急性 FPIES 反应与 IL-17 炎症特征有关。
Acute FPIES reactions are associated with an IL-17 inflammatory signature.
机构信息
Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
出版信息
J Allergy Clin Immunol. 2021 Sep;148(3):895-901.e6. doi: 10.1016/j.jaci.2021.04.012. Epub 2021 Apr 20.
BACKGROUND
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear.
OBJECTIVE
Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood.
METHODS
Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry.
RESULTS
Symptomatic FPIES challenge results were associated with significant elevation of levels of cytokines and chemokines, including IL-17 family markers (IL-17A, IL-22, IL-17C, and CCL20) and T-cell activation (IL-2), and innate inflammatory markers (IL-8, oncostatin M, leukemia inhibitory factor, TNF-α, IL-10, and IL-6). The level of the mucosal damage marker regenerating family member 1 alpha (REG1A) was also significantly increased. These biomarkers were not increased in asymptomatic challenges or IgE-mediated allergy. The level of phospho-STAT3 was significantly elevated in myeloid and T cells after challenge in individuals with symptoms. Mass cytometry indicated preferential activation of nonconventional T-cell populations, including γδ T cells and CD3CD4CD8CD161 cells; however, the potential sources of IL-17 in PBMCs were primarily CD4 T17 cells.
CONCLUSIONS
These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES.
背景
食物蛋白诱导的肠炎综合征（FPIES）是一种非 IgE 介导的食物过敏，其特征是在摄入致病食物后数小时内出现大量呕吐。我们之前曾报道过，FPIES 与系统性固有免疫激活有关，而没有可检测到的抗原特异性抗体或 T 细胞反应。免疫系统对特定食物的识别机制仍不清楚。
目的
通过对外周血进行蛋白质组学和流式细胞术分析，确定 FPIES 反应的免疫机制。
方法
有 FPIES 病史的儿童接受了监督下的口服食物挑战。在基线、症状发作时和症状发作后 4 小时采集血样。我们分析了 23 名儿童（11 名反应者和 12 名过敏消退者）的样本。通过接近连接测定法分析了 184 种蛋白质标记物，并通过多重免疫测定法进行了验证。通过质谱流式细胞术和光谱流式细胞术分析细胞亚群激活情况。
结果
症状性 FPIES 挑战结果与细胞因子和趋化因子水平的显著升高相关，包括 IL-17 家族标志物（IL-17A、IL-22、IL-17C 和 CCL20）和 T 细胞激活（IL-2）以及固有炎症标志物（IL-8、肿瘤坏死因子-α、IL-10 和 IL-6）。黏膜损伤标志物再生家族成员 1 阿尔法（REG1A）的水平也显著升高。这些生物标志物在无症状挑战或 IgE 介导的过敏中没有增加。在有症状的个体中，挑战后髓样细胞和 T 细胞中的磷酸化 STAT3 水平显著升高。质谱流式细胞术表明，非传统 T 细胞群（包括 γδ T 细胞和 CD3CD4CD8CD161 细胞）优先激活；然而，PBMC 中 IL-17 的潜在来源主要是 CD4 T17 细胞。
结论
这些结果表明，FPIES 中存在独特的 IL-17 特征和固有淋巴细胞的激活。
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