• Rajia Bahri, Adnan Custovic, Peter Korosec, Marina Tsoumani, Martin Barron, Jiakai Wu, Rebekah Sayers, Alf Weimann, Monica Ruiz-Garcia, Nandinee Patel, Abigail Robb, Mohamed H Shamji, Sara Fontanella, Mira Silar, Mills E N Clare ENC Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, and NIHR Manchester Biomedical Rese, Angela Simpson, Paul J Turner, and Silvia Bulfone-Paus.
• Division of Musculoskeletal and Dermatological Sciences & Manchester Collaborative Centre for Inflammation Research (MCCIR), School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
• J. Allergy Clin. Immunol. 2018 Aug 1; 142 (2): 485-496.e16.

BackgroundFood 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.ObjectiveTo undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT).MethodsPrimary 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.ResultsHuman 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.ConclusionThe 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.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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