Lymphocyte transformation test and cytokine detection assays: Determination of read out parameters for delayed-type drug hypersensitivity reactions

Abstract

Drug hypersensitivity reactions (DHRs) occur in certain people and are often not predictable. DHRs can be classified as immediate and delayed reactions regarding to onset of clinical manifestations. Both reactions are considered to be an important public health problem because they can lead to life-threatening conditions; however, this review article will focus on delayed DHRs. The most important points for diagnosis of delayed DHRs are the recognition of drug hypersensitivity characteristics and culprit drug identification. While it is usually difficult to identify a culprit drug; clinical evaluation using the causality assessment method, a non-invasive process, can identify the culprit drug without the need for intensive investigation. Delayed DHRs can cause life-threatening conditions; therefore, in vivo skin tests, as well as drug provocation tests, have to be cautiously performed by a drug allergist and have not been recommended in uncontrolled conditions. ENDA/EAACI has recommended that in vitro tests (if available) be performed prior to any in vivo tests. Therefore, in vitro diagnostic tests can be alternative methods to identify a culprit drug for delayed DHR diagnosis as there is no or very low risk for patients under investigation. There are many testing approaches to identify causative agents for delayed DHRs such as: the lymphocyte transformation test (LTT), cytokine/mediator detection assays (i.e. ELISA and flow cytometry-based bead assays), multiplex bead-based immunoassay and ELISpot. The LTT is the most standardized method whereas it has been available in medical schools affiliated with university hospitals. Other in vitro tests, like cytokine detection assays, have also been used, even though they are still being evaluated. They could supplement LTT results that would provide drug allergist's with documentary evidence and prevent risk to patients by avoiding in vivo or drug provocation testing. Hence, the in vitro tests have been promising tests contributing to the management of the delayed DHR work-up process in clinical practice.