Allergy, asthma & immunology research · 2021
The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions.
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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
Аннотация
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.
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.