Immunotherapy-possibilities and dangers in food allergy
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Food allergy is a growing health concern in the westernized world with approximately 6% of children suffering from it. A lack of approved treatment has led to strict avoidance of the culprit food proteins being the only standard of care. Nowadays in-depth research is conducted to evaluate the possible use of allergen-specific immunotherapy (SIT) as an active therapeutic option for food allergy. Various routes of administration for the immunotherapy are investigated, including subcutaneous, oral, sublingual, and epicutaneous and some appear to be successful in inducing desensitization. Most research has been conducted with oral immunotherapy due to its efficacious and relatively safe profile. Increasing interest is dedicated to safer and more convenient approaches, such as sublingual and epicutaneous SIT, however, doubts exist about their possible capacity to induce tolerance. Although the underlying mechanisms of successful desensitization with SIT are not yet clear, evidence suggests that those involve suppression of mast cell and basophil reactivity, reduction in allergen-specific IgE and increase in allergen-specific IgG4 antibodies, as well as stimulation of natural or de novo induced regulatory T cells and skewing of the T cell response from the pro-allergic Th2 to the Th1 phenotype. The high frequency of allergic adverse reactions of the various approaches and the inability to achieve permanent oral tolerance have highlighted the need of refinements in the strategies and the potential use of tolerazing adjuvants. A promising strategy for preventing IgE cross-linking and thus enhancing safety of SIT, while still activating T cells, is the use of tolerogenic peptides. The implementation of a tolerizing Treg/Th1-polarizing adjuvant, such as a specific mixture of non-digestible oligosaccharides, into immunotherapy approaches has the potential of not only increasing the chance of achieving permanent state of tolerance, but also improving the safety and tolerability of the therapy. Immunotherapy for food allergy is still not ready for the clinic, but current and upcoming studies are dedicated at collecting enough evidence for the possible implementation of allergen-specific immunotherapy as a standard treatment for food allergy.