The Origins of Allergy from a Systems Approach. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Krempski, J. W., Dant, C. n., Nadeau, K. C. 2020


The origin of allergic disease has traditionally been explained by IgEmediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases: inherent epithelial barrier dysfunction, loss of immune tolerance, disturbances in gut and organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease.We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in specific microbiome, and inherent genetic predisposition.We performed a literature search targeting primary and review articles.We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders, and examined 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 impacted 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.Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.

View details for DOI 10.1016/j.anai.2020.07.013

View details for PubMedID 32702411