Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients

© 2018 Elsevier B.V. Phenytoin (PHE) and carbamazepine (CBZ) are first rank causative drugs that can induce drug rash with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Identification of anti-epileptic drugs as a culprit drug has been p...

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Main Authors: Pongsathorn Kumkamthornkul, Somkiat Udnaen, Tunsuda Tansit, Papapit Tuchinda, Yuttana Srinoulprasert
Other Authors: Faculty of Medicine, Siriraj Hospital, Mahidol University
Format: Article
Published: 2019
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/45959
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spelling th-mahidol.459592019-08-28T13:48:05Z Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients Pongsathorn Kumkamthornkul Somkiat Udnaen Tunsuda Tansit Papapit Tuchinda Yuttana Srinoulprasert Faculty of Medicine, Siriraj Hospital, Mahidol University Immunology and Microbiology Medicine Pharmacology, Toxicology and Pharmaceutics © 2018 Elsevier B.V. Phenytoin (PHE) and carbamazepine (CBZ) are first rank causative drugs that can induce drug rash with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Identification of anti-epileptic drugs as a culprit drug has been problematic; hence, in vitro tests could be promising methods to define causative drugs without clinical risk. The aim of this study is to evaluate the efficacy of lymphocyte transformation tests (LTT) and cytokine detection assays in identifying PHE and CBZ as culprit drugs. Peripheral blood mononuclear cells were collected from normal, PHE/CBZ tolerance and PHE/CBZ hypersensitivity cohorts and utilized for cell-culture assays. LTT was performed and culture supernatants were subjected to multiple cytokine detection assays. Our study showed that LTT correlated with outcomes of Naranjo's assessment with statistical significance (r = 0.614). Various sensitivities of LTT and cytokine detection assays were demonstrated. Although both assays provided excellent specificity, LTT yielded higher sensitivity as compared to those of cytokine detection assays in both DRESS and SJS/TEN. Regardless whether specificity is, this is the first report to demonstrate that IL-4 detection assay could enhance sensitivity to identify culprit drug when it was combined with LTT for SJS/TEN patients or it was combined with IL-2/IFN-γ detection assays for DRESS ones. 2019-08-23T11:17:22Z 2019-08-23T11:17:22Z 2018-10-01 Article International Immunopharmacology. Vol.63, (2018), 204-210 10.1016/j.intimp.2018.08.010 18781705 15675769 2-s2.0-85051121994 https://repository.li.mahidol.ac.th/handle/123456789/45959 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85051121994&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Immunology and Microbiology
Medicine
Pharmacology, Toxicology and Pharmaceutics
spellingShingle Immunology and Microbiology
Medicine
Pharmacology, Toxicology and Pharmaceutics
Pongsathorn Kumkamthornkul
Somkiat Udnaen
Tunsuda Tansit
Papapit Tuchinda
Yuttana Srinoulprasert
Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients
description © 2018 Elsevier B.V. Phenytoin (PHE) and carbamazepine (CBZ) are first rank causative drugs that can induce drug rash with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Identification of anti-epileptic drugs as a culprit drug has been problematic; hence, in vitro tests could be promising methods to define causative drugs without clinical risk. The aim of this study is to evaluate the efficacy of lymphocyte transformation tests (LTT) and cytokine detection assays in identifying PHE and CBZ as culprit drugs. Peripheral blood mononuclear cells were collected from normal, PHE/CBZ tolerance and PHE/CBZ hypersensitivity cohorts and utilized for cell-culture assays. LTT was performed and culture supernatants were subjected to multiple cytokine detection assays. Our study showed that LTT correlated with outcomes of Naranjo's assessment with statistical significance (r = 0.614). Various sensitivities of LTT and cytokine detection assays were demonstrated. Although both assays provided excellent specificity, LTT yielded higher sensitivity as compared to those of cytokine detection assays in both DRESS and SJS/TEN. Regardless whether specificity is, this is the first report to demonstrate that IL-4 detection assay could enhance sensitivity to identify culprit drug when it was combined with LTT for SJS/TEN patients or it was combined with IL-2/IFN-γ detection assays for DRESS ones.
author2 Faculty of Medicine, Siriraj Hospital, Mahidol University
author_facet Faculty of Medicine, Siriraj Hospital, Mahidol University
Pongsathorn Kumkamthornkul
Somkiat Udnaen
Tunsuda Tansit
Papapit Tuchinda
Yuttana Srinoulprasert
format Article
author Pongsathorn Kumkamthornkul
Somkiat Udnaen
Tunsuda Tansit
Papapit Tuchinda
Yuttana Srinoulprasert
author_sort Pongsathorn Kumkamthornkul
title Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients
title_short Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients
title_full Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients
title_fullStr Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients
title_full_unstemmed Evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy patients
title_sort evaluation of a lymphocyte transformation test and cytokine detection assay to identify phenytoin and carbamazepine provoked dress or sjs/ten in epilepsy patients
publishDate 2019
url https://repository.li.mahidol.ac.th/handle/123456789/45959
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