M2-Antigen/M2-抗原

M2-Antigen
Diseases:
Primary Biliary Cirrhosis 

The M2 autoantigen is a major target of antimitochondrial autoantibodies (AMA), a characteristic serological feature in patients suffering from primary biliary cirrhosis (PBC). PBC is a severe autoimmune liver disease accompanied by destruction of intrahepatic bile ducts.

Molecular definition of the M2 antigen has shown it to be made up of at least 3 separate target proteins, the functionally similar so-called E2 subunits (or dihydrolipoamide transferases) of different mitochondrial dehydrogenase complexes:

• pyruvate dehydrogenase complex (PDC-E2; approx. 60 kDa)

• branched chain 2-oxo-acid dehydrogenase complex (BCOADC-E2; approx. 47 kDa)

• 2-oxoglutarate dehydrogenase complex (OGDC-E2; approx. 42 kDa).

Biochemically, these complexes catalyze the oxidative decarboxylation of various alpha-keto-acid substrates and mechanistically employ a prosthetic lipoamide group; they are located in the mitochondrial matrix in association with the inner membrane.

The most common reactivity of AMA positive PBC sera is against PDC-E2. Whereas some patients have AMA that react with PDC-E2 alone (95%), most patients also show reactivity against OGDC-E2 (39-88%) and/or BCOADC-E2 (53-55%). In fact, patients can be found with reactivity only against OGDC-E2 and/or BCOADC-E2 and no PDC-E2 autoantibodies. These patients will be missed in assays based on natural source-derived, predominantly PDC-E2-containing M2 antigen preparations.

DIARECT produces full-length PDC-E2, BCOADC-E2 and OGDC-E2 antigens in the baculovirus / insect cell system. The M2 antigen product is an equal-mass mix of these 3 proteins. 

相关疾病：原发性胆汁肝硬化 原发性胆汁肝硬化（PBC）是一种慢性的炎症性自身免疫肝病，病理表现包括肝内胆管的阻塞，干扰胆汁的分泌，导致纤维化和肝硬化。临床特征包括疲劳、搔痒和黄疸。在90-95% 的PBC病人血清中可检测到抗线粒体的抗体（M2），它们和其他的一些核内以及核膜的抗原（Sp100，gp210），都是重要的标记物。除了特异性自身抗体，其他的两个主要检测方面包括相容性的肝脏组织学和胆汁阻塞模型肝功能测试也用于PBC诊断。  M2自身抗原是抗线粒体抗体（AMA）的主要靶标，而AMA是原发性胆汁肝硬化（PBC）的血清学特征。PBC是一种严重的自身免疫干疾病伴随肝内胆道的损伤。M2抗原的分子定义显示其由三个独立的靶蛋白组成，功能类似于不同线粒体脱氢酶复合物的E2亚基（或二氢硫辛酰胺转移酶）：丙酮酸脱氢酶复合物（PDC-E2，约60kDa）侧链二氧酸脱氢酶复合体E2(BCOADC-E2，约47kDa)-氧戊二酸脱氢酶复合体E2 (OGDC-E2。约42kDa)从生化方面来讲，这些复合物催化不同的α-酮酸亚基氧化脱羧，2-氧(代)异戊酸脱氢酶(硫辛酰胺)AMA阳性PBC血清最常见的反应性是抗PDC-E2。然而一些有AMA的病人与PDC-E2单独的反应性为95%，大部分病人还有抗OGDC-E2（39-88%）及或BCOADC-E2（53-55%）的反应性。事实上，病人中可以发现抗OGDC-E2和/或BCOADC-E2的反应性，但没有PDC-E2的自身抗体，病人若是用天然来源的M2抗原检测，由于其中主要为PDC-E2，那么这些病人就会被漏检。

DIARECT生产的全长PDC-E2，BCOADC-E2，OGDC-E2抗原是在杆状病毒/昆虫细胞表达系统中表达的。