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Characterization of the binding domains on platelet glycoproteins Ib-IX and
IIb/IIIa complexes for the quinine/quinidine-dependent antibodies
BH Chong, XP Du, MC Berndt, S Horn and CN Chesterman
Department of Haematology, Prince of Wales Hospital, School of Pathology,
University of New South Wales, Randwick, Australia.
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.
Volume 77,
Issue 10,
pp. 2190-2199,
05/15/1991
Copyright © 1991 by The American Society of Hematology
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