Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Curr Mol Med. 2011 Dec;11(9):719-25. doi: 10.2174/156652411798062377.
Beta2-glycoprotein I (β2-GPI), an abundant 50 kDa plasma glycoprotein, is the most common target for antiphospholipid antibodies (aPLs). These autoantibodies are associated with thrombotic events in patients with anti-phospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE) and are proatherogenic. β2-GPI can also stimulate a vigorous adaptive cellular immune response in these patients. Although much is known about β2-GPI as a cofactor in autoimmune diseases, crucial information is still lacking to clarify why this abundant self plasma protein is the target of autoimmune responses. Throughout the years, a remarkable number of theories have been proposed to explain how the immune system recognises self. On the basis of a large variety of epidemiological, clinical and experimental evidence, it has been suggested that an unfortunate interplay of genetic susceptibility and environmental factors may play an important role in generating an abnormal immune response. Among the environmental factors, oxidative stress is one of the major events causing protein structural modifications, thus inducing the appearance of neo/cryptic epitopes of β2-GPI able to activate the immune system. In particular, oxidized β2-GPI is able to induce phenotypic and functional maturation of dendritic cells which represent the link between innate and adaptive immunity. Chronic activation of autoimmune reactions against this self protein modified by oxidative events may contribute to local and systemic inflammation, thus sustaining endothelial dysfunction in patients with APS, SLE and cardiovascular diseases. The role of oxidative stress in β2-GPI-mediated immune response is described in the light of our research experience and of relevant literature emerging in the field.
β2-糖蛋白 I（β2-GPI），一种丰富的 50kDa 血浆糖蛋白，是抗磷脂抗体（aPL）最常见的靶标。这些自身抗体与抗磷脂抗体综合征（APS）和系统性红斑狼疮（SLE）患者的血栓事件有关，并且具有促动脉粥样硬化作用。β2-GPI 还可以刺激这些患者产生强烈的适应性细胞免疫反应。尽管人们对β2-GPI 作为自身免疫性疾病的辅助因子有了很多了解，但仍缺乏关键信息来阐明为什么这种丰富的自身血浆蛋白是自身免疫反应的靶标。多年来，提出了许多理论来解释免疫系统如何识别自身。基于大量的流行病学、临床和实验证据，有人提出，遗传易感性和环境因素的不幸相互作用可能在产生异常免疫反应中发挥重要作用。在环境因素中，氧化应激是导致蛋白质结构修饰的主要事件之一，从而诱导β2-GPI 出现新的/隐匿表位，能够激活免疫系统。特别是，氧化的β2-GPI 能够诱导树突状细胞的表型和功能成熟，树突状细胞是先天免疫和适应性免疫之间的联系。针对这种由氧化事件修饰的自身蛋白的自身免疫反应的慢性激活可能导致局部和全身炎症，从而维持 APS、SLE 和心血管疾病患者的内皮功能障碍。本文将根据我们的研究经验和该领域的相关文献，阐述氧化应激在β2-GPI 介导的免疫反应中的作用。
