に全身性エリテマトーデスを合併した2例

斎藤広信,高橋敦史,阿部和道 [他],物江恭子,菅野有紀子,横川順子,大平弘正
肝臓 52(3), 169-175, 2011-03-25
症例1は65歳，女性．19年前，蝶形紅斑と光線過敏があり，抗核抗体陽性，抗DNA抗体陽性を認め，SLEと診断された．プレドニゾロン（PSL）内服にて症状は改善し，PSL 10 mg/日の隔日投与でSLEの活動性はなく経過していた．SLE診断時から肝機能異常があり，精査目的に当科へ紹介となった．胆道系酵素優位の肝障害，抗ミトコンドリア抗体（AMA）陽性，肝生検にてPBC（Scheuer分類のII期） …
NAID 10029285191