Cargando…

The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions

PROPOSE: The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). METHODS: Frequencies of drug-induced interleukin-22 (IL-22)-, interfe...

Descripción completa

Detalles Bibliográficos
Autores principales: Klaewsongkram, Jettanong, Buranapraditkun, Supranee, Thantiworasit, Pattarawat, Rerknimitr, Pawinee, Tuchinda, Papapit, Chularojanamontri, Leena, Rerkpattanapipat, Ticha, Chanprapaph, Kumutnart, Disphanurat, Wareeporn, Chakkavittumrong, Panlop, Tovanabutra, Napatra, Srisuttiyakorn, Chutika, Srinoulprasert, Yuttana, Sukasem, Chonlaphat, Chongpison, Yuda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569031/
https://www.ncbi.nlm.nih.gov/pubmed/34734507
http://dx.doi.org/10.4168/aair.2021.13.6.896
_version_ 1784594561603993600
author Klaewsongkram, Jettanong
Buranapraditkun, Supranee
Thantiworasit, Pattarawat
Rerknimitr, Pawinee
Tuchinda, Papapit
Chularojanamontri, Leena
Rerkpattanapipat, Ticha
Chanprapaph, Kumutnart
Disphanurat, Wareeporn
Chakkavittumrong, Panlop
Tovanabutra, Napatra
Srisuttiyakorn, Chutika
Srinoulprasert, Yuttana
Sukasem, Chonlaphat
Chongpison, Yuda
author_facet Klaewsongkram, Jettanong
Buranapraditkun, Supranee
Thantiworasit, Pattarawat
Rerknimitr, Pawinee
Tuchinda, Papapit
Chularojanamontri, Leena
Rerkpattanapipat, Ticha
Chanprapaph, Kumutnart
Disphanurat, Wareeporn
Chakkavittumrong, Panlop
Tovanabutra, Napatra
Srisuttiyakorn, Chutika
Srinoulprasert, Yuttana
Sukasem, Chonlaphat
Chongpison, Yuda
author_sort Klaewsongkram, Jettanong
collection PubMed
description PROPOSE: The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). METHODS: Frequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses. RESULTS: Twenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of drug-induced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of drug-induced IFN-γ releasing cells. CONCLUSION: The measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02574988
format Online
Article
Text
id pubmed-8569031
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
record_format MEDLINE/PubMed
spelling pubmed-85690312021-11-17 The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions Klaewsongkram, Jettanong Buranapraditkun, Supranee Thantiworasit, Pattarawat Rerknimitr, Pawinee Tuchinda, Papapit Chularojanamontri, Leena Rerkpattanapipat, Ticha Chanprapaph, Kumutnart Disphanurat, Wareeporn Chakkavittumrong, Panlop Tovanabutra, Napatra Srisuttiyakorn, Chutika Srinoulprasert, Yuttana Sukasem, Chonlaphat Chongpison, Yuda Allergy Asthma Immunol Res Original Article PROPOSE: The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). METHODS: Frequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses. RESULTS: Twenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of drug-induced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of drug-induced IFN-γ releasing cells. CONCLUSION: The measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02574988 The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2021-09-15 /pmc/articles/PMC8569031/ /pubmed/34734507 http://dx.doi.org/10.4168/aair.2021.13.6.896 Text en Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Klaewsongkram, Jettanong
Buranapraditkun, Supranee
Thantiworasit, Pattarawat
Rerknimitr, Pawinee
Tuchinda, Papapit
Chularojanamontri, Leena
Rerkpattanapipat, Ticha
Chanprapaph, Kumutnart
Disphanurat, Wareeporn
Chakkavittumrong, Panlop
Tovanabutra, Napatra
Srisuttiyakorn, Chutika
Srinoulprasert, Yuttana
Sukasem, Chonlaphat
Chongpison, Yuda
The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions
title The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions
title_full The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions
title_fullStr The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions
title_full_unstemmed The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions
title_short The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions
title_sort role of in vitro detection of drug-specific mediator-releasing cells to diagnose different phenotypes of severe cutaneous adverse reactions
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569031/
https://www.ncbi.nlm.nih.gov/pubmed/34734507
http://dx.doi.org/10.4168/aair.2021.13.6.896
work_keys_str_mv AT klaewsongkramjettanong theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT buranapraditkunsupranee theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT thantiworasitpattarawat theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT rerknimitrpawinee theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT tuchindapapapit theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chularojanamontrileena theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT rerkpattanapipatticha theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chanprapaphkumutnart theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT disphanuratwareeporn theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chakkavittumrongpanlop theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT tovanabutranapatra theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT srisuttiyakornchutika theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT srinoulprasertyuttana theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT sukasemchonlaphat theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chongpisonyuda theroleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT klaewsongkramjettanong roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT buranapraditkunsupranee roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT thantiworasitpattarawat roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT rerknimitrpawinee roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT tuchindapapapit roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chularojanamontrileena roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT rerkpattanapipatticha roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chanprapaphkumutnart roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT disphanuratwareeporn roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chakkavittumrongpanlop roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT tovanabutranapatra roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT srisuttiyakornchutika roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT srinoulprasertyuttana roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT sukasemchonlaphat roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions
AT chongpisonyuda roleofinvitrodetectionofdrugspecificmediatorreleasingcellstodiagnosedifferentphenotypesofseverecutaneousadversereactions