The lymphocyte transformation test (LTT) is used for the in vitro detection of a drug sensitization in assumed drug allergic patients. It is based on the detection of antigen (drug)-specific activation of T cells indicated by e.g. proliferation or cytokine secretion. However, occasional stimulatory effects of the drug unrelated to specific drug-allergic mechanisms can only be detected if a larger number of non-drug allergic control persons are tested with this specific drug. In this respect, the overall specificity of the LTT with ELISA read-out is summarized in several review articles, but the impact of a specific drug on the specificity has not yet been analyzed in a larger set of control persons.
Do amoxicillin, cefuroxime and clindamycin induce an IFN-y or IL-5 secretion of PBMC from control persons using the LTT with ELISA read-out?
We performed LTTs with amoxicillin, cefuroxime and clindamycin as culprit drug determining drug-specific interferon (IFN)-y and interleukin (IL)-5 secretion measured by ELISA read-out. We included PBMCs from 60 non-drug allergic control persons, which were unexposed to the tested drug at the time of blood donation.
PBMCs from 12 out of 23 control persons tested with amoxicillin gave a positive stimulation index (SI > 3.0) for IFN-γ resulting in a specificity of 47.8%. The corresponding specificity was 75% for cefuroxime (5/20 if SI > 3.0) and 58.8% for clindamycin (7/17, if SI > 2.0), respectively. In a next step, we calculated the Δ IFN-y concentration by subtracting the background IFN-γ concentration in the unstimulated sample from the stimulated sample. After stimulation with amoxicillin a mean concentration of 7.4 pg/mL IFN-γ was secreted. The less outlier prone median concentration was 7.4 pg/ml and much higher than for cefuroxime (1.7 pg/mL) and clindamycin (1.0 pg/mL). Remarkably, IL-5 concentrations were below the detection limit (< 1 pg/ml) for all drugs in all control persons who responded to TT.
A positive LTT result in a control patient may challenge the validity of a positive LTT result in the same experiment for a patient with assumed drug allergy.
Copyright © 2023. Published by Elsevier B.V.
