Recent developments in understanding the mechanisms of food allergy

Abstract

Purpose of review The prevalence of food allergy is rising globally. This review will discuss recent discoveries regarding the immunologic mechanisms that drive the initial sensitization and allergic response to food antigens, which may inform prevention and treatment strategies. Recent findings Tolerance to food antigens is antigen-specific and promoted by oral exposure early in life and maternal transfer of immune complexes via breast milk. IgG can inhibit both the initiation and effector phases of allergic responses to food antigens in mice, and high levels of food-specific IgG4 are associated with acquisition of tolerance in humans. Disruption of the skin barrier provides a route for food sensitization through the actions of mast cells, type 2 innate lymphoid cells, and IL-33 signaling. Regulatory T cells (Tregs) promote acquisition of oral tolerance, although defects in circulating allergen-specific Tregs are not evident in children with established food allergy. Certain microbes can offer protection against the development of IgE and food allergic responses, while dysbiosis increases susceptibility to food allergy. Summary Tolerance to food antigens is antigen-specific and is promoted by oral exposure early in life, maternal transfer of immune complexes, food-specific IgG, Tregs, an intact skin barrier, and a healthy microbiome.

New Perspectives in Food Allergy

“…For example, sensitization can occur through altered skin, as in atopic dermatitis, or by food protein aerosols (inhalation route). In the case of pollen-food allergy syndrome, the patient is sensitized to inhaled pollen allergens that cross-react with food allergens [82]. Once produced, IgE anchors to the high-affinity receptor for their Fc fragment on the membrane of tissue mastcells and circulating basophils, whose cytoplasm contains vasoactive substances and mediators of anaphylaxis, such as histamine [61].…”

“…Skin barrier defects due to mutations of filaggrin, an essential protein for the skin barrier integrity, predispose to the onset of FA. Barrier function deficits can, therefore, facilitate allergic sensitization to food antigens [82,83].…”

“…The immune-modulating and anti-allergic effects of gut microbiota is also mediated by metabolites generated from their dietary fiber fermentation, including short chain fatty acids (SCFAs), which regulate the pool of gut Treg cells. In addition to gut microbiome, also the skin microbiome may modulate FA susceptibility: Staphylococcus aureus skin colonization increases the risk of developingsensitization to various food allergens in childhood [82]. Figure 1 illustrates the main mechanisms by which the breakdown of tolerance to food antigens can occur.…”

Recent advances in mechanisms of food allergy and anaphylaxis

“…However, the demonstration of a positive correlation between environmental non-oral peanut protein exposure levels and development of peanut allergy suggests non-oral environmental exposure as a potential route of sensitization 66 . The observed natural history of the “allergic march”, whereby individuals presenting with atopic dermatitis (AD) in infancy or early childhood proceed to develop concomitant sensitization to food and aeroallergens in later childhood and adult life, has led to the evolving concept of contribution from the skin as a route of food sensitization 67 – 71 . An archetypal example is AD, a common inflammatory skin disease in childhood affecting nearly 20–30% of the population and is associated with skin barrier disruption linked with mutations in human skin barrier genes filaggrin ( FLG ), serine peptidase inhibitor Kazal type 5 ( SPINK5 ), corneodesmosin ( CDSN ), and mattrin ( TMEM79 ) 72 – 74 .…”

Update on the Role of Allergy in Pediatric Functional Abdominal Pain Disorders: A Clinical Perspective

“…Multiple physiologic factors prevent immune reactions to foods, termed tolerance, including microbiome features and the intestinal barrier [ 28 ]. Importantly, “outgrowing” a food allergy is associated with the development of food-specific IgG rather than IgE [ 29 ].…”