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介导体介导的食物过敏反应与口腔上皮重塑有关。

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling.

机构信息

Instituto de Medicina Molecular Aplicada, Grupo Hospital de Madrid, Universidad San Pablo-CEU, Madrid, Spain.

Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, Madrid, Spain.

出版信息

J Allergy Clin Immunol. 2019 Feb;143(2):681-690.e1. doi: 10.1016/j.jaci.2018.03.013. Epub 2018 Apr 27.

Abstract

BACKGROUND

In areas of high exposure to grass pollen, allergic patients are frequently sensitized to profilin, and some experience severe profilin-mediated food-induced reactions. This specific population of patients is ideal to study the relationship between respiratory and food allergies.

OBJECTIVE

We sought to determine the role of oral mucosal epithelial barrier integrity in profilin-mediated allergic reactions.

METHODS

Thirty-eight patients with profilin allergy stratified into mild or severe according to their clinical history and response to a profilin challenge test and 6 nonallergic subjects were recruited. Oral mucosal biopsies were used for measurement of CD11c, CD3, CD4, tryptase, claudin-1, occludin, E-cadherin, and vascular endothelial growth factor A levels; Masson trichrome staining; and POSTN, IL33, TPSAB, TPSB, and CMA gene expression analysis by using quantitative RT-PCR. Blood samples were used for basophil activation tests.

RESULTS

Distinct features of the group with severe allergy included the following: (1) impaired epithelial integrity with reduced expression of claudin-1, occludin, and E-cadherin and decreased numbers of epithelial cells, which is indicative of acanthosis, higher collagen deposition, and angiogenesis; (2) inflammatory immune response in the mucosa, with an increased number of CD11c and CD4 infiltrates and increased expression of the cytokine genes POSTN and IL33; and (3) a 10-fold increased sensitivity of basophils to profilin.

CONCLUSIONS

Patients with profilin allergy present with significant damage to the oral mucosal epithelial barrier, which might allow profilin penetration into the oral mucosa and induction of local inflammation. Additionally, severely allergic patients presented with increased sensitivity of effector cells.

摘要

背景

在高暴露于草花粉的地区,过敏患者经常对丝氨酸蛋白酶抑制剂致敏,有些患者会经历严重的丝氨酸蛋白酶抑制剂介导的食物诱导反应。这些特定的患者群体非常适合研究呼吸道和食物过敏之间的关系。

目的

我们旨在确定口腔黏膜上皮屏障完整性在丝氨酸蛋白酶抑制剂介导的过敏反应中的作用。

方法

根据临床病史和对丝氨酸蛋白酶抑制剂挑战试验的反应,将 38 名丝氨酸蛋白酶抑制剂过敏患者分为轻度或重度,并招募了 6 名非过敏受试者。使用口腔黏膜活检测量 CD11c、CD3、CD4、类胰蛋白酶、Claudin-1、occludin、E-cadherin 和血管内皮生长因子 A 的水平;Masson 三色染色;通过定量 RT-PCR 分析 POSTN、IL33、TPSAB、TPSB 和 CMA 基因表达。使用血液样本进行嗜碱性粒细胞活化试验。

结果

严重过敏组的特征包括以下几个方面:(1)上皮完整性受损,Claudin-1、occludin 和 E-cadherin 的表达减少,上皮细胞数量减少,表明棘皮症、胶原沉积增加和血管生成;(2)黏膜中的炎症免疫反应,CD11c 和 CD4 浸润增加,POSTN 和 IL33 等细胞因子基因表达增加;(3)嗜碱性粒细胞对丝氨酸蛋白酶抑制剂的敏感性增加了 10 倍。

结论

丝氨酸蛋白酶抑制剂过敏患者的口腔黏膜上皮屏障存在明显损伤,这可能使丝氨酸蛋白酶抑制剂穿透口腔黏膜并诱导局部炎症。此外,严重过敏患者的效应细胞敏感性增加。

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