DRUG-ANTIBODY-PLATELET INTERACTION IN QUININE-INDUCED AND QUINIDINE-INDUCED THROMBOCYTOPENIA
DRUG-ANTIBODY-PLATELET INTERACTION IN QUININE-INDUCED AND QUINIDINE-INDUCED THROMBOCYTOPENIA
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DOI：
10.1172/jci110710
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发表时间：
1982-01-01
影响因子：
15.9
通讯作者：
ASTER, RH
中科院分区：
文献类型：
--
作者：
CHRISTIE, DJ;ASTER, RH
使用电免疫测定法测定血小板结合IgG，研究了奎宁和奎尼丁依赖抗体与血小板的结合。4例药物性血小板减少患者的抗体与血小板的相互作用有显著差异：在高药物浓度下与血小板结合的关联常数从0.29到2.6倍不等。107 M-1，抗体分子结合的最大数量为36,000-161,000/血小板，达到抗体与血小板结合的半最大数量所需的药物量为2-60 .mu。只有1种抗体与患者致敏的药物的立体异构体发生交叉反应。在药物：抗体的最高摩尔比10000:1时，抗体与血小板的结合得到增强，而不是像传统的半抗原依赖反应那样被抑制。药物-抗体-血小板反应不受VIII因子/血管性血友病蛋白、非特异性聚集IgG或热不稳定补体成分的影响。用3H奎宁预处理后，每个血小板保留了10万分子药物，但无法结合可检测到的抗体。同时使用奎宁依赖抗体和3H奎宁处理的血小板在反复洗涤后保留的药物明显多于使用药物和正常血清处理的血小板。显然，在奎宁和奎尼丁诱导的血小板减少症中，药物和抗体首先在可溶性相结合形成复合物，然后以高亲和力与血小板表面的受体结合（无辜旁观者反应）。这些抗体在促进它们与血小板结合所需的药物量、它们识别的血小板受体的数量和它们的结合亲和力方面是异质的。
Binding of quinine- and quinidine-dependent antibodies to platelets was studied using an electroimmunoassay to measure platelet-bound IgG. Antibodies from 4 patients with drug-induced thrombocytopenia differed significantly in their interaction with platelets: association constants for binding to platelets at high drug concentrations ranged from 0.29 to 2.6 .times. 107 M-1, the maximum number of antibody molecules bound was 36,000-161,000/platelet, the amount of drug necessary to achieve half-maximum binding of antibodies to platelets was 2-60 .mu.M and only 1 of the antibodies cross-reacted with the stereoisomer of the drug to which the patient was sensitized. Binding of the antibodies to platelets was enhanced at the highest achievable molar ratio of drug:antibody, 10,000:1, rather than being inhibited, as would be expected in a conventional, hapten-dependent reaction. The drug-antibody-platelet reaction was unaffected by Factor VIII/von Willebrand protein, nonspecifically aggregated IgG, or heat-labile complement components. After pretreatment with 3H quinine, platelets retained several 100,000 molecules of drug each, but failed to bind detectable amounts of antibody. Platelets treated simultaneously with quinine-dependent antibody and 3H quinine retained significantly more drug after repeated washes than platelets treated with drug and normal serum. Evidently in quinine- and quinidine-induced thrombocytopenia, drug and antibody combine first in the soluble phase to form a complex, which then binds with high affinity to a receptor on the platelet surface (innocent bystander reaction). These antibodies are heterogenous in respect to the amount of drug required to promote their binding to platelets, the number of platelet receptors they recognize and their binding affinities.