PMID- 16861345 OWN - NLM STAT- MEDLINE DCOM- 20061005 LR - 20210206 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 108 IP - 3 DP - 2006 Aug 1 TI - Patients with quinine-induced immune thrombocytopenia have both "drug-dependent" and "drug-specific" antibodies. PG - 922-7 AB - Immune thrombocytopenia induced by quinine and many other drugs is caused by antibodies that bind to platelet membrane glycoproteins (GPs) only when the sensitizing drug is present in soluble form. In this disorder, drug promotes antibody binding to its target without linking covalently to either of the reacting macro-molecules by a mechanism that has not yet been defined. How drug provides the stimulus for production of such antibodies is also unknown. We studied 7 patients who experienced severe thrombocytopenia after ingestion of quinine. As expected, drug-dependent, platelet-reactive antibodies specific for GPIIb/IIIa or GPIb/IX were identified in each case. Unexpectedly, each of 6 patients with GPIIb/IIIa-specific antibodies was found to have a second antibody specific for drug alone that was not platelet reactive. Despite recognizing different targets, the 2 types of antibody were identical in requiring quinine or desmethoxy-quinine (cinchonidine) for reactivity and in failing to react with other structural analogues of quinine. On the basis of these findings and previous observations, a model is proposed to explain drug-dependent binding of antibodies to cellular targets. In addition to having implications for pathogenesis, drug-specific antibodies may provide a surrogate measure of drug sensitivity in patients with drug-induced immune cytopenia. FAU - Bougie, Daniel W AU - Bougie DW AD - Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, USA. dan.bougie@bcw.edu FAU - Wilker, Peter R AU - Wilker PR FAU - Aster, Richard H AU - Aster RH LA - eng GR - R01 HL013629/HL/NHLBI NIH HHS/United States GR - HL-13629/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies) RN - 0 (Platelet Glycoprotein GPIIb-IIIa Complex) RN - 0 (Platelet Glycoprotein GPIb-IX Complex) RN - 0 (Platelet Membrane Glycoproteins) RN - 0 (glycoprotein receptor GPIb-IX) RN - A7V27PHC7A (Quinine) SB - IM MH - Antibodies/*blood MH - Humans MH - Immunoassay MH - Platelet Glycoprotein GPIIb-IIIa Complex/immunology MH - Platelet Glycoprotein GPIb-IX Complex/immunology MH - Platelet Membrane Glycoproteins/immunology MH - Quinine/*adverse effects/analogs & derivatives/*immunology MH - Thrombocytopenia/*chemically induced/immunology PMC - PMC1895854 EDAT- 2006/07/25 09:00 MHDA- 2006/10/06 09:00 PMCR- 2007/08/01 CRDT- 2006/07/25 09:00 PHST- 2006/07/25 09:00 [pubmed] PHST- 2006/10/06 09:00 [medline] PHST- 2006/07/25 09:00 [entrez] PHST- 2007/08/01 00:00 [pmc-release] AID - S0006-4971(20)52744-4 [pii] AID - 0922 [pii] AID - 10.1182/blood-2006-01-009803 [doi] PST - ppublish SO - Blood. 2006 Aug 1;108(3):922-7. doi: 10.1182/blood-2006-01-009803.