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J Allergy Clin Immunol. 2018 Aug;142(2):485-496.e16. doi: 10.1016/j.jaci.2018.01.043. Epub 2018 Mar 5.

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

Author information

1
Division of Musculoskeletal and Dermatological Sciences & Manchester Collaborative Centre for Inflammation Research (MCCIR), School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
2
Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom.
3
Laboratory for Clinical Immunology & Molecular Genetics, University Hospital for Respiratory and Allergic Diseases, Golnik, Slovenia.
4
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, and NIHR Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
5
EUROIMMUN AG, Lübeck, Germany.
6
Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
7
Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom. Electronic address: p.turner@imperial.ac.uk.
8
Division of Musculoskeletal and Dermatological Sciences & Manchester Collaborative Centre for Inflammation Research (MCCIR), School of Biological Sciences, University of Manchester, Manchester, United Kingdom. Electronic address: silvia.bulfone-paus@manchester.ac.uk.

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.

KEYWORDS:

Anaphylaxis; basophil activation test; diagnosis; food allergy; mast cell activation test; mast cells; peanut allergy

Comment in

PMID:
29518421
PMCID:
PMC6075471
DOI:
10.1016/j.jaci.2018.01.043
[Indexed for MEDLINE]
Free PMC Article

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