Objective

The origins of allergic diseases have traditionally been explained by immunoglobulin E–mediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support a broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases, such as (1) inherent epithelial barrier dysfunction; (2) loss of immune tolerance; (3) disturbances in the gut; and (4) organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease.

Data Sources

We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in the specific microbiome, and inherent genetic predisposition.

Study Selections

We performed a literature search targeting primary and review articles.

Results

We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders and evaluated immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is affected by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type 2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior.

Conclusion

Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.

中文翻译：

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过敏源来自系统途径。

目的

传统上，过敏性疾病的起源是由免疫球蛋白E介导的免疫反应来解释的，以解释哮喘，特应性皮炎，特应性鼻炎和食物过敏。对疾病起源的研究见解支持了诱发，引发或加剧过敏性疾病免疫力改变的多种因素，例如：（1）固有的上皮屏障功能障碍；（2）免疫耐受性下降；（3）肠道干扰；（4）特定器官的微生物组，饮食和年龄。在这里，我们讨论这些影响，共同形成对变态反应作为系统疾病的更好的理解。

数据源

我们总结了上皮功能障碍，环境影响，炎症，感染，特定微生物组改变和固有遗传易感性的最新进展。

研究选择

我们针对主要文章和评论文章进行了文献搜索。

结果

我们探讨了过敏性疾病早期生命起源的微生物-上皮-免疫相互作用，并评估了提示新疾病预防或干预策略的免疫机制。上皮表面的损伤是过敏性疾病各种表现形式的起源。作为环境刺激的传感器，肺，肠和皮肤的上皮受到微生物组变化，空气污染，饮食变化中的食物过敏原以及现代洗涤剂中化学物质的影响。这共同导致肺，皮肤或肠上皮表面改变，从而驱动特应性疾病的2型免疫反应。过敏性疾病的治疗和预防包括生物制剂，口服脱敏，靶向肠道微生物组改变和行为改变。

结论

了解过敏是一种系统疾病，将使我们能够更好地定义过敏性疾病的机制并改善其治疗。