The Cyto-LTT: A multiplex cytokine assay to detect and assess the strength of T cell reactivity in drug hypersensitivity.
Publisher DOI
PubMed ID
41093699
Abstract
Background
The conventional in vitro lymphocyte transformation test (LTT) for diagnosing drug hypersensitivity reactions (DHRs) is limited by low sensitivity. To improve detection and assess T cell activation strength, we adapted this test to a cytokine-based assay (Cyto-LTT) by measuring IL-5, IL-13, IFN-γ, granzyme B and granulysin secretion.
Methods
We retrospectively analyzed 851 positive Cyto-LTT results (from a total 6058 Cyto-LTT) from a Swiss drug hypersensitivity diagnostic laboratory's database, including 97 patients with Drug Rash with Eosinophilia and Systemic Symptoms (DReSS) and 754 patients with exanthems, including urticarial, maculo- and maculopapular-rash. Cytokine responses measured across three drug concentrations of amoxicillin (n = 734), aromatic sulfonamides (n = 81), or vancomycin (n = 36) were evaluated for dose-dependency and the correlation to the clinical manifestations. A grading system defined strong responses as cytokine stimulation indices (SI) above the 75th percentile (per cytokine) in the exanthem group which served as a comparator for the DReSS cases.
Results
Cytokine responses increased dose-dependently. DReSS cases exhibited significantly stronger cytokine secretions compared to exanthem cases (p < 0.001), with strong responses observed in 62.9 % of DReSS patients versus 33.6 % of exanthem cases.
Conclusions
Cyto-LTT reveals dose-dependent T cell activation in delayed drug hypersensitivity reactions, challenging the notion that drug allergic reactions are dose-independent. The assay not only identifies the culprit drug but also quantifies immune activation strength. Stronger responses were more frequent in DReSS, suggesting the test may also inform risk assessment-particularly in guiding caution with structurally related compounds or in patients at risk for severe or recurrent reactions.
The conventional in vitro lymphocyte transformation test (LTT) for diagnosing drug hypersensitivity reactions (DHRs) is limited by low sensitivity. To improve detection and assess T cell activation strength, we adapted this test to a cytokine-based assay (Cyto-LTT) by measuring IL-5, IL-13, IFN-γ, granzyme B and granulysin secretion.
Methods
We retrospectively analyzed 851 positive Cyto-LTT results (from a total 6058 Cyto-LTT) from a Swiss drug hypersensitivity diagnostic laboratory's database, including 97 patients with Drug Rash with Eosinophilia and Systemic Symptoms (DReSS) and 754 patients with exanthems, including urticarial, maculo- and maculopapular-rash. Cytokine responses measured across three drug concentrations of amoxicillin (n = 734), aromatic sulfonamides (n = 81), or vancomycin (n = 36) were evaluated for dose-dependency and the correlation to the clinical manifestations. A grading system defined strong responses as cytokine stimulation indices (SI) above the 75th percentile (per cytokine) in the exanthem group which served as a comparator for the DReSS cases.
Results
Cytokine responses increased dose-dependently. DReSS cases exhibited significantly stronger cytokine secretions compared to exanthem cases (p < 0.001), with strong responses observed in 62.9 % of DReSS patients versus 33.6 % of exanthem cases.
Conclusions
Cyto-LTT reveals dose-dependent T cell activation in delayed drug hypersensitivity reactions, challenging the notion that drug allergic reactions are dose-independent. The assay not only identifies the culprit drug but also quantifies immune activation strength. Stronger responses were more frequent in DReSS, suggesting the test may also inform risk assessment-particularly in guiding caution with structurally related compounds or in patients at risk for severe or recurrent reactions.
Date Issued
2026-04
Publication Type
Article
Subject(s)
Subjects
Cytokine
•
Drug hypersensitivity
•
Drug-induced hypersensitivity syndrome
•
T cells
•
T lymphocytes
Language(s)
en
Additional Credits
Journal
Allergology International
Publisher
Elsevier
ISSN
1440-1592
1323-8930
Access(Rights)
open.access