A general strategy for de novo immunotherapy design: the active treatment of food allergy

Abstract

IgE-mediated food allergy (FA) has been emerging as a public health priority. It is a potentially life-threatening condition with negative impact on the quality of life of patients and their family and its prevalence is increasing in westernized countries in the recent two decades. The current standard approach to FA consists of the strict avoidance of the triggering food. However, an elimination diet may be difficult and frustrating, above all for those foods (e.g. milk and egg) that are pivotal in the common diet. Oral immunotherapy (OIT) may increase the amount of food that the patient can intake without reaction and reduce the risk of potential life-threatening allergic reactions. It is currently considered the most promising treatment for FA. However, many gaps are still unsolved. Areas covered: The aim of this review is to shed light on the current evidence and the main needs in OIT in order to stimulate the development of longitudinal, prospective, and well-designed studies with the final goal of a 'precision medicine.' Expert commentary: Clinical trials for OIT conducted so far are extremely heterogeneous. The aim in the near future is to identify the most suitable candidates to OIT and algorithms for treatments tailored on well-characterized subpopulations of patients.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy

“…• Spontaneous resolution of food allergy in childhood: 49% to 79% (egg, milk, soy & wheat); peanut 20-27% 114 and tree nut (9%); 115 allergy is less likely to resolve in children with other atopic diseases, high IgE levels, large SPT wheal sizes and symptoms other than only urticaria (hives) or angioedema. 115 • Feasibility of allergen avoidance in real life: elimination diet often represents "an unrealistic therapeutic option"; 116 avoidance can fail (packaged food containing undeclared allergens, 117 118 cross-contamination, social activities involving food at school, work, restaurants and other public places) and requires a team effort, including increased awareness and education to avoid misconceptions and inconsistent knowledge of risks in public places such as restaurants. 111 • Impact of allergen avoidance on health: potentially unnecessary restrictive diets for food-allergic children 119 in and their siblings; 120 risk of inadequate intake of certain nutrients 121 (e.g., calcium with increased risk of osteoporosis 122 ), risk of eating disorders and other psychological problems 123 • Psychosocial impact: time-consuming and stressful preparation for social activities, bullying, isolation, fear and uncertainty about the risk of accidental ingestion and severe reaction, psychological distress and depression.…”

Food Allergies: Current and Future Treatments

“…Ideally, this active treatment enables an increase in the amount of food that the patient can intake without reacting during treatment (i.e., desensitization), reducing the risk of potential life-threatening allergic reactions in cases of accidental ingestion [8]. However, a more comprehensive goal of FA-AIT is the absence of symptoms after the intake of a normal serving of the culprit food despite a period of absence of exposure (i.e., tolerance), thus maintaining its efficacy after the discontinuation of the treatment [9]. The achievement of a persistent tolerance is still one of the unmet needs of FA-AIT, and it is currently recommended to consume the allergenic food in order to maintain the beneficial effects of desensitization [10].…”

Allergen immunotherapy for IgE‐mediated food allergy: There is a measure in everything to a proper proportion of therapy

“…FA represents both a promising and intriguing field of application for allergen immunotherapy especially in its oral form (OIT) . Currently, the use of fresh material or native food(s) is suggested to achieve the goal of desensitization .…”

“…FA represents both a promising and intriguing field of application for allergen immunotherapy especially in its oral form (OIT). [7][8][9] Currently, the use of fresh material or native food(s) is suggested to achieve the goal of desensitization. 25 On the other hand, there is a race to develop commercial treatment for FA fueled by increasing prevalence and severity of FA in children.…”

“…However, a more desirable goal for FA‐AIT lies on the effectiveness after the discontinuation of the treatment. The latter is also known as “tolerance” or “post‐discontinuation effectiveness” or “sustained unresponsiveness” and refers to the absence of symptoms after ingestion of a normal serving of the culprit food despite a period of absence of exposure; it remains still one of the major issue to be clarified . Notwithstanding, after build‐up phase, and having achieved the maintenance dose, it is overall recommended to consume the allergenic food in order to maintain the beneficial effects of desensitization.…”