Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia.
Platelets coated with quinine- or quinidine-induced antibodies form rosettes around protein A-Sepharose beads and normal platelets form rosettes about protein A-Sepharose beads coated with these antibodies. These reactions occurred only in the presence of sensitizing drug. Platelets also formed rosettes about protein A-Sepharose beads coated with an anti-PIA1 antibody, but drug was not required. Formation of rosettes between antibody-coated platelets and protein A-Sepharose was inhibited by F(ab')2 fragments of goat antibody specific for the Fc portion of human IgG, while rosette formation between antibody-coated protein A-Sepharose and platelets was inhibited by F(ab')2 fragments directed against the F(ab')2 portion of the IgG molecule. Since binding of IgG to protein A is known to occur via the Fc region, these findings suggest that binding of drug-induced antibodies to platelets occurs at the Fab domains of the IgG molecule.
D000906:Antibodies / Q000378:metabolism*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D003864:Depression, Chemical; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D011485:Protein Binding; D011802:Quinidine / Q000009:adverse effects* / Q000276:immunology; D011803:Quinine / Q000009:adverse effects* / Q000276:immunology; D011947:Receptors, Antigen, B-Cell; D012397:Rosette Formation; D013205:Staphylococcal Protein A / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced*
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D011947:Receptors, Antigen, B-Cell; D013205:Staphylococcal Protein A; D011803:Quinine; D011802:Quinidine