Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
National Heart and Lung Institute, Imperial College London, London, UK.
Pediatr Allergy Immunol. 2021 Nov;32(8):1824-1832. doi: 10.1111/pai.13574. Epub 2021 Jun 28.
Chemokines are important mediators in immune cell recruitment, contributing to allergy development. However, extensive studies of chemokines in the circulation in relation to the presence and development of allergic diseases remain scarce. Our aim was to investigate associations of circulating allergy-related chemokines with the development of asthma and sensitization cross-sectionally and longitudinally in a population-based cohort.
The chemokines CCL17, CCL22, CXCL10, CXCL11 and CCL18 were measured in plasma samples from children in the Manchester Asthma and Allergy Study. Samples were available from cord blood at birth (n = 376), age 1 (n = 195) and age 8 (n = 334). Cross-sectional and longitudinal association analyses were performed in relation to asthma and allergic sensitization, as well as allergic phenotype clusters previously derived using machine learning in the same study population.
In children with asthma and/or allergic sensitization, CCL18 levels were consistently elevated at 1 and/or 8 years of ages. In a longitudinal model including information on asthma from 4 time points (5, 8, 11 and 16 years of ages), we observed a significant association between increasing CCL18 levels at age 1 and a higher risk of asthma from early school age to adolescence (OR = 2.9, 95% CI 1.1-7.6, p = .028). We observed similar associations in longitudinal models for allergic sensitization. Asthma later in life was preceded by increased CXCL10 levels after birth and decreased CXCL11 levels at birth.
Elevated CCL18 levels throughout childhood precede the development of asthma and allergic sensitization. The Th1-associated chemokines CXCL10 and CXCL11 also associated with the development of both outcomes, with differential temporal effects.
趋化因子是免疫细胞募集的重要介质，有助于过敏的发展。然而，与过敏疾病的存在和发展相关的循环趋化因子的广泛研究仍然很少。我们的目的是在一个基于人群的队列中，调查与哮喘和过敏发生的相关性的循环过敏相关趋化因子与哮喘和过敏发生的横断面和纵向相关性。
在曼彻斯特哮喘和过敏研究中，对儿童的血浆样本进行趋化因子 CCL17、CCL22、CXCL10、CXCL11 和 CCL18 的测量。样本来自出生时的脐带血（n=376）、1 岁（n=195）和 8 岁（n=334）。在相同的研究人群中，使用机器学习方法对先前得出的过敏表型聚类进行了横断面和纵向关联分析。
在患有哮喘和/或过敏的儿童中，CCL18 水平在 1 岁和/或 8 岁时持续升高。在一个包含来自 4 个时间点（5、8、11 和 16 岁）的哮喘信息的纵向模型中，我们观察到 CCL18 水平在 1 岁时升高与从早期学龄期到青春期的哮喘风险升高之间存在显著相关性（OR=2.9，95%CI 1.1-7.6，p=0.028）。我们在针对过敏的纵向模型中也观察到了类似的关联。在生命后期发生的哮喘之前，出生后 CXCL10 水平升高，出生时 CXCL11 水平降低。
整个儿童时期 CCL18 水平升高先于哮喘和过敏的发生。Th1 相关趋化因子 CXCL10 和 CXCL11 也与这两种结局的发生相关，具有不同的时间效应。
