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.