Medical College of Wisconsin
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Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia. Blood 2009 Jan 29;113(5):1105-11 PMID: 18948570 PMCID: PMC2635075

Pubmed ID

18948570

DOI

10.1182/blood-2008-09-177279

Abstract

Drug-induced immune thrombocytopenia (DITP) is caused by drug-dependent antibodies (DDAbs) that are nonreactive in themselves but bind tightly to specific platelet membrane glycoproteins (GP) when soluble drug is present at pharmacologic concentrations. This reaction takes place without covalent linkage of drug to the target, indicating that drug does not function as a classical hapten to promote antibody binding. Studies to define other mechanism(s) responsible for this interaction have been frustrated by the polyclonal nature of human DDAbs and limited quantities of antibody usually available. We produced 2 monoclonal antibodies (mAbs), 314.1 and 314.3, from a mouse immunized with purified human GPIIb/IIIa and quinine that recognize the N terminus of the GPIIb beta propeller domain only when soluble quinine is present. Both monoclonals closely mimic the behavior of antibodies from patients with quinine-induced immune thrombo-cytopenia in their reactions at various concentrations of quinine and quinine congeners. Sequencing studies showed that the 2 mAbs are closely related structurally and that mAb 314.3 probably evolved from mAb 314.1 in the course of the immune response. These monoclonal reagents are the first of their kind and should facilitate studies to define the molecular basis for drug-dependent antibody binding and platelet destruction in DITP.

Author List

Bougie DW, Birenbaum J, Rasmussen M, Poncz M, Aster RH

Author

Richard H. Aster MD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-60849113420   19 Citations

MESH terms used to index this publication - Major topics in bold

Analgesics, Non-Narcotic
Animals
Antibodies, Monoclonal
Autoantibodies
Blood Platelets
CHO Cells
Cricetinae
Cricetulus
Humans
Mice
Platelet Glycoprotein GPIIb-IIIa Complex
Protein Structure, Tertiary
Purpura, Thrombocytopenic, Idiopathic
Quinine
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e