Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

Bougie, Daniel W.; Birenbaum, Jessica; Rasmussen, Mark A.; Poncz, Mortimer; Aster, Richard H.

doi:10.1182/blood-2008-09-177279

Cited by 20 publications

(36 citation statements)

References 39 publications

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“…27 Details of the immunization protocol and selection for hybridomas secreting ␣ IIb /␤ 3 -specific mAbs have been described previously. 28 Other mAbs used were 10E5 (anti-␣ IIb ) from B. S. Coller (Rockefeller University), 7E3 (anti-␤ 3 ) from Centocor Inc, AP3 (anti-␤ 3 ) and AP2 (anti-␣ IIb /␤ 3 ) from the Hybridoma Core Laboratory (Blood Research Institute). mAbs were biotinylated with sulfo-NHS-LC-Biotin (Pierce Biotechnology) according to the manufacturer's protocol.…”

Section: Mabsmentioning

confidence: 99%

“…28 mAbs were mapped to the ␣ or ␤ subunit of ␣ IIb /␤ 3 on the basis of their reactions with CHO cell lines expressing human ␣ IIb paired with rat ␤ 3 or vice versa. After assignment to an ␣ or ␤ subunit, the mAbs were mapped to the ␤ propeller domain of ␣ IIb or the ␤ A domain of ␤ 3 on the basis of their reactions with CHO cells expressing ␣ IIb /␤ 3 that was human except for substitution of a rat sequence in one of these domains.…”

Section: Mapping Of Mab-binding Sites To Specific Domains Of ␣ Iib Anmentioning

confidence: 99%

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Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

Bougie

Rasmussen

Zhu

et al. 2012

Blood

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Section: Mabsmentioning

confidence: 99%

Section: Mapping Of Mab-binding Sites To Specific Domains Of ␣ Iib Anmentioning

confidence: 99%

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

Bougie

Rasmussen

Zhu

et al. 2012

Blood

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“…7 In this and other respects, 314.1 closely mimics the behavior of antibodies that cause platelet destruction in patients with quinine-induced immune thrombocytopenia. To test the feasibility of using the NOD/scid mouse model to demonstrate drug-dependent, antibody-mediated platelet clearance, mice previously infused with human platelets were injected intraperitoneally with 50 g mAb 314.1 followed by 74 g quinine or buffer.…”

Section: Resultsmentioning

confidence: 85%

“…7,9,10 In brief, 5 ϫ 10 6 washed platelets For personal use only. on April 29, 2019. by guest www.bloodjournal.org From suspended in phosphate-buffered saline containing 1% bovine serum albumin were incubated with antibody in a total volume of 50 L for 60 minutes at room temperature and washed twice in bovine serum albumin-phosphate-buffered saline.…”

Section: Flow Cytometrymentioning

confidence: 99%

Drug-dependent clearance of human platelets in the NOD/scid mouse by antibodies from patients with drug-induced immune thrombocytopenia

Bougie

Nayak

Boylan

et al. 2010

Blood

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Drug-induced immune thrombocytopenia (DITP) is a relatively common and sometimes life-threatening condition caused by antibodies that bind avidly to platelets only when drug is present. How drugdependent antibodies (DDAbs) are induced and how drugs promote their interaction with platelets are poorly understood, and methods for detecting DDAbs are suboptimal. A small animal model of DITP could provide a new tool for addressing these and other questions concerning pathogenesis and diagnosis. We examined whether the nonobese diabetic/ severe combined immunodeficient (NOD/ scid) mouse, which lacks xenoantibodies and therefore allows infused human platelets to circulate, can be used to study drug-dependent clearance of platelets by DDAbs in vivo. In this report, we show that the NOD/scid model is suitable for this purpose and describe studies to optimize its sensitivity for drug-dependent human antibody detection. We further show that the mouse can produce metabolites of acetaminophen and naproxen for which certain drug-dependent antibodies are specific in quantities sufficient to enable these antibodies to cause platelet destruction. The findings indicate that the NOD/ scid mouse can provide a unique tool for studying DITP pathogenesis and may be particularly valuable for identifying metabolite-specific antibodies capable of causing immune thrombocytopenia or hemolytic anemia. (Blood. 2010;116(16): 3033-3038) IntroductionDrug-induced immune thrombocytopenia (DITP) can be triggered by various medications through several distinct mechanisms. 1,2 In a comprehensive survey of DITP cases reported since 1998, George and coworkers identified 17 drugs that were considered to be "probable" causes of DITP and 51 thought to be "definite" causes on the basis of having met, respectively, 3 or 4 well-defined clinical criteria. 3,4 This analysis has helped greatly to define which drugs are capable of causing DITP but does not provide proof in an individual patient that a particular drug was responsible. Evidence supporting a cause-and-effect relationship between drug exposure and thrombocytopenia can be obtained by identifying a drugdependent antibody (DDAb) that reacts with platelets only when the implicated drug is present. 1,2,5 However, relatively few laboratories are experienced in DDAb detection, and it is not rare for antibody testing to be negative in a patient with a clinical history strongly suggestive of DITP. 1,2 Moreover, there is not uniform agreement as to whether detection of a DDAb provides conclusive evidence that the antibody caused platelet destruction. Partly for these reasons, identification of a DDAb is not included among the George criteria. The most stringent of these criteria calls for thrombocytopenia to recur when a patient is exposed a second time to the implicated drug. 3 While a rechallenge can provide convincing evidence that thrombocytopenia was drug-induced, it is often impractical and can be difficult to justify for reasons of patient safety.A surrogate small animal model for direct demonstration...

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“…The HDAb mechanism is often suspected in DITP in laboratory and companion animals, but supportive data have been lacking. Recent investigative and mechanistic studies indicate that the HDAb mechanism may be rare in DITP (Visentin and Liu 2007;Bougie et al 2009). As with humans, other mechanisms (e.g., formation of drug-dependent antibodies [DDAb]) may be the more likely pathway in many incidences of laboratory and companion animal DITP.…”

Section: Hapten-dependent Antibodies (Hdab)mentioning

confidence: 99%

Review of Continuing Education Course on Hemostasis

Baker

Brassard

2010

Toxicol Pathol

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The continuing education course ''Hemostasis'' provided a comprehensive review of hemostasis and selected perturbations of the underlying processes as well as an assessment of hemostasis in animal models and preclinical testing environments. The session began with a review of the current state of understanding of hemostasis and how the waterfall or cascade of activation has transformed to the current cell-based, membraneassociated sequence of highly regulated events. The specific mechanisms of drug-induced thrombocytopenia were then presented, followed by a discussion of the relationships of coagulation and platelets in inflammation and cancer metastasis and platelet activity. Evaluation of hemostasis and platelet function in animals and especially in the environment of the contract research facility concluded the session.

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Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia

Cited by 20 publications

References 39 publications

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

Drug-dependent clearance of human platelets in the NOD/scid mouse by antibodies from patients with drug-induced immune thrombocytopenia

Review of Continuing Education Course on Hemostasis

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