Characteristics of quinine- and quinidine-induced antibodies specific for platelet glycoproteins IIb and IIIa. Blood 1991 Jun 15;77(12):2668-76
Date
06/15/1991Pubmed ID
1710517Scopus ID
2-s2.0-0025863594 (requires institutional sign-in at Scopus site) 87 CitationsAbstract
Recent studies have shown that antibodies characteristic of quinine- and quinidine-induced thrombocytopenia sometimes recognize the platelet membrane glycoprotein (GP) complex IIb/IIIa in addition to their well known target, GPIb/IX. We have investigated the frequency with which drug-induced antibodies bind to GPIIb/IIIa and the nature of their target epitopes. In studies of sera from 13 patients sensitive to quinidine or quinine, we found that 10 contained IgG antibodies specific for both GPIb/IX and GPIIb/IIIa, two reacted with GPIb/IX alone, and one reacted with GPIIb/IIIa alone. In all cases, the presence of drug was required for binding of IgG to target GPs. By immunoabsorption, we found that each of five polyspecific sera contained at least two different antibodies, one reactive with GPb/IX and the other with GPIIb/IIIa. Further studies with eight drug-dependent antibodies (DDAb) specific for GPIIb/IIIa showed that three recognized the GPIIb/IIIa complex only, one recognized GPIIb alone, and three recognized GPIIIa alone. The eighth serum appeared to bind to both GPIIIa alone and to an epitope determined by the GPIIb/IIIa complex. The three antibodies specific for GPIIIa alone also reacted with GPIIIa deglycosylated with endo-H, and with the major (61 Kd) fragment obtained by chymotryptic digestion of GPIIIa but failed to react with reduced GPIIIa. These findings demonstrate that, in drug-induced, immunologic thrombocytopenia, the anti-platelet immune response is typically directed against epitopes on both GPIb/IX and GPIIb/IIIa. The three DDAb we studied that were specific for GPIIIa alone recognize epitopes resistant to chymotrypsin and endo-H treatment that are dependent on intrachain disulfide bonding.
Author List
Visentin GP, Newman PJ, Aster RHMESH terms used to index this publication - Major topics in bold
AnimalsAutoantibodies
Chymotrypsin
Epitopes
Humans
Immunoblotting
Immunoglobulin G
Immunosorbent Techniques
Mice
Peptide Fragments
Platelet Membrane Glycoproteins
Quinidine
Quinine
Thrombocytopenia
