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) 27 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 RHAuthor
Richard H. Aster MD Professor in the Medicine department at Medical College of WisconsinMESH 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
