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

Mast cell activation test in the diagnosis of allergic disease and anaphylaxis.
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DOI:
10.1016/j.jaci.2018.01.043
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发表时间:
2018-08
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
通讯作者:
Bulfone-Paus S
Bulfone-Paus S
中科院分区:
其他
文献类型:
--
作者:
Bahri R;Custovic A;Korosec P;Tsoumani M;Barron M;Wu J;Sayers R;Weimann A;Ruiz-Garcia M;Patel N;Robb A;Shamji MH;Fontanella S;Silar M;Mills ENC;Simpson A;Turner PJ;Bulfone-Paus S

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食物过敏是一个日益严重的公共卫生问题,也是危及生命的过敏反应的最常见原因。传统的过敏试验评估过敏原特异性IgE的存在,显著高估了真正的临床过敏率,导致过度诊断和对健康相关生活质量的不良影响。为了对一种新的诊断工具进行初步验证和评估,我们使用了肥大细胞活化试验(MAT)。原代人血来源的肥大细胞(MCs)是从外周血前体中产生的,用患者血清致敏,然后与过敏原孵育。通过流式细胞术和介质释放评估MC脱粒。我们比较了MAT与现有诊断工具的诊断性能,以评估一组接受双盲、安慰剂对照激发的花生致敏受试者。根据表面活化标志物(CD 63和CD 107 a)的表达和功能测定(前列腺素D2和β-氨基己糖苷酶释放),用花生、草花粉和Hyplittera(黄蜂毒液)过敏患者血清致敏的人血来源MC显示出过敏原特异性和剂量依赖性脱粒。在这组花生致敏受试者中,发现MAT与其他测试模式(包括成分分辨诊断和嗜碱性粒细胞活化测试)相比具有上级辨别性能。使用功能性主成分分析,我们在所得剂量-反应曲线中确定了5个反应性簇或模式,初步分析时,这些簇或模式对应于攻毒时观察到的反应表型。MAT是一个强大的工具,可以提供上级诊断性能相比,现有的过敏诊断,并可能是有用的,以探索在过敏反应中嗜碱性粒细胞和MC之间的效应细胞功能的差异。
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. To undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT). 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. 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. 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.
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