Recent developments and highlights in food allergy

Abstract

The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

New Perspectives in Food Allergy

“…CD103+ DCs transport the captured antigens to Peyer's patches and mesenteric lymphnodes and drive the homing of B lymphocytes secreting mucosal IgA in the gut, thus contributing to the maintenance of a specific immune tolerance [92]. IgGs, in particular, specific IgG4, can inhibit the initiation as well as the effector phases of allergic responses, thus also contributing to the acquisition of oral tolerance to food antigens [2].…”

“…Moreover, tolerogenic Treg lymphocytes are suppressed, reprogrammed, and transformed into pro-allergic IL-4-producing cells [98,99]. Among the other cell types involved in tolerance disruption, innate lymphoid cells of type 2 (ILC2), similar to Th2 lymphocytes but lacking specificity for the antigen, and IL-9-producing cells (Th9 cells), which are mucosal mastcells capable of producing various inflammatory cytokines and capable to suppress the function of Tregcells, have been recently recognized [2,100]. All of them increase the vicious circle which leads, through an autocrine loop, to the increase in the intestinal mastcell pool [20,92,101].…”

“…Damaged skin epithelial cells release inflammatory cytokines, such as TSLP, IL-25, and IL-33, that induce cutaneous DCs and other cell types to shift immune responses from tolerance to hypersensitivity. Furthermore, the cytokines derived from tissues, in particular IL-33, also intervene in determining allergic sensitization and in triggering reactions, through the activation of ILC2, which in turn produce IL-4 and IL-13 [2]. IL-25, IL-33, and TSLP, derived by damaged epitheliocytes, function as alarmins and are involved in sensitization and maintenance of allergic reactions.…”

“…IL-25, IL-33, and TSLP, derived by damaged epitheliocytes, function as alarmins and are involved in sensitization and maintenance of allergic reactions. These cytokines facilitate the onset and development of allergic responses to foods and are, therefore, becoming targets to treat in the management of FA [2]. In particular, IL-33 is an alarmin that also acts as a Th2 cytokine, promoting allergic reactions [104,105].…”

“…Food allergy (FA) is an adverse reaction to a specific food antigen, normally harmless to the healthy population, which is mediated by immunological mechanisms and arises in an individual susceptible to that specific allergen [1,2].…”