Exploring cytokine outputs for ex vivo diagnostics in drug reaction with eosinophilia and systemic symptoms (DRESS)

Background: In an exploratory study to assess the potential to individualize T-cell diagnostics in antibiotic-associated severe T-cell mediated hypersensitivity, we focused on drug reaction with eosinophilia and systemic symptoms (DRESS) and the related cytokine outputs IL-4 and IL-5.

Methods: Patients with well-phenotyped RegiSCAR ≥4 DRESS, positive intradermal skin testing, and a previous negative IFN-γ Enzyme-Linked ImmunoSpot (ELISpot) assay were prospectively recruited. We specifically performed an ELISpot assay with IL-4 and IL-5 cytokine outputs. As comparative controls, these cytokine outputs were performed simultaneously in patients with a positive ex vivo IFN-γ release ELISpot result.

Results: Four antibiotic-associated DRESS cases were included. The IL-4 and IL-5 output ELISpot assay demonstrated various results among these patients, with at least 1 cytokine present in all the cases. As for the 2 controls with known positive IFN-γ release, compared to the IFN-γ secretion, the cytokine output using IL-4 and IL-5 showed an increased positivity.

Conclusion: In patients where the early response has suggested a TH2 response such as DRESS, IL-4 and IL-5 cytokine outputs could present an investigational advantage, including when IFN-γ is negative. In the future, larger prospective studies are required to understand the role of varied cytokine outputs in T-cell-mediated hypersensitivities.