In vitro rapid diagnostic tests for severe drug hypersensitivity reactions in children

Abstract

Background

Previous reports have demonstrated the utility of T-cell proliferation and cytokine release assays as in vitro diagnostic tests for drug causation in drug hypersensitivity reactions (DHR). However, data from pediatric populations are scarce compared with data in adults.

Objectives

To compare the lymphocyte proliferation assay (LPA) with combination cytokine assays in the pediatric population and to identify its potential use in the acute and postrecovery phases.

Methods

A total of 18 in vitro tests were undertaken ex vivo to compare drug-specific proliferation and cytokine release (interferon-? [IFN-?] and interleukin-4 [IL-4]). The study included 16 patients with DHR: 7 children tested in the acute phase, 7 tested after recovery, and 2 tested during both the acute and postrecovery phases.

Results

The sensitivity of the LPA was better during the acute stage of DHR in children. Cytokine assays revealed a higher frequency of positive drug-specific responses compared with LPA in both the acute (LPA, 77.8%; IFN-?, 88.9%; IL-4, 100%) and postrecovery phases (LPA, 33.3%; IFN-?, 66.7%; IL-4, 66.7%). Combination cytokine assays (IFN-? and IL-4) produced higher positive drug-specific responses in identifying culprit drugs compared with LPA in both the acute and postrecovery phases.

Conclusions

In vitro drug-induced T-cell proliferation and cytokine release assays are useful for identification of the causative drug in children with DHR. Cytokine assays (IFN-? and IL-4) were better than LPA, but when combined, they offer even greater utility in the diagnosis of acute and postrecovery DHR. Cytokine detection is rapid and does not involve radioactivity. These novel in vitro assays may offer a significant advancement in our future management of DHR in children.

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Identifiers

ORCID for Michael Ardern-Jones: orcid.org/0000-0003-1466-2016

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