在生命的头 7 年里，在 6 个月大时接触细菌的外周血单个核细胞产生的白细胞介素-2（IL-2）反应减少与总 IgE 升高和过敏性鼻炎有关。
Reduced IL-2 response from peripheral blood mononuclear cells exposed to bacteria at 6 months of age is associated with elevated total-IgE and allergic rhinitis during the first 7 years of life.
机构信息
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark; Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
出版信息
EBioMedicine. 2019 May;43:587-593. doi: 10.1016/j.ebiom.2019.04.047. Epub 2019 May 2.
BACKGROUND
Autoimmunity and allergy have been associated with decreased number and function of regulatory T-cells (Tregs) and low interleukin-2 (IL-2) levels. We aimed to investigate if the release of IL-2 from peripheral blood mononuclear cells (PBMCs) stimulated with pathogenic airway bacteria was associated with development of allergy-outcomes in early childhood.
METHODS
PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC) mother-child cohort, and subsequently stimulated with H. influenzae, M. catarrhalis and S. pneumoniae in in vitro cultures. Levels of cytokines (IL-2, IL-10, IFN-γ, TNF-α, IL-5, IL-13 and IL-17A) were determined in the supernatant by electrochemiluminescence immunoassays. The immune profiles were analyzed for association with development of total-IgE, allergic sensitization and rhinitis during the first 7 years of life using regression models and principal component analysis (PCA).
FINDINGS
An attenuated IL-2 response to stimulation with H. influenzae (p = 0∙011) and M. catarrhalis (p = 0∙027) was associated with elevated total-IgE at age 7, which was confirmed in a multivariate PCA model including all cytokine measurements (PC2, p = 0∙032). An immune profile with both reduced IL-2 and elevated IL-5 was associated with increased risk of allergic rhinitis (PC3, p = 0∙038). We found no associations with development of allergic sensitization.
INTERPRETATION
A reduced IL-2 response from PBMCs exposed to common pathogenic airway bacteria at age 6 months was associated with elevated total-IgE and allergic rhinitis during the first 7 years of life. These findings suggest that suppressed Treg activity in early life may herald onset of allergy in early childhood, which could be a target for low-dose IL-2 trials in the future. FUND: COPSAC is funded by private and public research funds all listed on www.copsac.com.
背景
自身免疫和过敏与调节性 T 细胞（Tregs）数量和功能减少以及白细胞介素-2（IL-2）水平降低有关。我们旨在研究外周血单个核细胞（PBMCs）在受到致病性气道细菌刺激后释放 IL-2 是否与儿童早期过敏结局的发展有关。
方法
在来自哥本哈根儿童哮喘前瞻性研究 2000（COPSAC）母子队列的 331 名婴儿中，于 6 月龄时分离 PBMCs，随后在体外培养中用流感嗜血杆菌、卡他莫拉菌和肺炎链球菌刺激。通过电化学发光免疫分析法测定上清液中细胞因子（IL-2、IL-10、IFN-γ、TNF-α、IL-5、IL-13 和 IL-17A）的水平。使用回归模型和主成分分析（PCA）分析免疫谱与生命最初 7 年内总 IgE、过敏致敏和鼻炎的发展之间的关系。
结果
流感嗜血杆菌（p=0.011）和卡他莫拉菌（p=0.027）刺激后 IL-2 反应减弱与 7 岁时总 IgE 升高有关，这在包括所有细胞因子测量的多元 PCA 模型中得到了证实（PC2，p=0.032）。同时存在 IL-2 降低和 IL-5 升高的免疫谱与过敏性鼻炎的风险增加相关（PC3，p=0.038）。我们未发现与过敏致敏发展相关的关联。
结论
6 月龄时暴露于常见致病性气道细菌的 PBMCs 中 IL-2 反应减弱与生命最初 7 年内总 IgE 和过敏性鼻炎有关。这些发现表明，生命早期 Treg 活性受抑制可能预示着儿童早期过敏的发生，这可能是未来低剂量 IL-2 试验的靶点。
资金
COPSAC 由私人和公共研究基金资助，详情请访问 www.copsac.com。
Zotero 插件