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Mast cell activation test in the diagnosis of allergic disease and anaphylaxis

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Title: Mast cell activation test in the diagnosis of allergic disease and anaphylaxis
Authors: Bahri, R
Custovic, A
Korosec, P
Tsoumani, M
Barron, M
Wu, J
Sayers, R
Weimann, A
Ruiz Garcia, M
Patel, N
Robb, A
Shamji, M
Fontanella, S
Silar, M
Mills, C
Simpson, A
Turner, PJ
Bulfone-Paus, S
Item Type: Journal Article
Abstract: Background Food allergy is an increasing public health issue and the most common cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy and resulting in overdiagnosis and adverse effect on health-related quality of life. Objective To undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT). Methods Primary human blood-derived mast cells (MCs) were generated from peripheral blood precursors, sensitized with patients' sera, and then incubated with allergen. MC degranulation was assessed by means of flow cytometry and mediator release. We compared the diagnostic performance of MATs with that of existing diagnostic tools to assess in a cohort of peanut-sensitized subjects undergoing double-blind, placebo-controlled challenge. Results Human blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose-dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D2 and β-hexosaminidase release). In this cohort of peanut-sensitized subjects, the MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests. Using functional principle component analysis, we identified 5 clusters or patterns of reactivity in the resulting dose-response curves, which at preliminary analysis corresponded to the reaction phenotypes seen at challenge. Conclusion The MAT is a robust tool that can confer superior diagnostic performance compared with existing allergy diagnostics and might be useful to explore differences in effector cell function between basophils and MCs during allergic reactions.
Issue Date: 1-Aug-2018
Date of Acceptance: 16-Jan-2018
URI: http://hdl.handle.net/10044/1/56335
DOI: https://dx.doi.org/10.1016/j.jaci.2018.01.043
ISSN: 0091-6749
Publisher: Elsevier
Start Page: 485
End Page: 496.e16
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 142
Issue: 2
Copyright Statement: © 2018 The Authors. Published by Elsevier Inc. Published on behalf of the American Academy of Allergy, Asthma & Immuno logy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Commission of the European Communities
Funder's Grant Number: MR/K010468/1
ICiC funding 2015/16
RDD02
312147
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
Anaphylaxis
basophil activation test
diagnosis
food allergy
mast cells
mast cell activation test
peanut allergy
BASOPHIL ACTIVATION
FOOD ALLERGY
IGE-SENSITIZATION
PEANUT
CHILDREN
PREVALENCE
DEGRANULATION
METAANALYSIS
TOLERANCE
CULTURE
1107 Immunology
Publication Status: Published
Online Publication Date: 2018-03-05
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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