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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:142

Article

Bahri, Rajia^1,2  Custovic, Adnan³  Korosec, Peter⁵  Tsoumani, Marina^6,7  Barron, Martin^1,2  Wu, Jiakai^1,2  Sayers, Rebekah^6,7  Weimann, Alf⁸  Ruiz-Garcia, Monica³  Patel, Nandinee³  Robb, Abigail^6,7  Shamji, Mohamed H.⁴  Fontanella, Sara³  Silar, Mira⁵  Mills, E. N. Clare^6,7  Simpson, Angela^6,7  Turner, Paul J.³  Bulfone-Paus, Silvia^1,2 

[1] Univ Manchester, Sch Biol Sci, Div Musculoskeletal & Dermatol Sci, Manchester, Lancs, England

[2] Univ Manchester, Sch Biol Sci, MCCIR, Manchester, Lancs, England

[3] Imperial Coll London, Dept Med, Paediat Sect, London, England

[4] Imperial Coll London, Natl Heart & Lung Inst, Sect Allergy & Clin Immunol, London, England

[5] Univ Hosp Resp & Allerg Dis, Lab Clin Immunol & Mol Genet, Golnik, Slovenia

[6] Univ Manchester, Sch Biol Sci, Div Infect Immun & Resp Med, Manchester, Lancs, England

[7] Cent Manchester Univ Hosp NHS Fdn Trust, NIHR Manchester Biomed Res Ctr, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[8] EUROIMMUN AG, Lubeck, Germany

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

DOI  :  10.1016/j.jaci.2018.01.043

来源: Elsevier

【 摘 要 】

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 D-2 and beta-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.

【 授权许可】

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