How important is allergic sensitization as a cause of atopic asthma?
How important is allergic sensitization as a cause of atopic asthma?
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过敏性过敏作为特应性哮喘的原因有多重要？
DOI：
10.1016/j.alit.2017.10.005
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发表时间：
2018
影响因子：
6.8
通讯作者：
Hizawa N
中科院分区：
文献类型：
--
作者：
Kanazawa J;Masuko H;Yamada H;Yatagai Y;Sakamoto T;Kitazawa H;Iijima H;Naito T;Hirota T;Tamari M;Hizawa N
特应性，即对常见的环境过敏原过度产生特异性IgE，被认为是哮喘的重要致病因素，与发病年龄无关。一种理论范式已经形成，其中过敏原暴露产生过敏性致敏，持续暴露通过气道炎症、支气管高反应性和可逆性气流阻塞的发展导致临床哮喘。然而，一般来说，控制IgE水平的基因与介导哮喘易感性的基因几乎没有重叠;有些人坚持认为特应性是继发于哮喘的，而不是疾病的主要驱动因素。1对特应性皮炎儿童的遗传学研究表明，屏障蛋白（如聚丝蛋白）的缺陷通常使个体易患该病，这表明IgE反应性的增加可能继发于屏障失效。类似地，哮喘患者的气道上皮的完整性经常由于上皮细胞与细胞接触的丧失而被破坏。由于许多最近发现的哮喘易感基因在气道上皮中表达，气道上皮屏障的变化可能在过敏原的继发性致敏中起重要作用。（Cys 529/Tyr），支持有效的人鼻病毒C进入和复制，与特征为特应性，早发性，和气流阻塞。2我们还使用日本人群全基因组关联研究（GWAS）以及非日本人群既往GWAS中与FEV 1/FVC较低相关的16个基因的基因型信息构建了气流阻塞的多SNP遗传风险评分（GRS）3，4; GRS的增加可能反映了肺生长或发育失调，与特应性哮喘的特殊表型密切相关，早发性和气流阻塞有趣的是，这两个遗传因素，CDHR 3变异和气流阻塞的GRS，与特应性无关。同时，我们先前的研究表明，显示与IgE强相关的位点对哮喘的影响很小。5
Atopy, the excessive production of specific IgE in response to common environmental allergens, is believed to be an important causative factor for asthma, irrespective of age at onset. A theoretical paradigm has evolved in which allergen exposure produces allergic sensitization and continued exposure leads to clinical asthma through the development of airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction. In general, however, the genes controlling IgE levels have surprisingly little overlap with the genes mediating asthma susceptibility; some people insist that atopy is secondary to asthma, not a primary driver of the disease. 1 Genetic studies of children with atopic dermatitis have shown that defects in barrier proteins such as Filaggrin commonly predispose individuals to the disease, indicating that increases in IgE responsiveness may be secondary to barrier failure. Analogically, the integrity of the airway epithelium in patients with asthma is often disrupted with loss of epithelial cellecell contact. Because many of the recently identified susceptibility genes for asthma are expressed in airway epithelium, changes at the airway epithelial barrier may play a central role in secondary sensitization to allergens.We recently found that the CDHR3 variant (Cys529/Tyr), that supports efficient human rhinovirus C entry and replication, was associated specifically with a phenotype of adult asthma characterized by atopy, early-onset, and airflow obstruction. 2 We also constructed a multi-SNP genetic risk score (GRS) for airflow obstruction using genotype information for 16 genes associated with lower FEV1/FVC in a genome-wide association study (GWAS) of Japanese populations as well as in previous GWASs of non-Japanese populations 3, 4; an increased GRS, which may reflect deregulated lung growth or development, was strongly associated with a particular phenotype of asthma characterized by atopy, early-onset, and airflow obstruction. Interestingly, both genetic factors, the CDHR3 variant and the GRS for airflow obstruction, were not associated with atopy. Meanwhile, our previous study showed that loci showing strong association to IgE had minimal effects on asthma. 5