Drug-dependent clearance of human platelets in the NOD/scid mouse by antibodies from patients with drug-induced immune thrombocytopenia. Blood 2010 Oct 21;116(16):3033-8
Date
07/01/2010Pubmed ID
20587782Pubmed Central ID
PMC2974608DOI
10.1182/blood-2010-03-277764Scopus ID
2-s2.0-77958183435 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
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 drug-dependent 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.
Author List
Bougie DW, Nayak D, Boylan B, Newman PJ, Aster RHMESH terms used to index this publication - Major topics in bold
Analgesics, Non-NarcoticAnimals
Anti-Infective Agents
Antibodies
Antibodies, Monoclonal
Blood Platelets
Cell Survival
Disease Models, Animal
Humans
Mice
Mice, SCID
Quinine
Sulfamethoxazole
Thrombocytopenia