Anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)-glycoprotein 1 and oxidized low-density lipoprotein.
Anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)-glycoprotein 1 and oxidized low-density lipoprotein.
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抗磷脂抗体综合征患者的抗心磷脂抗体可识别 β(2)-糖蛋白 1 和氧化低密度脂蛋白中的表位。
DOI：
10.1161/01.cir.103.7.941
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发表时间：
2001
期刊：
影响因子：
37.8
通讯作者：
Witztum,JL
中科院分区：
文献类型：
--
作者：
Hörkkö,S;Olee,T;Mo,L;Branch,DW;WoodsJr,VL;Palinski,W;Chen,PP;Witztum,JL
背景-我们最近发现许多抗心磷脂抗体仅与氧化型心磷脂（OxCL）和/或OxCL-β2-糖蛋白1（β 2GP 1）加合物结合，而不与不能氧化的“还原型”心磷脂结合。为了验证这一假设，我们研究了24个血清，4个蛋白A纯化的IgG组分，和3个人单克隆抗体，都是从抗磷脂抗体综合征（APS）患者中分离出来的;测试还进行了7个对照。方法和结果：采用荧光免疫分析法，所有APS血清样品均与OxCL结合，而不与还原型CL结合，OxCL对结合的抑制率>95%，还原型CL对结合的抑制率不高。所有纯化的IgG组分均与β 2 GP 1结合，但仅当β 2 GP 1接种在用OxCL包被的微量滴定威尔斯孔上时。所有3种单克隆抗体仅与OxCL结合。在Western印迹上，IS 4和LJB 8与β 2GP 1以及氧化LDL的脱脂apoB结合，但不与天然apoB结合。Western blot显示IS 3与氧化型apoB结合。用CL氧化产物共价修饰β 2GP 1使其对APS血清样品、纯化IgG组分和单克隆抗体更具抗原性。结论-这些数据支持以下假设，即许多抗心磷脂抗体的表位需要CL氧化，其中一些表位是OxCL与β 2GP 1或apoB的共价加合物。
Background—We recently suggested that many anticardiolipin antibodies bind only to oxidized cardiolipin (OxCL) and/or to OxCL–β2-glycoprotein 1 (β2GP1) adducts but not to a “reduced” cardiolipin that is unable to undergo oxidation. To test this hypothesis, we investigated 24 sera, 4 protein A–purified IgG fractions, and 3 human monoclonal antibodies that were all isolated from patients with antiphospholipid antibody syndrome (APS); testing was also performed in 7 controls. Two monoclonal antibodies (IS3 and IS4) were selected for binding to CL and one was selected for binding to β2GP1 (LJB8).Methods and Results—By chemiluminescent immunoassay, all APS sera samples bound only to OxCL and not to reduced CL, and the binding was inhibited >95% by OxCL but not reduced CL. All purified IgG fractions bound to β2GP1 but only when the β2GP1 was plated on microtiter wells coated with OxCL. All 3 monoclonal antibodies bound only to OxCL. On Western blots, IS4 and LJB8 bound to β2GP1 as well as to delipidated apoB of oxidized LDL but not to native apoB. IS3 also bound to oxidized apoB on Western blot. Covalent modification of β2GP1 with oxidation products of CL made it more antigenic for APS serum samples, for purified IgG fractions, and for the monoclonal antibodies.Conclusions—These data support the hypothesis that oxidation of CL is needed to generate epitopes for many anticardiolipin antibodies and that some of these epitopes are covalent adducts of OxCL with β2GP1 or apoB.