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Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2018-03-05 , DOI: 10.1016/j.jaci.2018.01.044
M Cecilia Berin 1 , Alexander Grishin 1 , Madhan Masilamani 1 , Donald Y M Leung 2 , Scott H Sicherer 1 , Stacie M Jones 3 , A Wesley Burks 4 , Alice K Henning 5 , Peter Dawson 5 , Joanna Grabowska 1 , Charuta Agashe 1 , Wendy F Davidson 6 , Robert A Wood 7 , Hugh A Sampson 1
Affiliation  

Background

Egg allergy is phenotypically heterogeneous. A subset of patients with egg allergy can tolerate egg in an extensively heated form. Inclusion of baked egg (BE) into the diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown.

Objectives

We sought to study egg-specific antibody, basophil, and T-cell responses in children with reactivity or tolerance to BE.

Methods

All participants underwent double-blind, placebo-controlled challenges to BE, and those who tolerated BE were challenged with unheated egg white protein to confirm clinical egg reactivity. Laboratory studies included serum antibody measurements, basophil activation tests, and CD154-based detection of egg-responsive T cells by using flow cytometry.

Results

Of the 129 children studied, BE-reactive participants had significantly greater levels of egg-, ovalbumin-, and ovomucoid-specific IgE; lower ratios of egg-specific IgG4/IgE; and increased basophil activation in response to egg. Among all participants, CD154-based profiling revealed egg-responsive T cells producing IL-4 and IL-13 but little IL-10 or IFN-γ, as well as the presence of egg-responsive Foxp3+CD25+CD127low regulatory T cells. Egg-responsive T cells expressed CCR4, CCR6, and CXCR5, indicating capacity for homing to the skin, mucosa, and B-cell follicles. However, neither the frequency nor phenotype of egg-responsive T cells was different in those with tolerance or reactivity to BE.

Conclusions

Egg-specific antibody and basophil responses, but not T-cell responses, are greater in those with reactivity versus tolerance to BE. Egg-specific antibody and T-cell responses were highly heterogeneous in this cohort. The clinical implications of this immune heterogeneity will need to be studied longitudinally.



中文翻译:


鸡蛋特异性 IgE 和嗜碱性粒细胞激活与临床鸡蛋过敏表型相关,但鸡蛋特异性 T 细胞计数不相关


 背景


鸡蛋过敏具有不同的表型。一部分鸡蛋过敏患者可以耐受高度加热的鸡蛋。在饮食中加入烤鸡蛋 (BE) 可加速鸡蛋过敏的解决。相反,BE 反应性与持续性疾病相关。这种临床异质性的免疫基础尚不清楚。

 目标


我们试图研究对 BE 有反应性或耐受性的儿童的卵特异性抗体、嗜碱性粒细胞和 T 细胞反应。

 方法


所有参与者都接受了双盲、安慰剂对照的 BE 挑战,那些耐受 BE 的参与者接受了未加热的蛋清蛋白的挑战,以确认临床鸡蛋反应性。实验室研究包括血清抗体测量、嗜碱性粒细胞活化测试以及使用流式细胞术对卵反应性 T 细胞进行基于 CD154 的检测。

 结果


在研究的 129 名儿童中,BE 反应性参与者的卵子、卵清蛋白和卵类粘蛋白特异性 IgE 水平显着更高;鸡蛋特异性 IgG 4 /IgE 的比率较低;并增加对鸡蛋的反应的嗜碱性粒细胞活化。在所有参与者中,基于 CD154 的分析显示卵反应性 T 细胞产生 IL-4 和 IL-13,但很少产生 IL-10 或 IFN-γ,并且存在卵反应性 Foxp3 + CD25 + CD127调节 T 细胞。卵反应性 T 细胞表达 CCR4、CCR6 和 CXCR5,表明具有归巢至皮肤、粘膜和 B 细胞滤泡的能力。然而,在那些对BE具有耐受性或反应性的细胞中,卵反应性T细胞的频率和表型都没有不同。

 结论


对 BE 具有反应性和耐受性的个体中,卵特异性抗体和嗜碱性粒细胞反应更强,但 T 细胞反应则不然。该队列中的卵特异性抗体和 T 细胞反应具有高度异质性。这种免疫异质性的临床影响需要纵向研究。

更新日期:2018-03-05
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