Allergy: Mechanistic insights into new methods of prevention and therapy

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Abstract

In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.

Abstract

Insights into the molecular mechanisms underlying allergic diseases have led to changes in preventative guidelines and new treatments.

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Most cited references 119

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Randomized trial of peanut consumption in infants at risk for peanut allergy.

George du Toit, Graham Roberts, Peter Sayre … (2015)

The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy.

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Prevalence and Severity of Food Allergies Among US Adults

Ruchi Gupta, Christopher M. Warren, Bridget M Smith … (2019)

This survey study provides nationally representative estimates of the distribution, severity, and factors associated with adult food allergy in the United States.

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Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?

Cezmi Akdis (2021)

There has been a steep increase in allergic and autoimmune diseases, reaching epidemic proportions and now affecting more than one billion people worldwide. These diseases are more common in industrialized countries, and their prevalence continues to rise in developing countries in parallel to urbanization and industrialization. Intact skin and mucosal barriers are crucial for the maintenance of tissue homeostasis as they protect host tissues from infections, environmental toxins, pollutants and allergens. A defective epithelial barrier has been demonstrated in allergic and autoimmune conditions such as asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, coeliac disease and inflammatory bowel disease. In addition, leakiness of the gut epithelium is also implicated in systemic autoimmune and metabolic conditions such as diabetes, obesity, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and autoimmune hepatitis. Finally, distant inflammatory responses due to a 'leaky gut' and microbiome changes are suspected in Alzheimer disease, Parkinson disease, chronic depression and autism spectrum disorders. This article introduces an extended 'epithelial barrier hypothesis', which proposes that the increase in epithelial barrier-damaging agents linked to industrialization, urbanization and modern life underlies the rise in allergic, autoimmune and other chronic conditions. Furthermore, it discusses how the immune responses to dysbiotic microbiota that cross the damaged barrier may be involved in the development of these diseases.