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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2002-07-2175. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2175v1 102/5/1670    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Asvadi, P. Articles by Chong, B. H. Search for Related Content PubMed PubMed Citation Articles by Asvadi, P. Articles by Chong, B. H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2003, Vol. 102, No. 5, pp. 1670-1677 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Drug-induced thrombocytopenia: localization of the binding site of GPIX-specific quinine-dependent antibodies Parisa Asvadi, Zohra Ahmadi, and Beng H. Chong From the Centre for Thrombosis and Vascular Research, Department of Medicine, St George Clinical School, Kogarah, Australia, The University of New South Wales, Sydney, Australia, and National Heart Center, Singapore. Immune thrombocytopenia is a common complication of therapy with a large number of drugs. The most widely studied drug-induced immune thrombocytopenia (DIT) is caused by quinine. In most cases of DIT, antibodies bind to the platelet membrane glycoprotein (GP) Ib-IX complex in a drug-dependent fashion and bring about increased platelet clearance by the reticuloendothelial system resulting in thrombocytopenia. Here, we report the characterization of the quinine-dependent antibody activity of sera from 13 patients with quinine-induced thrombocytopenia. In our series of patients, GPIX was the most prevalent target of quinine-dependent antibodies. To identify the structural determinants of GPIX recognized by quinine-dependent antibodies, 4 chimeric mouse/human GPIX constructs and stable Chinese hamster ovary (CHO) cell lines that expressed the chimeras in association with GPIb and GPIb were produced. The analysis of 6 patient sera with the chimeric cell lines provided evidence for localization of the anti-GPIX quinine-dependent antibody binding site to the C-ext region (amino acid [aa] 64-135) of human GPIX. Further characterization of the C-ext region of the GPIX indicated that replacement of the Arg110 and Gln115 of the human GPIX with the corresponding residues from mouse (Gln and Glu, respectively) resulted in a significant reduction in the binding of GPIX antibodies in our series of patients, with Arg110Gln, giving a more pronounced effect than Gln115Glu. Hence, these 2 residues, particularly Arg110, play an important role in the structure of the antigenic site on GPIX recognized by anti-GPIX antibodies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Peterson, T. N. Nelson, A. J. Kanack, and R. H. Aster Fine specificity of drug-dependent antibodies reactive with a restricted domain of platelet GPIIIA Blood, February 1, 2008; 111(3): 1234 - 1239. [Abstract] [Full Text] [PDF] R. H. Aster and D. W. Bougie Drug-Induced Immune Thrombocytopenia N. Engl. J. Med., August 9, 2007; 357(6): 580 - 587. [Full Text] [PDF]

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