Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa

Bougie, Daniel W.; Peterson, Julie A.; Rasmussen, Mark A.; Aster, Richard H.

doi:10.1182/blood-2015-04-643148

Cited by 26 publications

(20 citation statements)

References 52 publications

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“…Quinine has been commonly studied to understand the molecular mechanisms of drug-dependent antibody formation [31][32][33]. Quinine-dependent antibodies may be derived from a pool of naturally-occurring antibodies that are weakly reactive with autologous proteins [31,33].…”

Section: Nonementioning

confidence: 99%

“…Quinine-dependent antibodies may be derived from a pool of naturally-occurring antibodies that are weakly reactive with autologous proteins [31,33]. Quinine may have unique amphipathic properties that allow it to become integrated into complementaritydetermining regions of naturally occurring antibodies, creating a hybrid paratope that greatly increases binding affinity to cell surface antigens [32].…”

Section: Nonementioning

confidence: 99%

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Diversity and severity of adverse reactions to quinine: A systematic review

et al. 2016

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Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of druginduced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immunemediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered.

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Section: Nonementioning

confidence: 99%

Section: Nonementioning

confidence: 99%

Diversity and severity of adverse reactions to quinine: A systematic review

et al. 2016

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“…1,2 I n DITP, a drug somehow induces a tight interaction of antibody with one's own platelet antigen, leading to drug-dependent depletion of platelets. 3 In the absence of the drug, the antibody does not bind to the platelet with sufficient affinity to cause pathological damage.…”

Section: Renhao LI Emory University School Of Medicinementioning

confidence: 99%

“…The quinine-induced conformational change appears to be the molecular basis for the quinine-facilitated binding of 314 antibodies, as Bougie et al reported that the binding affinity of 314.1 antibody for purified integrin a IIb b 3 in the presence of quinine was 5 times tighter than that in the absence of quinine. 2 The quinine/314-antibody structures also point to an interesting possibility regarding the origin of drug-dependent antibodies; quinine may fit, perhaps by chance, into a preexisting antibody to either greatly improve its affinity for a platelet antigen or enable its recognition of a different antigen. Bougie et al 2 reported that 314.1 antibody with quinine bound 2 copies of a IIb b 3 on the platelet, as its apparent affinity for the platelet was orders of magnitude higher than that for the purified monovalent a IIb b 3 .…”

Section: Renhao LI Emory University School Of Medicinementioning

confidence: 99%

Expanding the binding model of DITP

2015

Blood

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“…Various in vitro assays have been developed to assess the risk of mAb drug-mediated thrombocytopenia. One of the commonly used methods is measuring direct binding of the mAb drugs in platelets by flow cytometry, surface plasmon resonance (SPR), or ELISA (Bougie, Peterson, Rasmussen, & Aster, 2015;Santostefano et al, 2012). A mAb drug candidate that can bind to platelets is generally expected to increase the risk of platelet phagocytosis through recognition of either the bound drug itself (if the drug contains an effective Fc portion) and/or via anti-drug antibodies that can potentially develop in vivo.…”

mentioning

confidence: 99%

In Vitro Monocyte/Macrophage Phagocytosis Assay for the Prediction of Drug‐Induced Thrombocytopenia

Narayanan

2019

CP Toxicology

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Phagocytosis of platelets by monocytes and macrophages is a primary mechanism of platelet clearance in vivo and has been increasingly implicated in playing an important role in thrombocytopenia mediated by monoclonal antibodies intended for therapeutic purposes. In the present article, we describe an in vitro flow cytometry assay to assess the effect of antibody-mediated platelet phagocytosis by monocytes. Freshly isolated platelets were labeled with a fluorescent probe, 5-chloromethylfluorescein diacetate (CMFDA) and then co-cultured with isolated peripheral blood mononuclear cells (PBMCs) from the same donor in the presence of increasing concentrations of a monoclonal antibody drug. After incubation, an increase in CMFDA fluorescence intensity of CD14 positive monocytes was evaluated by flow cytometry as an assessment for drug-mediated platelet phagocytosis by monocytes. The assay has been evaluated using both human and cynomolgus monkey cells for the prediction of drug-induced thrombocytopenia. C 2019 by John Wiley & Sons, Inc.

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Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa

Abstract: Key Points Drug-induced modulation of antibody specificity appears to explain the binding of drug-dependent mAbs to αIIb/β3 integrin. Drug-dependent platelet antibodies differ greatly from classic hapten-specific antibodies and may be induced by a quite different mechanism.

Cited by 26 publications

References 52 publications

Diversity and severity of adverse reactions to quinine: A systematic review

Diversity and severity of adverse reactions to quinine: A systematic review

Expanding the binding model of DITP

In Vitro Monocyte/Macrophage Phagocytosis Assay for the Prediction of Drug‐Induced Thrombocytopenia

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