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

Abstract

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.

• Authors: Jettanong Klaewsongkram, Supranee Buranapraditkun, Pattarawat Thantiworasit, Pawinee Rerknimitr, Papapit Tuchinda, Leena Chularojanamontri, Ticha Rerkpattanapipat, Kumutnart Chanprapaph, Wareeporn Disphanurat, Panlop Chakkavittumrong, Napatra Tovanabutra, Chutika Srisuttiyakorn, Yuttana Srinoulprasert, Chonlaphat Sukasem, Yuda Chongpison
• Journal: Allergy, asthma & immunology research (Allergy Asthma Immunol Res) Vol. 13 Issue 6 Pg. 896-907 (Nov 2021) ISSN: 2092-7355 [Print] Korea (South)
• PMID: 34734507 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.