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

In vitro rapid diagnostic tests for severe drug hypersensitivity reactions in children
In vitro rapid diagnostic tests for severe drug hypersensitivity reactions in children
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.
61-66
Haw, Wei Yann
7a4db90c-779e-41d6-9b62-236159e6c463
Polak, Marta
e0ac5e1a-7074-4776-ba23-490bd4da612d
Mcguire, Carolann
890ed1cc-eb1a-46d5-9702-213d6aaa0b37
Erlewyn-Lajeunesse, Michel
cce68767-8d78-45ad-bb00-3da4f83d4ea6
Ardern-Jones, Michael
7ac43c24-94ab-4d19-ba69-afaa546bec90
Haw, Wei Yann
7a4db90c-779e-41d6-9b62-236159e6c463
Polak, Marta
e0ac5e1a-7074-4776-ba23-490bd4da612d
Mcguire, Carolann
890ed1cc-eb1a-46d5-9702-213d6aaa0b37
Erlewyn-Lajeunesse, Michel
cce68767-8d78-45ad-bb00-3da4f83d4ea6
Ardern-Jones, Michael
7ac43c24-94ab-4d19-ba69-afaa546bec90

Haw, Wei Yann, Polak, Marta, Mcguire, Carolann, Erlewyn-Lajeunesse, Michel and Ardern-Jones, Michael (2016) In vitro rapid diagnostic tests for severe drug hypersensitivity reactions in children. Annals of Allergy, Asthma and Immunology, 117 (1), 61-66. (doi:10.1016/j.anai.2016.04.017). (PMID:27221062)

Record type: Article

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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More information

Accepted/In Press date: 4 April 2016
e-pub ahead of print date: 21 May 2016
Published date: July 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 395341
URI: https://eprints.soton.ac.uk/id/eprint/395341
PURE UUID: f2657451-fceb-4924-bd8d-725ae0719980

Catalogue record

Date deposited: 25 May 2016 13:15
Last modified: 03 Dec 2019 06:42

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