Mast cell activation test in the diagnosis of allergic disease and anaphylaxis - 04/08/18
, Silvia Bulfone-Paus, MD, PhD a, ⁎∗ 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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Anaphylaxis, basophil activation test, diagnosis, food allergy, mast cells, mast cell activation test, peanut allergy
Abbreviations used : AUC, BAT, CD-sens, CRTH2, DBPCFC, FDA, FPC, hMC, ICC, MAT, MC, PBST, PGD2, ROC, sIgE, SPT
Plan
| Supported by the following grants: Medical Research Council (MRC) Confidence-in-Concepts award to the University of Manchester (sub-award to S.B.-P. and P.J.T., reference MC-PC-15038); an MRC Clinician Scientist award funded (reference MR/K010468/1; to P.J.T.); and National Institute for Health Research (NIHR) Clinical Research Facility and Manchester Allergy and Respiratory Thoracic Surgery (ManARTS) Biobank at University Hospital of South Manchester National Health Service (NHS) Foundation Trust, which is supported by the NIHR Manchester Biomedical Research Centre. The clinical challenges were funded through the NIHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London; the European Union’s Seventh Framework Program for research, technological development, and demonstration under grant agreement no. 312147 (Integrated Approaches to Food Allergen and Allergy Risk Management [iFAAM]); and the Slovenian Research Agency (reference J3-6787). R.S. was supported by the UK Biotechnology and Biological Sciences Research Council through a cooperative award in science and engineering with Campden BRI. P.J.T. and A.C. are supported by the Imperial/NIHR Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR, or the Department of Health. |
|
| Disclosure of potential conflict of interest: A. Custovic has received personal fees from Novartis, Regeneron/Sanofi, ALK-Abelló, Bayer, Thermo Fisher, GlaxoSmithKline, and Boehringer Ingelheim. A. Weimann is employed by EUROIMMUN AG. M. H. Shamji has received grants from ALK-Abelló, Regeneron, Merck, ASIT Biotech.sa, and the Immune Tolerance Network and has received personal fees from ASIT Biotech.sa, ALK-Abelló, Allergopharma, and UCB. E. N. C. Mills has received a grant from the UK Biological and Biotechnological Sciences Research Council, DBV Technologies, Reacta Biotech, the Medical Research Council, the European Union, and the UK Food Standards Agency and has patents pending to Reacta Biotech Ltd (PCT/GB2016/051637 and PCT/GB2016/053829). A. Simpson has received grants from the Medical Research Council, the JP Moulton Charitable Foundation, and the National Institute for Health Research and has received personal fees from Thermo Fisher Scientific. P. J. Turner has received grants from the UK Medical Research Council, the National Institute for Health Research, and the European Commission FP7 scheme. S. Bulfone-Paus has received grants from the UK Medical Research Council, GlaxoSmithKline, and Novartis and has received personal fees from EUROIMMUN AG. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 2
P. 485 - août 2018 Retour au numéro
Article précédent
- The 17,18-epoxyeicosatetraenoic acid–G protein–coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques
- Takahiro Nagatake, Yumiko Shiogama, Asuka Inoue, Junichi Kikuta, Tetsuya Honda, Prabha Tiwari, Takayuki Kishi, Atsushi Yanagisawa, Yosuke Isobe, Naomi Matsumoto, Michiko Shimojou, Sakiko Morimoto, Hidehiko Suzuki, So-ichiro Hirata, Pär Steneberg, Helena Edlund, Junken Aoki, Makoto Arita, Hiroshi Kiyono, Yasuhiro Yasutomi, Masaru Ishii, Kenji Kabashima, Jun Kunisawa
- Safety and efficacy of immunotherapy with the recombinant B-cell epitope–based grass pollen vaccine BM32
- Verena Niederberger, Angela Neubauer, Philippe Gevaert, Mihaela Zidarn, Margitta Worm, Werner Aberer, Hans Jørgen Malling, Oliver Pfaar, Ludger Klimek, Wolfgang Pfützner, Johannes Ring, Ulf Darsow, Natalija Novak, Roy Gerth van Wijk, Julia Eckl-Dorna, Margarete Focke-Tejkl, Milena Weber, Hans-Helge Müller, Joachim Klinger, Frank Stolz, Nora Breit, Rainer Henning, Rudolf Valenta
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?