Are posttranslational modifications of β2-glycoprotein I markers for thrombotic risk? Are they triggers of autoimmunity?
Are posttranslational modifications of β2-glycoprotein I markers for thrombotic risk? Are they triggers of autoimmunity?
复制标题
β2-糖蛋白 I 标记物的翻译后修饰是否会导致血栓风险？
DOI：
10.1002/art.30382
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发表时间：
2011
影响因子：
--
通讯作者：
Salmon,JaneE
中科院分区：
文献类型：
--
作者：
Lockshin,MichaelD;Salmon,JaneE
30多年来，我们已经知道血栓形成和胎儿丢失是抗磷脂综合征（APS）的标志性特征。我们了解了这种综合征的主要功能成分：抗体，主要是IgG类，与自身抗原结合，在许多情况下是β2-糖蛋白I（β2-GPI），其本身与带负电荷的磷脂结合，或者更可能与细胞表面受体（如ApoER 2）结合。这些事件启动导致血栓形成的细胞内或细胞外信号链。1-5虽然化学和细胞生物学是熟悉的，它一直是不可能预测在谁和在什么时间点抗磷脂抗体的患者将有临床events.Multiple动物和人类的研究阐明导致临床APS的诊断的病理生理学要素。通过模型测试的假设集中于从抗体首次出现到血栓形成的特定事件，包括脆弱组织的表型变化、抗体触发的炎症和损伤途径、凝血蛋白和血小板的改变、通过刺激表面受体的细胞活化、环境损伤和共存的遗传血栓状态。
For over 30 years, we have known that thrombosis and fetal loss are the signature features of antiphospholipid syndrome (APS). We understand the major functional components of this syndrome: antibodies, primarily of IgG class, bind to an autoantigen, in many cases β2-glycoprotein I (β2-GPI), that itself binds to either negatively charged phospholipids or, more likely, to cell surface receptors such as ApoER2. These events initiate a chain of intracellular or extracellular signals that lead to thrombosis. 1–5 Although the chemistry and cell biology is familiar, it has not been possible to predict in whom and at what point in time patients with antiphospholipid antibodies will have clinical events.Multiple studies in animals and humans elucidate elements of the pathophysiology that lead to a diagnosis of clinical APS. The hypotheses tested by the models focus on specific events from the first appearance of antibody to thrombosis, including phenotypic changes in vulnerable tissue, antibody triggered pathways of inflammation and injury, alterations in coagulation proteins and platelets, cellular activation by stimulation of surface receptors, environmental insults, and coexistent genetic thrombotic states.