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A double-blind placebo-controlled birch allergy vaccination study II: correlation between inhibition of IgE binding, histamine release and facilitated allergen presentation.

机译:双盲安慰剂控制的桦木过敏疫苗接种研究II:抑制IgE结合,组胺释放和促进过敏原呈递之间的相关性。

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BACKGROUND: The pathogenesis of IgE-mediated allergic disease is closely related to the production of T-helper type 2 (Th2) cytokines, which lead to IgE production pivotal for activation of mast cells and basophils. Proliferating T cells along with eosinophils expanded and attracted by Th2 cytokines are major contributors to the late-phase reaction. The activation of these Th2 cells is strongly enhanced by CD23-mediated IgE facilitated allergen presentation (FAP). OBJECTIVE: The present study aims to investigate the effect of specific immunotherapy (SIT)-induced allergen-specific non-IgE antibodies (blocking antibodies) on IgE binding to allergen, histamine release (HR) and CD23-mediated allergen uptake in antigen-presenting cells. METHODS: Competition between IgE and non-IgE for allergen binding was studied by Advia Centaur antibody measurements, passively sensitized basophils were used to study HR and IgE-facilitated binding of allergen to B cells (FAP) was studied by flow cytometry. FAP measurements were performed both with and without the addition of a reference IgE serum, which was included to obtain optimal complex formation. The serum samples were obtained from birch pollen immunotherapy (n=21) or placebo control patients (n=21) before and after 1 and 2 years of treatment. RESULTS: Statistically significant reduction of all parameters investigated was observed after 1 year of treatment and the effect was maintained during the second year of treatment. There was a clear correlation between the two FAP measurements and between each of them and the level of T cell activation reported upon previously. Moreover, strong correlations were found between changes in FAP, IgE binding and HR. CONCLUSION: The present study clearly demonstrates that SIT induces changes in the composition of serum antibodies that inhibit IgE binding, HR and FAP to a similar extent. This suggests that these measurements, individually or in combination, may be used to monitor the immunological effect of SIT, even though direct correlations to changes in clinical parameters could not be demonstrated.
机译:背景:IgE介导的过敏性疾病的发病机制与T杆辅助2(TH2)细胞因子的产生密切相关,这导致IgE产生枢转用于激活肥大细胞和嗜碱性粒细胞。增殖T细胞与嗜酸性粒细胞膨胀并吸引到Th2细胞因子上是后期反应的主要贡献者。 CD23介导的IgE促进过敏原呈递(FAP)强大地增强了这些TH2细胞的活化。目的:目前的研究旨在探讨特定免疫疗法(SIT) - 诱导的过敏原特异性非IgE抗体(阻断抗体)对IgE结合,组胺释放(HR)和CD23介导的过敏原吸收剂在抗原呈递中的效果细胞。方法:通过Advia Centaur抗体测量研究了IgE和非IgE之间的竞争,通过流式细胞术研究了被动敏化的嗜碱性粒细胞,通过流式细胞术研究了HR和IgE促进过敏原与B细胞(FAP)的结合。在没有添加参考IgU血清的情况下进行FAP测量,以获得最佳的复杂形成。在1至2年后,从桦树花粉免疫疗法(N = 21)或安慰剂对照患者(N = 21)获得血清样品。结果:在治疗1年后观察到所研究的所有参数的统计学显着降低,疗效在治疗后的第二年维持。两个FAP测量和它们中的每一个之间存在明显的相关性和先前报告的T细胞激活的水平。此外,在FAP,IgE结合和HR的变化之间发现了强相关的相关性。结论:本研究清楚地证明,静置诱导血清抗体组合物的变化,其抑制IgE结合,HR和FAP在类似的程度上。这表明这些测量,单独或组合可用于监测静坐的免疫效果,即使无法证明与临床参数的变化的直接相关性。

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