Chong B H, Du X P, Berndt M C, Horn S, Chesterman C N
Department of Haematology, Prince of Wales Hospital, School of Pathology, University of New South Wales, Randwick, Australia.
Blood. 1991 May 15;77(10):2190-9.
Sera of 12 patients with quinine/quinidine-induced thrombocytopenia showed drug-dependent antibody binding to glycoprotein (GP) Ib-IX complex. The reaction with GPIb-IX complex of 11 of these 12 sera was strongly inhibited by the complex-specific monoclonal antibodies (MoAbs) AK1 and SZ1. The exception was a quinine-induced serum designated BU. The reaction of the six quinidine-induced sera was also partially blocked by an anti-GPIX MoAb, FMC25. Only 3 of the 12 patient sera showed drug-dependent antibody binding to GPIIb/IIIa, which was strongly inhibited by the anti-GPIIIa MoAb 22C4, and the anti-GPIIb alpha MoAb SZ22. With detergent-solubilized Serratia metalloprotease-treated platelets, quinine/quinidine-induced sera, except BU, immunoprecipitated a membrane-bound proteolytic fragment of GPIb-IX complex. In contrast, BU immunoprecipitated glycocalicin and a 40-Kd peptide tail fragment of GPIb alpha from the cell supernatant. Using purified GPIb-IX complex or its components as the target antigen, all the quinine-induced sera, except BU, immunoprecipitated GPIb-IX complex but failed to immunoprecipitate GPIb, GPIX, or the complex reformed from GPIb and GPIX. The quinidine-induced sera strongly immunoprecipitated purified GPIb-IX complex, weakly immunoprecipitated purified GPIX and the recombined complex, but did not immunoprecipitate purified GPIb. The combined data suggest that one quinine-dependent antibody (BU) recognizes an epitope in the peptide tail region of GPIb alpha and the other five quinine-dependent antibodies react with a complex-specific epitope on the membrane-associated region of GPIb-IX complex, whereas each of the six quinidine-induced sera contain two drug-dependent antibodies, one reactive with the GPIb-IX complex-specific epitope and the other reactive with GPIX. The binding domain(s) on GPIIb/IIIa for the quinine/quinidine-dependent antibodies appear to be sterically close to the epitopes for 22C4 and SZ22.
12例奎宁/奎尼丁诱导的血小板减少症患者的血清显示药物依赖性抗体与糖蛋白（GP）Ib-IX复合物结合。这12份血清中的11份与GPIb-IX复合物的反应被复合物特异性单克隆抗体（MoAbs）AK1和SZ1强烈抑制。例外的是一份名为BU的奎宁诱导血清。6份奎尼丁诱导血清的反应也被抗GPIX MoAb FMC25部分阻断。12例患者血清中只有3份显示药物依赖性抗体与GPIIb/IIIa结合，该反应被抗GPIIIa MoAb 22C4和抗GPIIbα MoAb SZ22强烈抑制。用去污剂溶解的经粘质沙雷氏菌金属蛋白酶处理的血小板，除BU外，奎宁/奎尼丁诱导的血清免疫沉淀出GPIb-IX复合物的膜结合蛋白水解片段。相反，BU从细胞上清液中免疫沉淀出糖萼蛋白和GPIbα的40-Kd肽尾片段。以纯化的GPIb-IX复合物或其组分为靶抗原，除BU外，所有奎宁诱导的血清均免疫沉淀出GPIb-IX复合物，但未能免疫沉淀出GPIb、GPIX或由GPIb和GPIX重组的复合物。奎尼丁诱导的血清强烈免疫沉淀纯化的GPIb-IX复合物，弱免疫沉淀纯化的GPIX和重组复合物，但不免疫沉淀纯化的GPIb。综合数据表明，一种奎宁依赖性抗体（BU）识别GPIbα肽尾区域的一个表位，其他五种奎宁依赖性抗体与GPIb-IX复合物膜相关区域的复合物特异性表位反应，而6份奎尼丁诱导血清中的每一份都含有两种药物依赖性抗体，一种与GPIb-IX复合物特异性表位反应，另一种与GPIX反应。奎宁/奎尼丁依赖性抗体在GPIIb/IIIa上的结合域在空间上似乎与22C4和SZ22的表位接近。
