Quinine-dependent antibodies bind a restricted set of epitopes on the glycoprotein Ib-IX complex: Characterization of the epitopes
Quinine-dependent antibodies bind a restricted set of epitopes on the glycoprotein Ib-IX complex: Characterization of the epitopes
复制标题
DOI：
10.1182/blood.v92.7.2366.2366_2366_2373
复制
发表时间：
1998-10-01
期刊：
影响因子：
20.3
通讯作者：
Chong, BH
中科院分区：
文献类型：
--
作者：
Burgess, JK;Lopez, JA;Chong, BH
严重的免疫性血小板减少症是奎宁治疗的特异质并发症。虽然在大多数情况下，负责的抗体是针对血小板膜糖蛋白（GP）的Ib-IX，GPIIb-IIIa或两个表位的特异性也有报道。本研究的目的是表征GPIb-IX特异性奎宁依赖性抗体的结合位点。使用流式细胞术、单克隆抗体特异性固定血小板抗原试验和差示吸附研究，检测抗体与稳定转染了编码该复合物的三种基因（Ib α、Ib β或IX）的各种组合的中国仓鼠卵巢细胞或小鼠L细胞的结合。在奎宁的存在下，从15例奎宁诱导的血小板减少症的细胞结合的血清中的IgG，表现出三种不同的模式。组1血清含有至少两个抗体群，一个结合GPIb α，另一个识别GPIX，组2血清含有药物依赖性结合GPIX的抗体，组3血清含有识别GPIb α上奎宁依赖性表位的抗体。因此，奎宁依赖性抗体分为两个独立结合GPIb α和GPIX的不同群体。使用在特定位点切割GPIb α的蛋白酶，我们已经证明GPIb α特异性抗体结合II-氨基酸（283至293）区域。肽抑制研究提供了该区域含有GPIb α特异性奎宁依赖性抗体表位的确证性证据。(C)1998年，美国血液学会。
Severe immune thrombocytopenia is an idiosyncratic complication of quinine therapy. Although in most cases the responsible antibody is directed against platelet membrane glycoprotein (GP) Ib-IX, specificity for GPIIb-IIIa or both epitopes has also been reported. The objective of this study was to characterize the binding site of GPIb-IX-speciiic quinine-dependent antibodies. Antibody binding to Chinese hamster ovary cells or mouse L cells stably transfected with various combinations of the three genes (Ib alpha, Ib beta, or IX) that encode this complex was detected using flow cytometry, monoclonal antibody-specific immobilization of platelet antigens assay, and differential adsorption studies. IgG in sera from 15 patients with quinine-induced thrombocytopenia binding to the cells, in the presence of quinine, showed three distinct patterns. Group 1 sera contained at least two antibody populations, one which binds to GPIb alpha and another which recognizes GPIX, Group 2 sera contained an antibody which binds drug dependently to GPIX, and Group 3 sera contained an antibody which recognizes a quinine-dependent epitope on GPIb alpha. Thus, the quinine-dependent antibodies fall into two distinct populations that bind to GPIb alpha and GPIX independently. Using proteases which cleave GPIb alpha at specific sites, we have shown that the GPIb alpha-specific antibody binds to an II-amino acid (283 to 293) region. Peptide inhibition studies provide confirmatory evidence that this region contains the epitope for the GPIb alpha-specific quinine-dependent antibody. (C) 1998 by The American Society of Hematology.