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

Abstract

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.

• Authors: Daniel W Bougie, Dhirendra Nayak, Brian Boylan, Peter J Newman, Richard H Aster
• Journal: Blood (Blood) Vol. 116 Issue 16 Pg. 3033-8 (Oct 21 2010) ISSN: 1528-0020 [Electronic] United States
• PMID: 20587782 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Anti-Infective Agents
• Antibodies
• Antibodies, Monoclonal
• Quinine
• Sulfamethoxazole

Topics

• Analgesics, Non-Narcotic (immunology)
• Animals
• Anti-Infective Agents (immunology)
• Antibodies (adverse effects, immunology)
• Antibodies, Monoclonal (adverse effects, immunology)
• Blood Platelets (immunology)
• Cell Survival
• Disease Models, Animal
• Humans
• Mice
• Mice, SCID
• Quinine (immunology)
• Sulfamethoxazole (immunology)
• Thrombocytopenia (chemically induced, immunology)