Kinetics, cross-reactivity, and specificity of Bet v 1-specific IgG4 antibodies induced by immunotherapy with birch pollen
Kinetics, cross-reactivity, and specificity of Bet v 1-specific IgG4 antibodies induced by immunotherapy with birch pollen
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DOI：
10.1111/all.12236
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发表时间：
2013-11-01
期刊：
影响因子：
12.4
通讯作者：
Bohle, B.
中科院分区：
文献类型：
--
作者：
Subbarayal, B.;Schiller, D.;Bohle, B.
背景桦树花粉过敏原特异性IgE抗体经常与Bet v 1同源食物蛋白发生交叉反应，如榛子中的Cor a 1和苹果中的Mal d 1。用桦树花粉（BP-SIT）的特异性免疫疗法诱导抑制IgE与Betv 1结合的IgG 4抗体。然而，关于BP-SIT诱导的Bet v 1特异性IgG 4抗体与食物过敏原的交叉反应性的信息有限。在这项研究中，我们调查的动力学的生产，交叉反应，和IgE阻断活性的Betv 1特异性IgG 4抗体出现在传统的BP-SIT和IgG 4-表位是否重叠与IgE epitopes.MethodsIgE和IgG 4水平特异性的Betv 1，Mal d 1，和Cor A 1在42桦树花粉过敏患者之前和期间BP-SIT。IgE结合的抑制进行了研究，通过IgE促进抗原结合试验和嗜碱性粒细胞活化试验。此外，评估IgE介导的食物过敏原反应性Bet v 1特异性T细胞系活化的抑制。应用噬菌体展示肽的竞争性免疫筛选来选择分别由IgE和IgG 4抗体识别的模拟表位。由此产生的mimotopes映射在表面上的3D结构的过敏原使用基于计算机的algorithm.ResultsBP-SIT显着增加的Bet V 1-和食物过敏原反应性IgG 4抗体。同时，过敏原特异性IgE水平显著下降。含有食物过敏原反应性IgG 4抗体的血清抑制IgE结合、嗜碱性粒细胞活化和IgE介导的食物过敏原诱导的T细胞增殖。预测的IgE和IgG 4抗原表位上的所有过敏原表现出高度的重叠。ConclusionOur结果表明，BP-SIT可能会诱导Bet V 1特异性IgG 4抗体，交叉反应与相关的食物过敏原和抑制IgE结合的表位竞争。
BackgroundIgE antibodies specific for the major birch pollen allergen frequently cross-react with Bet v 1 homologous food proteins, for example Cor a 1 in hazelnut and Mal d 1 in apple. Specific immunotherapy with birch pollen (BP-SIT) induces IgG4 antibodies that inhibit IgE binding to Bet v 1. However, information on cross-reactivity of BP-SIT-induced Bet v 1-specific IgG4 antibodies with food allergens is limited. In this study, we investigated the kinetics of production, cross-reactivity, and IgE-blocking activity of Bet v 1-specific IgG4 antibodies emerging during conventional BP-SIT and whether IgG4-epitopes overlapped with IgE epitopes.MethodsIgE and IgG4 levels specific for Bet v 1, Mal d 1, and Cor a 1 were determined in 42 birch pollen-allergic patients before and during BP-SIT. Inhibition of IgE binding was studied by IgE-facilitated antigen-binding assays and basophil activation tests. Furthermore, inhibition of IgE-mediated activation of food allergen-reactive Bet v 1-specific T-cell lines was assessed. Competitive immunoscreening of phage-displayed peptides was applied to select mimotopes recognized by IgE and IgG4 antibodies, respectively. The resulting mimotopes were mapped on the surface of the 3D structure of the allergens using a computer-based algorithm.ResultsBP-SIT significantly increased Bet v 1- and food allergen-reactive IgG4 antibodies. In parallel, allergen-specific IgE levels decreased significantly. Sera containing food allergen-reactive IgG4 antibodies inhibited IgE binding, basophil activation, and IgE-mediated food allergen-induced T-cell proliferation. Predicted IgE and IgG4 epitopes on all allergens showed high overlap.ConclusionOur results indicate that BP-SIT may induce Bet v 1-specific IgG4 antibodies that cross-react with related food allergens and inhibit IgE binding by epitope competition.