The Road Toward Transformative Treatments for Food Allergy

Abstract

A series of landmark studies have provided conclusive evidence that the early administration of food allergens dramatically prevents the emergence of food allergy. One of the greatest remaining challenges is whether patients with established food allergy can return to health. This challenge is particularly pressing in the case of allergies against peanut, tree nuts, fish, and shellfish which are lifelong in most patients and may elicit severe reactions. The standard of care for food allergy is allergen avoidance and the timely administration of epinephrine upon accidental exposure. Epinephrine, and other therapeutic options like antihistamines provide acute symptom relief but do not target the underlying pathology of the disease. In principle, any transformative treatment for established food allergy would require the restoration of a homeostatic immunological state. This may be attained through either an active, non-harmful immune response (immunological tolerance) or a lack of a harmful immune response (e.g., anergy), such that subsequent exposures to the allergen do not elicit a clinical reaction. Importantly, such a state must persist beyond the course of the treatment and exert its protective effects permanently. In this review, we will discuss the immunological mechanisms that maintain lifelong food allergies and are, consequently, those which must be dismantled or reprogrammed to instate a clinically non-reactive state. Arguably, the restoration of such a state in the context of an established food allergy would require a reprogramming of the immune response against a given food allergen. We will discuss existing and experimental therapeutic strategies to eliminate IgE reactivity and, lastly, will propose outstanding questions to pave the road to the development of novel, transformative therapeutics in food allergy.

Monitoring memory B cells by next generation ImmunoSpot® provides insights into humoral immunity that measurements of circulating antibodies do not reveal

“…In contrast, all subjects with PCR-veri ed infection, harbored S and N antigen-speci c IgG + ASC. These ndings are consistent with the notion that clonal expansions to detectable frequency levels, class-switching, and Thus, our detection system enables identi cation of IgE + ASC, but whether IgE + B mem exist in vivo, or whether they switch de novo to IgE in vivo or in vitro is controversial[42,43]. and 10 million can be frozen per cryovial permitting the optimization of PBMC utilization when planning experiments (N. Becza, manuscript in preparation).24.…”

The origins and longevity of IgE responses as indicated by serological and cellular studies in mice and humans

“…The majority of milk and egg allergies resolve by age 12 61,63,64 . By contrast, allergies to peanuts, tree nuts, fish, and shellfish, although less frequent, are unlikely to resolve 64–66 . That is, there is something about certain allergens that affects the disease prognosis.…”

“…61 , 63 , 64 By contrast, allergies to peanuts, tree nuts, fish, and shellfish, although less frequent, are unlikely to resolve. 64 , 65 , 66 That is, there is something about certain allergens that affects the disease prognosis. Allergies likely to persist into adulthood are associated with higher amounts of serum IgE, with distinctive and diverse IgE‐binding epitope patterns on allergen, more diverse allergen recognition, and different V gene use of B cells relative to individuals that are tolerant to allergen or regularly ingesting it.…”

Food allergy, mechanisms, diagnosis and treatment: Innovation through a multi‐targeted approach

“…Advancements in the field of allergen immunotherapy and the development of biologics and other novel therapies have continued to push towards safe and effective options for FA treatment. 10 Additionally, recent efforts have shifted focus to investigate innovations in the realm of diagnostics, endotyping, and primary prevention. In this review, we provide an overview of major recent developments in the diagnosis, prevention, and treatment of FA (Box 1).…”

“…While the first approved treatment for peanut allergy (PA) is now available, 9 the current standard of care for other food allergens remains strict avoidance. Advancements in the field of allergen immunotherapy and the development of biologics and other novel therapies have continued to push towards safe and effective options for FA treatment 10 . Additionally, recent efforts have shifted focus to investigate innovations in the realm of diagnostics, endotyping, and primary prevention.…”