title: Characterization of the binding domains on platelet glycoproteins Ib-IX and IIb/IIIa complexes for the quinine/quinidine-dependent antibodies.
abstract: 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.
authors.affiliation: Department of Haematology, Prince of Wales Hospital, School of Pathology, University of New South Wales, Randwick, Australia.
authors.forename: B H
authors.initials: BH
authors.lastname: Chong
authors.forename: X P
authors.initials: XP
authors.lastname: Du
authors.forename: M C
authors.initials: MC
authors.lastname: Berndt
authors.forename: S
authors.initials: S
authors.lastname: Horn
authors.forename: C N
authors.initials: CN
authors.lastname: Chesterman
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D001665:Binding Sites; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007536:Isomerism; D010980:Platelet Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D011233:Precipitin Tests; D011803:Quinine / Q000009:adverse effects / Q000276:immunology*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000276:immunology*
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins; D011803:Quinine