Mast cell activation test in the diagnosis of allergic disease and anaphylaxis
File(s)
Published version
Author(s)
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.
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.
Date Issued
2018-08-01
Date Acceptance
2018-01-16
Citation
Journal of Allergy and Clinical Immunology, 2018, 142 (2), pp.485-496.e16
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/).
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
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Commission of the European Communities
Grant Number
MR/K010468/1
ICiC funding 2015/16
RDD02
312147
Subjects
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
Date Publish Online
2018-03-05