The predictive value of the in vitro platelet toxicity assay (iPTA) for the diagnosis of hypersensitivity reactions to sulfonamides: a case-control study

摘要

BackgroundDrug hypersensitivity reactions (DHRs) are rare butpotentially fatal types of adverse drug reactions (ADRs)that develop in susceptible patients following exposureto certain drugs including sulfonamides. The diagnosisof this type of ADRs is challenging and currentlydepends on clinical expertise. A safe and reliable in vitrotest to diagnose DHRs would be a major advance inpatient care and in evaluation of possible serious ADRsduring drug development and clinical trials. Currentavailable in vitro tests including the lymphocyte toxicityassay (LTA) and the lymphocyte transformation test(LTT) are cumbersome and expensive, and their predictivevalues are undefined. We have recently developed a novelin vitro diagnostic test for DHRs, the in vitro platelet toxicityassay (iPTA) to test patient susceptibility to DHS. Theaim of this study was to evaluate the predictive value ofthe iPTA in diagnosis of DHRs to sulfonamide antibiotics.MethodWe have recruited 66 individuals (36 DHS-sulfa patientsand 30 healthy controls) to participate in the study. TheDHR cases were referred and diagnosed based on rigorousinternationally accepted criteria. Blood samples wereobtained and both LTA and iPTA were performedindependently. Results were then analyzed to determinethe degree of agreement between the likelihood of theoccurrence of the reaction as determined clinically and theperformance of the two diagnostic approaches.ResultsThere was concentration-dependent toxicity in the cells ofpatients when incubated with the reactive hydroxylaminemetabolite of sulfamethoxazole for both the LTA andiPTA (p<0.05) and toxicity was significantly greater for thecells of patients versus controls (p<0.05). The tests had ahigh degree of agreement (correlation coefficient: R2 =0.97). The iPTA was significantly more sensitive than theconventional LTA test in detecting the susceptibility ofpatient cells to in vitro toxicity (p<0.05).ConclusionThe novel iPTA has considerable potential as an investigativetool for DHS as it is cheaper to perform and requiresno special reagents that make it an excellent candidate forwider use. The iPTA has also a greater sensitivity indetecting patients with predisposition to develop DHRs tosulfonamides and other drugs and thus can be used toscreen for susceptible patients prior to drug prescribingand during drug development process.