Reactivity of autoantibodies from chronic ITP patients with recombinant glycoprotein IIIa peptides.
Reactivity of autoantibodies from chronic ITP patients with recombinant glycoprotein IIIa peptides.
复制标题
慢性 ITP 患者的自身抗体与重组糖蛋白 IIIa 肽的反应性。
DOI：
10.1111/j.1365-2141.1995.tb05266.x
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发表时间：
1995
影响因子：
6.5
通讯作者：
McMillan,R
中科院分区：
文献类型：
--
作者：
Bowditch,RD;Tani,P;McMillan,R
慢性免疫性血小板减少症是一种自身免疫性疾病，其特征在于由于形成针对血小板相关抗原的自身抗体而导致的破坏性血小板减少症。大多数抗血小板自身抗体与血小板糖蛋白IIb/IIIa或Ib/IX复合物反应，而一些血浆自身抗体与糖蛋白IIIa反应。我们实验室以前的研究表明，大多数血小板GPIIb/IIIa相关自身抗体与完整复合物结合，与EDTA解离复合物结合的亲和力要低得多，表明表位是复合物依赖性的。为了进一步评估这一点，我们研究了血小板相关自身抗体和血浆自身抗体和同种抗体洗脱液与大的重组GPIIIa肽的结合：肽1（GPIIIa Gly 1-Val 200）;肽2（GPIIIa Arg 150-Glu 400）;肽3（GPIIIa Lys 350-Asp 550）;肽4（GPIIIa Asn 450-Val 700）和肽5（GPIIIa Trp 715-Thr 762，胞质片段）。在检测的33种血小板相关抗体洗脱液中，所有洗脱液均与GPIIb/IIIa复合物强烈结合，但只有一种洗脱液显示与一种固定化肽（肽3）显著结合（高于对照值>3 SD）。相反，已知与GPIIIa特定区域结合的抗体（鼠单克隆抗体，抗LIBS 2;抗GPIIIa胞质片段的血浆自身抗体和抗P1 A1抗体）均与含有适当表位的GPIIIa肽强烈结合。基于这些和我们以前的结果，我们得出结论，慢性ITP患者的血小板相关抗体很少与GPIIIa单独定位的表位结合。
Chronic immune thrombocytopenia is an autoimmune disorder characterized by destructive thrombocytopenia due to the formation of autoantibodies against platelet‐associated antigens. Most antiplatelet autoantibodies react with either the platelet glycoprotein IIb/IIIa or Ib/IX complex, whereas some plasma autoantibodies react with glycoprotein IIIa. Previous studies from our laboratory suggested that most platelet‐associated autoantibodies to platelet GPIIb/IIIa, which bind to the intact complex, bind much less avidly to the EDTA‐dissociated complex, suggesting that the epitopes were complex‐dependent. To evaluate this further we have studied the binding of platelet‐associated autoantibody and plasma auto‐ and alloantibody eluates to large recombinant GPIIIa peptides: peptide 1 (GPIIIa Gly1‐Val200); peptide 2 (GPIIIa Arg150‐Glu400); peptide 3 (GPIIIa Lys350‐Asp550); peptide 4 (GPIIIa Asn450‐Val700) and peptide 5 (GPIIIa Trp715‐Thr762, cytoplasmic fragment). Of the 33 platelet‐associated antibody eluates tested, all bound avidly to the GPIIb/IIIa complex, but only one showed significant binding (>3 SD above control values) to one of the immobilized peptides (peptide 3). Conversely, antibodies known to bind to specific regions of GPIIIa (murine monoclonal antibody, anti‐LIBS2; plasma autoantibody against the GPIIIa cytoplasmic fragment and anti‐P1A1antibody) all bound avidly to the GPIIIa peptide containing the appropriate epitope. Based on these and our previous results, we conclude that platelet‐associated antibodies from chronic ITP patients rarely bind to epitopes localized to GPIIIa alone.