title: The predictive value of the in vitro platelet toxicity assay (iPTA) for the diagnosis of hypersensitivity reactions to sulfonamides.
abstract: Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte toxicity assay (LTA) have been used but are time-consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet toxicity assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS-sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration-dependent toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents.
authors.affiliation: Ivey Chair in Molecular Toxicology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Abdelbaset A
authors.initials: AA
authors.lastname: Elzagallaai
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rieder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D016022:Case-Control Studies; D002648:Child; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D013449:Sulfonamides; C059873:sulfamethoxazole hydroxylamine; D013420:Sulfamethoxazole