A novel lymphocyte toxicity assay to assess drug hypersensitivity syndromes

Objectives: To validate the novel lymphocyte toxicity assay (LTA) based on the mitochondrial succinate dehydrogenase (SDH) activity vs, the LTA by usi ng trypan blue exclusion and to determine the utility of the assay to confi rm drug hypersensitivity syndrome (DHS) to sulphonamides (SMX) and aromatic anticonvulsants. Methods: Incubation of patient lymphocytes, with or without murine hepatic microsomes with anticonvulsants or SMX. The viability of lymphocytes was ba sed on SDH activity that can be measured spectrophotometrically. The percen tage of cells displaying cytotoxicity compared to controls (cells treated o nly with drug) was calculated. Seventy-two immunocompetent and 16 immunocom promised (HIV) patients with DHS to SMX were sampled. The results were vali dated vs. 26 controls that had not experienced DHS to SMX. Sixty-two patien ts who had DHS to anticonvulsants were compared with 24 controls that did n ot have any DHS to the same anticonvulsants. Results: The results showed a very good percentage of sensitivity 98 and sp ecificity 96 with a kappa -score of 0.96. LTA higher than 13.5% was conside red positive for the immunocompetent population and LTA higher than 22% was positive for the immunocompromised population. In two of the 26 controls, LTA was positive. Conclusion: The high quantitative kappa -value 0.96 emphasizes that the nov el LTA is at least as good as the trypan blue assay. The latter is labor in tensive, time consuming, and prone to human error. The new assay is objecti ve, faster, and has been reproducible in assessing cytotoxicity. Copyright (C) 2000 The Canadian Society of Clinical Chemists.