Introduction
IgE-mediated food allergy affects up to 8% of children1 and 10% of infants2 in Westernised countries, which means there is likely to be at least one food allergic child in every school classroom3. Currently there is no curative therapy for food allergy. The recent approval of Palforzia, a desensitising oral immunotherapy, offers patients temporary protection against accidental exposure to small amounts of peanut4, however drawbacks include the need for continued maintenance treatment alongside allergen avoidance, frequent treatment-related allergic reactions, and a lack of improvement in quality of life5. Consequently, management remains centred on allergen avoidance and timely management of allergic reactions that result from accidental exposure to allergen, which often includes carrying an EpiPen for treatment of anaphylaxis. The constant vigilance required to adhere to allergen avoidance, unpredictability of reactions and ever-present fear of a fatal reaction, together have a severe impact on quality of life, similar to that of a child with diabetes6.
Efforts to identify effective treatments for food allergy that retrain the immune system away from allergy towards remission and ultimately tolerance have been hampered by a limited understanding of the key immune changes underpinning these outcomes, which in turn reflects the limited number of treatments that have been shown to successfully induce remission of allergy7. Although a large number of oral immunotherapy trials have been completed to date, limitations in study design have hindered the ability to draw firm conclusions about mechanisms driving clinical outcomes. In particular there are major gaps in our understanding of immune pathways supporting lasting remission of allergy. Study limitations include small sample sizes, highly variable treatment schedules with differing maintenance doses and treatment durations, and a wide divergence on how clinical end points are defined8. Furthermore, most mechanistic studies have examined changes in treated vs untreated subjects, without taking account of varying clinical outcomes within the treated group, which prevents delineation of the mechanisms supporting short-term (desensitisation) compared to longer-term (remission) benefits. Amongst the mechanistic studies that were designed to investigate immune changes linked to a clinical outcome, most have focused on the outcome of desensitisation (a change in reaction threshold during food challenge); few have examined changes linked to remission (sustained unresponsiveness). Even fewer have examined long-term immune changes following cessation of active treatment. Here we discuss the current understanding of transcriptomic changes associated with food allergy and the specific clinical outcomes of desensitisation or remission following oral immunotherapy.