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Heterogeneous responses and cross reactivity between the major peanut allergens Ara h 1, 2,3 and 6 in a mouse model for peanut allergy

机译:花生过敏小鼠模型中主要花生过敏原ara h 1,2,3和6的异质反应和交叉反应

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摘要

BACKGROUND: The relative contribution and the relation between individual peanut allergens in peanut allergic responses is still matter of debate. We determined the individual contribution of peanut proteins to B, T cell and allergic effector responses in a mouse model for peanut allergy. METHODS: Mice were immunized and challenged by oral gavage with peanut protein extract or isolated allergens Ara h 1, 2, 3 and 6 followed by assessment of food allergic manifestations. In addition, T cell responses to the individual proteins were measured by an in vitro dendritic cell-T cell assay. RESULTS: Sensitization with the individual peanut proteins elicited IgE responses with specificity to the allergen used as expected. However, cross reactivity among Ara h 1, 2, 3 and 6 was observed. T cell re-stimulations with peanut extract and individual peanut proteins also showed cross reactivity between Ara h 1, 2, 3 and 6. Despite the cross reactivity at the IgE level, only Ara h 2 and 6 were able to elicit mast cell degranulation after an oral challenge. However, after systemic challenge, Ara h 1, 2 and 6 and to lesser extent Ara h 3 were able to elicit anaphylactic responses. CONCLUSIONS: Ara h 1, 2, 3 and 6 sensitize via the intra-gastric route, but differ in their capacity to cause allergic effector responses. Interestingly, extensive cross reactivity at T cell and antibody level is observed among Ara h 1, 2, 3 and 6, which may have important implications for the diagnosis and therapy of peanut allergy. Awareness about the relative contribution of individual peanut allergens and cross reactivity between these allergens is of importance for current research in diagnostics and therapeutics for and the mechanism of peanut allergy.
机译:背景:花生过敏反应中花生过敏原的相对贡献和相互关系仍是争论的焦点。我们确定了花生蛋白对花生过敏的小鼠模型中B,T细胞和过敏效应反应的个体贡献。方法:用花生蛋白提取物或分离的过敏原Ara h 1、2、3和6进行口服管饲法对小鼠进行免疫和攻击,然后评估食物的过敏表现。另外,通过体外树突细胞-T细胞测定法测量了对单个蛋白质的T细胞应答。结果:单个花生蛋白的敏化引起对预期使用的过敏原具有特异性的IgE反应。但是,观察到Ara h 1、2、3和6之间有交叉反应。用花生提取物和单个花生蛋白进行的T细胞再刺激也显示出Ara h 1、2、3和6之间的交叉反应性。尽管在IgE水平上具有交叉反应性,但是只有Ara h 2和6能够在肥大细胞脱粒后引起肥大细胞脱粒。口头挑战。然而,在全身性攻击后,Ara h 1、2和6以及较小程度的Ara h 3能够引起过敏反应。结论:Ara h 1、2、3和6通过胃内途径致敏,但它们引起过敏效应反应的能力不同。有趣的是,在Ara h 1、2、3和6之间观察到在T细胞和抗体水平上广泛的交叉反应性,这可能对花生过敏的诊断和治疗具有重要意义。认识到各个花生过敏原的相对贡献以及这些过敏原之间的交叉反应性对于当前花生过敏的诊断和治疗研究及其机理至关重要。

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