Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes
Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes
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DOI：
10.1016/j.jaci.2016.12.940
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发表时间：
2017-02-01
影响因子：
14.2
通讯作者：
Xu, Cheng-Jian
中科院分区：
文献类型：
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作者：
Anto, Josep M.;Bousquet, Jean;Xu, Cheng-Jian
哮喘、鼻炎和湿疹是多种遗传和环境因素通过IgE相关和非IgE相关机制相互关联的复杂疾病。过敏性疾病发展的机制（MeDALL; EU FP 7-CP-IP;项目编号：261357; 2010-2015）通过将流行病学、临床和机制研究（包括体内和体外模型）联系起来，研究了过敏性疾病在临床和机制水平上的复杂联系。MeDALL整合了14个欧洲出生队列，包括44，010名参与者和160名怀孕至20岁之间的队列随访。使用新标准化的MeDALL核心问卷对13000名儿童进行了青春期后的前瞻性随访。为3，292名儿童开发的IgE敏感性增加的过敏原分子微阵列。以前的研究估计有10 000名儿童接触空气污染。组学数据包括来自历史全基因组关联研究（23，000名儿童）和DNA甲基化（2，173），靶向多重生物标志物（1，427）和转录组学（723）研究的数据。在16，147名4岁儿童和11，080名8岁儿童中使用经典流行病学和机器学习方法，MeDALL显示湿疹，鼻炎和哮喘的多发病率，估计只有38%的多发病率可归因于IgE致敏。MeDALL提出了一种新的观点，即多药不依赖于IgE致敏，并表明单致敏和多致敏代表2种不同的表型。MeDALL的翻译组分通过鉴定一种新的过敏性表型来显示，其特征在于多敏性和多突变性，其与过敏性症状的频率、持续性和严重性相关。MeDALL的结果将有助于整合过敏性疾病的个性化，预测性，预防性和参与性方法。
Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgEassociated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.