The immunology of atherothrombosis in the antiphospholipid syndrome: Antigen presentation and lipid intracellular accumulation

The immunology of atherothrombosis in the antiphospholipid syndrome: Antigen presentation and lipid intracellular accumulation
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DOI:
10.1016/j.autrev.2008.12.018
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发表时间:
2009-05-01
影响因子:
13.6
通讯作者:
Lopez, Luis R.
Lopez, Luis R.
中科院分区:
医学1区
文献类型:
--
作者:
Matsuura, Eiji;Kobayashi, Kazuko;Lopez, Luis R.

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抗磷脂综合征(APS)的特点是血清抗磷脂抗体(aPL)水平升高和血栓栓塞并发症,是获得性高凝状态的常见原因。血浆蛋白 β2-糖蛋白 I (β2GPI) 是 aPL 临床上最相关的抗原靶点。我们实验室最近的实验证据证实了这样的概念:含有氧化 LDL (oxLDL) 的 IgG 抗 β 2GPI 免疫复合物不仅促进了巨噬细胞中 oxLDL 的细胞内积累,而且还允许将 β 2GPI 表位呈递给致病性自身反应性 T 细胞。两种机制都需要 Fc gamma RI 介导的巨噬细胞/单核细胞的摄取。此外,多项临床研究表明,循环中 oxLDL/β 2GPI 复合物和针对这些复合物的 IgG 自身抗体的存在与自身免疫患者的血管炎症(即自身免疫介导的动脉粥样硬化血栓形成)显着相关。在本文中,我们回顾了有关 APS 患者自身免疫介导的动脉粥样硬化血栓形成的生化和免疫机制的最新发现。 (C) 2009 Elsevier B.V. 保留所有权利。
The antiphospholipid syndrome (APS), characterized by elevated serum levels of anti phospholipid antibodies (aPL) and thromboembolic complications, is a common cause of acquired hypercoagulability. The plasma protein beta 2-glycoprotein I (beta 2GPI) is the most clinically relevant antigenic target for aPL. Recent experimental evidence from our laboratory substantiated the concept that IgG anti-beta 2GPI immune complexes containing oxidized LDL (oxLDL) not only facilitated the intracellular accumulation of oxLDL in macrophages but also allowed the presentation of beta 2GPI epitopes to pathogenic autoreactive T cells. Both mechanisms required Fc gamma RI-mediated uptake by macrophages/monocytes. Furthermore, several clinical studies demonstrated that the presence of circulating oxLDL/beta 2GPI complexes and IgG autoantibodies to these complexes was significantly associated with vascular inflammation (i.e. autoimmune-mediated atherothrombosis) in autoimmune patients. In this article, we review recent findings concerning the biochemical and immunologic mechanisms involved in autoimmune-mediated atherothrombosis in patients with APS. (C) 2009 Elsevier B.V. All rights reserved.