title: 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.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA. Dan.bougie@bcw.edu
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bougie
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Nayak
authors.forename: Brian
authors.initials: B
authors.lastname: Boylan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Newman
authors.forename: Richard H
authors.initials: RH
authors.lastname: Aster
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000276:immunology; D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology; D000906:Antibodies / Q000009:adverse effects* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D011803:Quinine / Q000276:immunology; D013420:Sulfamethoxazole / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology*
chemical_list: D018712:Analgesics, Non-Narcotic; D000890:Anti-Infective Agents; D000906:Antibodies; D000911:Antibodies, Monoclonal; D011803:Quinine; D013420:Sulfamethoxazole