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儿童哮喘在学龄期表现出婴儿期对致病性气道细菌异常的免疫反应。

Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants.

机构信息

Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark; Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen, Copenhagen University Hospital, Gentofte, Denmark.

Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.

出版信息

J Allergy Clin Immunol. 2014 Apr;133(4):1008-13. doi: 10.1016/j.jaci.2014.01.010. Epub 2014 Mar 4.

Abstract

BACKGROUND

Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonization of neonatal airways with the pathogenic bacterial strains Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy.

OBJECTIVE

We aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years.

METHODS

The Copenhagen Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response was assessed based on the pattern of cytokines produced and T-cell activation.

RESULTS

The immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17 (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition.

CONCLUSIONS

Children with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic bacteria colonizing the airways in early life might lead to chronic airway inflammation and childhood asthma.

摘要

背景

哮喘是一种高发的慢性肺部疾病,通常起源于儿童早期。新生儿气道定植的致病细菌流感嗜血杆菌、卡他莫拉菌和肺炎链球菌与儿童后期哮喘风险增加有关。我们假设哮喘儿童在婴儿期对致病细菌有异常的免疫反应。

目的

我们旨在评估无症状婴儿的细菌免疫反应,并通过 7 岁时的年龄评估其与后期哮喘发展的关联。

方法

哥本哈根儿童哮喘前瞻性研究队列进行前瞻性随访,7 岁时诊断为哮喘。使用 6 个月龄时分离和储存的 PBMC 分析 292 名婴儿对 H 流感、M 卡他和 S 肺炎球菌的免疫反应。根据产生的细胞因子模式和 T 细胞激活来评估免疫反应。

结果

7 岁时有哮喘的婴儿的细菌免疫反应不同(P =.0007)。特别是,前瞻性哮喘患者的 IL-5(P =.008)、IL-13(P =.057)、IL-17(P =.001)和 IL-10(P =.028)产生异常,而 T 细胞激活或外周 T 细胞组成没有差异。

结论

学龄期哮喘儿童在婴儿期对致病细菌表现出异常的免疫反应。我们提出,对定植于早期气道的致病细菌的异常免疫反应可能导致慢性气道炎症和儿童哮喘。

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