Markers of tolerance development to food allergens

Abstract

IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy.IgE-mediated food allergy represents the most important cause of anaphylaxis in childhood. While milk and egg allergy are associated with a high rate of natural tolerance development within the first 6 years of life, this is less clear for other food allergies. Consequently, once it is communicated the diagnosis persists often lifelong severely impacting the quality of life of the patient and the environment despite the recommendation to reconsider clinical tolerance development from time to time.Currently, avoidance, providing an emergency plan and teaching, is the standard of treatment; however, there is no cure or treatment that has reached the level of recommendation to re-induce tolerance to the symptom-eliciting food. Tolerance assessment occurs either via oral food challenges or due to unintended exposure. Given the cost and time intensiveness of oral food challenges and its potential harmfulness, there is eminent need to understand the process of tolerance development and define markers thereof to develop and monitor new treatment strategies for food allergy. This review aimed to provide an overview on recent advances regarding markers and mechanisms of tolerance development to food allergens.Oral tolerance in the context of food allergy is considered to occur if the antigen/food can be ingested without problems despite prolonged periods of avoidance, while the status of desensitization is strictly dependent on regular ingestion of the respective food in order to confer protection from allergic reactions. Currently, there is no general consensus on the exact time frame of avoidance and re-exposure that would allow the usage of the terminus tolerance that is considered equivalent to cure in the context of or...

Novel approaches and perspectives in allergen immunotherapy

“…The demands to OIT are high as consumption of allergen may result in severe symptoms . Adverse side‐effects during conventional OIT can be severe, and only half of the enrolled patients reach maintenance dose .…”

“…Adverse side‐effects during conventional OIT can be severe, and only half of the enrolled patients reach maintenance dose . Half again could be maintained on maintenance dose for planned duration of treatment, and between a quarter and half of these patients had sustained unresponsiveness or developed persistent tolerance . To improve this performance, treatment is attempted with hypoallergic allergens or under a blanket of anti‐IgE treatment to limit side‐effects .…”

“…To improve this performance, treatment is attempted with hypoallergic allergens or under a blanket of anti‐IgE treatment to limit side‐effects . Persistent biomarker changes associated with successful primary prevention and OIT are a reduction of skin prick test (SPT) response and improvement in basophil reactivity and sensitivity .…”

Goldmag-based enzyme-linked immunosorbent assay for determination of α-lactalbumin in milk

“…Recently, with the development of scientific and technological progress, great changes in people's living environment and food types have taken place, and the number of people suffered from food allergic disease has extensively increased (Ponce, Diesner, Szepfalusi, & Eiwegger, 2016). Dairy products are widely utilized in food industries due to their high protein content and balanced nutrition.…”

Therapeutic vaccines for allergic disease

“…This state of partial tolerance mirrors a natural pattern of partial desensitization in patients not undergoing AIT and study animals, 109 , 110 yet still increase the threshold of reactivity to an allergen, upon regular exposure to small doses which do not trigger a reaction. 111 – 114 Both these examples are reflections of basic mechanisms of allergy, which in itself is dose-dependent, as demonstrated in both human 115 – 119 and animal 116 , 120 , 121 studies. However, exceeding the threshold can lead to serious consequences, i.e., adverse symptoms, both in those “naturally partially desensitized” patients and patients undergoing AIT.…”