Globally, the prevalence of food allergies in children is on the rise. Earlier onset allergies to milk, eggs, and wheat in children have a better prognosis, while allergies to peanuts, tree nuts, and seafood may persist. Food immune tolerance refers to a phenomenon where antigen-specific T cells and B cells are not activated and produce specific immune response cells or antibodies, as a result of food antigen stimulation. Therefore, they do not produce an immune response. However, a normal immune response to other antigens is still maintained. If food immune tolerance is not achieved, allergy symptoms will recur, lowering the quality of life and causing an economic burden. Recently, a large-scale prospective study discussed the latest developments in allergies to various foods, including milk, eggs, wheat, and peanuts. This blog will delve into the interpretation of this study.
Mechanism of IgE-Mediated Food Allergy Immune Tolerance
The mechanism behind the natural resolution of food allergies is unclear, but regulatory B cells, IgG4 antibodies, and FoxP3+ regulatory T cells may play important roles in inducing immune tolerance. Tolerance to food allergens is primarily driven by antigen-presenting cells in the gut lamina propria that promote T-cell differentiation. CD103+ dendritic cells migrating from the lamina propria of the mesenteric lymph nodes can promote the development of gut regulatory T cells through several mechanisms involving transforming growth factor-B (TGF-B), retinoic acid, and transmembrane proteins. Regulatory T cells, especially those characterized by CD25 expression of Foxp3+ regulatory T cells, play a crucial role in oral tolerance. Gene knockout of FoxP3 in mice results in multi-organ allergic inflammatory responses, while adoptive transfer of regulatory T cells can suppress allergic responses in food allergy animal models. Higher numbers of milk-specific CD4+ CD25+ T regulatory cells are associated with the acquisition of oral immune tolerance to milk. These regulatory T cells can also produce a variety of inhibitory cytokines, such as IL-10 and TGF-B. L-10 suppresses Th2 immune responses and allergic inflammation by reducing IgE production and promoting allergen-specific IgG4 responses. Children naturally tolerant to eggs or peanuts have markedly increased IL-10 expression levels in CD4+ T regulatory cells, CD25+CD127l0 cells, and FoxP3+ cells.
Natural Course of Specific Food Allergies
Numerous studies have shown that IgE-mediated allergies to milk, eggs, wheat, and soy are more likely to disappear during childhood, while allergies to peanuts, tree nuts, and seafood tend to persist. A domestic longitudinal observational study showed that 44% and 64% of children diagnosed with IgE-mediated cow’s milk protein allergy before 24 months of age respectively tolerated cow’s milk protein at 24 and 36 months of age, indicating that children with cow’s milk protein allergy can mostly acquire tolerance early.
Factors Affecting Food Allergy Immune Tolerance
Thus far, there is still insufficient evidence of biomarkers predicting the decrease or persistence of food allergies. Factors associated with food allergy immune tolerance include age at diagnosis, concomitant other allergic diseases and their severity, symptom severity upon allergen intake, the size of the skin prick test wheal, sIgE levels, the rate of change in sIgE levels or the size of the skin prick test wheal, the ratio of sIgE to IgG4, diet, gut microbiota and intervention measures. In conclusion, the establishment of food immune tolerance is influenced by multiple factors, and in clinical practice, detrimental factors should be avoided, beneficial factors used, food allergies prevented, and the formation of food immune tolerance accelerated.
How to Assess Food Allergy Immune Tolerance
As the course of food allergies varies based on food type, patient age, and test results, clinicians must integrate available information to assess relief from food allergies. Serum sIgE levels or skin prick tests are among the few methods suitable for repeated use in clinical practice to monitor the natural course of food allergies. When considering oral food challenges (OFC) to assess food allergy immune tolerance, clinicians should consider factors such as patient age, the importance of the allergenic food in the diet, past reaction history, comorbidities (especially severe atopic dermatitis, uncontrolled asthma or gastroesophageal diseases), and patient and family preferences.
Discussion
Previous studies suggest that food allergy immune tolerance is influenced by factors such as gastrointestinal function, the child’s immunity, levels of vitamins and trace elements, family feeding practices, and other environmental factors. Promoting food allergy immune tolerance involves guiding patients to ingest probiotics, cultivating healthy dietary habits, and appropriately supplementing vitamins and trace elements. To provide optimal treatment and enhance the quality of life for food allergy patients, clinicians must understand the individual’s natural course of food allergies, educating patients and caregivers while guiding proper feeding practices.