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接受双盲安慰剂对照食物激发试验系列的学童细胞因子mRNA表达和粪便生物标志物的动态变化

Dynamics of cytokine mRNA expression and fecal biomarkers in school-children undergoing a double-blind placebo-controlled food challenge series.

作者信息

Winberg Anna, Nagaeva Olga, Nagaev Ivan, Lundell Catarina, Arencibia Ignacio, Mincheva-Nilsson Lucia, Rönmark Eva, West Christina E

机构信息

Department of Clinical Sciences, Pediatrics, Umeå University, Sweden.

Department of Clinical Microbiology, Clinical Immunology, Umeå University, Sweden.

出版信息

Cytokine. 2016 Dec;88:259-266. doi: 10.1016/j.cyto.2016.09.014. Epub 2016 Oct 1.

DOI:10.1016/j.cyto.2016.09.014
PMID:27697703
Abstract

BACKGROUND

There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming.

OBJECTIVE

To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included.

METHODS

Twelve-year-old children from a population-based cohort reporting complete avoidance of milk, egg, cod or wheat due to perceived hypersensitivity were clinically examined and those with suspected food allergy were evaluated with a 3-session double-blind placebo-controlled food challenge (n=18). Seven healthy controls participated in a double-blind challenge with egg. Before and after the challenge series, the cytokine mRNA expression was quantified for 13 cytokines discriminating between humoral Th2-, cytotoxic Th1-, regulatory Th3/Tr1- and inflammatory responses. Fecal calprotectin and eosinophil-derived neurotoxin (EDN) were also analyzed in children with suspected food allergy before and after the challenge series.

RESULTS

Pre challenge, children with suspected food allergy had higher IL-13andTNF-α expression and lower IFN-γ and IL-15 expression compared to healthy controls (all p<0.05). Children with challenge-proven food allergy had increased IL13andIL-10 expression compared to the levels seen in negative challenges (p<0.05). Post challenge, IL-1β and IL-6 mRNA levels were elevated in the food allergic children compared to controls (p<0.05). Fecal calprotectin and EDN levels were higher in challenge-proven food allergy compared to a negative challenge although not statistically significantly.

CONCLUSION & CLINICAL RELEVANCE: Increased baseline mRNA levels of the Th2-related cytokine IL-13 and the regulatory cytokine IL-10 predicted a positive food challenge outcome. These cytokines in combination with fecal calprotectin and EDN might serve as future prognostic markers for symptomatic, IgE-mediated food allergy but need further validation in a larger patient cohort.

摘要

背景

由于目前的诊断方法不足和/或耗时费力,因此需要针对症状性食物过敏的预后标志物。

目的

评估疑似对牛奶、鸡蛋或鳕鱼过敏的学龄儿童以及健康对照在双盲安慰剂对照食物激发试验系列前后外周血单核细胞(PBMC)中的细胞因子mRNA谱。纳入激发试验前后粪便炎症生物标志物的分析。

方法

从一个基于人群的队列中选取12岁儿童,这些儿童因感觉过敏而报告完全避免食用牛奶、鸡蛋、鳕鱼或小麦,对他们进行临床检查,并对疑似食物过敏的儿童进行为期3个阶段的双盲安慰剂对照食物激发试验(n = 18)。7名健康对照参与了鸡蛋的双盲激发试验。在激发试验系列前后,对区分体液Th2、细胞毒性Th1、调节性Th3/Tr1和炎症反应的13种细胞因子的mRNA表达进行定量。还对疑似食物过敏儿童在激发试验系列前后的粪便钙卫蛋白和嗜酸性粒细胞衍生神经毒素(EDN)进行了分析。

结果

激发试验前,与健康对照相比,疑似食物过敏儿童的IL-13和TNF-α表达较高,而IFN-γ和IL-15表达较低(均p<0.05)。与阴性激发试验相比,激发试验证实食物过敏的儿童IL-13和IL-10表达增加(p<0.05)。激发试验后,与对照相比,食物过敏儿童的IL-1β和IL-6 mRNA水平升高(p<0.05)。与阴性激发试验相比,激发试验证实食物过敏的粪便钙卫蛋白和EDN水平更高,尽管无统计学意义。

结论及临床意义

Th2相关细胞因子IL-13和调节性细胞因子IL-10的基线mRNA水平升高预示食物激发试验结果为阳性。这些细胞因子与粪便钙卫蛋白和EDN联合可能作为症状性IgE介导食物过敏的未来预后标志物,但需要在更大的患者队列中进一步验证。

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