Is Oral Immunotherapy the Cure for Food Allergies?
Is Oral Immunotherapy the Cure for Food Allergies?
Purpose of review To review current evidence on food oral immunotherapy (OIT).
Recent findings Desensitized state, defined as the ingestion of a substantial amount of food in the home diet that protects from severe reactions to accidental exposures, can be achieved by approximately 50–75% of the children treated with OIT. The rate of permanent tolerance is unknown; the longer duration of OIT may result in permanent tolerance. Side effects are common both during the initial dose escalation and during home dosing. Most reactions are mild (oral pruritus, abdominal discomfort, and rashes) and decrease in frequency with the longer duration of OIT. Severe reactions treated with epinephrine have been reported during home dosing. Factors associated with increased risk of reactions to previously tolerated doses during home dosing include exercise, viral infection, dosing on empty stomach, menses, and asthma exacerbation.
Summary These preliminary data on OIT are encouraging. Additional studies must answer multiple questions including optimal dose, ideal duration of oral/sublingual immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment and need for patient protection during home administration. Until these questions are answered in rigorous multicenter randomized and placebo-controlled trials, OIT remains an experimental approach with not sufficiently well established risk-to-benefit ratio.
Food allergy prevalence is increasing worldwide. In the US, the Centers for Disease Control (CDC) reported an increase by 18% in the past two decades. The prevalence of peanut allergy doubled in the recent years and now reaches 1–2% in young children in the US, UK, Canada, and Australia. In parallel, food-induced anaphylaxis is also increasing. Currently the only treatment for food allergy is strict dietary avoidance and thus therapies for food allergy are urgently needed. The promising therapies under investigation are both allergen-specific and nonspecific. Not surprisingly, these therapies focus on the foods most frequently inducing severe anaphylactic reactions (peanut, tree nuts, shellfish) and the most common food allergens such as cow's milk and egg. Nonspecific therapies for food-induced anaphylaxis include monoclonal anti-IgE antibody, which increased the threshold dose for peanut in peanut-allergic individuals and Chinese herbal medications, which prevented peanut anaphylaxis in an animal model, for which human studies are ongoing. Allergen-specific therapies include oral, sublingual, and cutaneous immunotherapy (desensitization), mutated recombinant proteins, which are deficient in their IgE-binding activity, co-administered with heat-killed Escherichia coli to generate maximum immune response. Table 1 summarizes the therapies other than OIT that are being currently investigated in the human trials.
An approach that attracts a significant interest of the public and media as well as scientific community, is the food oral immunotherapy (OIT). A successful OIT was first reported in the early 20 century in a boy with severe anaphylactic allergy to egg. At present, OIT to food is a subject of many ongoing studies. As food allergy most likely results from the failure of development or the breakdown of normal oral tolerance (such as following a gastrointestinal infection or sensitization to the cross-reactive allergen via inhalation), the oral route of administration takes advantage of the cells and immune pathways involved in the induction of oral tolerance. Animal studies suggest that the high-dose feeding of an antigen results in the state of nonresponsiveness due to anergy or deletion of antigen-specific T lymphocytes, whereas continuous low-dose ingestion may induce protective suppressive responses from regulatory T cells. In contrast, intermittent feedings or nonoral exposures (e.g. cutaneous or inhalational) may induce IgE sensitization and allergic symptom upon food ingestion.
Abstract and Introduction
Abstract
Purpose of review To review current evidence on food oral immunotherapy (OIT).
Recent findings Desensitized state, defined as the ingestion of a substantial amount of food in the home diet that protects from severe reactions to accidental exposures, can be achieved by approximately 50–75% of the children treated with OIT. The rate of permanent tolerance is unknown; the longer duration of OIT may result in permanent tolerance. Side effects are common both during the initial dose escalation and during home dosing. Most reactions are mild (oral pruritus, abdominal discomfort, and rashes) and decrease in frequency with the longer duration of OIT. Severe reactions treated with epinephrine have been reported during home dosing. Factors associated with increased risk of reactions to previously tolerated doses during home dosing include exercise, viral infection, dosing on empty stomach, menses, and asthma exacerbation.
Summary These preliminary data on OIT are encouraging. Additional studies must answer multiple questions including optimal dose, ideal duration of oral/sublingual immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment and need for patient protection during home administration. Until these questions are answered in rigorous multicenter randomized and placebo-controlled trials, OIT remains an experimental approach with not sufficiently well established risk-to-benefit ratio.
Introduction
Food allergy prevalence is increasing worldwide. In the US, the Centers for Disease Control (CDC) reported an increase by 18% in the past two decades. The prevalence of peanut allergy doubled in the recent years and now reaches 1–2% in young children in the US, UK, Canada, and Australia. In parallel, food-induced anaphylaxis is also increasing. Currently the only treatment for food allergy is strict dietary avoidance and thus therapies for food allergy are urgently needed. The promising therapies under investigation are both allergen-specific and nonspecific. Not surprisingly, these therapies focus on the foods most frequently inducing severe anaphylactic reactions (peanut, tree nuts, shellfish) and the most common food allergens such as cow's milk and egg. Nonspecific therapies for food-induced anaphylaxis include monoclonal anti-IgE antibody, which increased the threshold dose for peanut in peanut-allergic individuals and Chinese herbal medications, which prevented peanut anaphylaxis in an animal model, for which human studies are ongoing. Allergen-specific therapies include oral, sublingual, and cutaneous immunotherapy (desensitization), mutated recombinant proteins, which are deficient in their IgE-binding activity, co-administered with heat-killed Escherichia coli to generate maximum immune response. Table 1 summarizes the therapies other than OIT that are being currently investigated in the human trials.
An approach that attracts a significant interest of the public and media as well as scientific community, is the food oral immunotherapy (OIT). A successful OIT was first reported in the early 20 century in a boy with severe anaphylactic allergy to egg. At present, OIT to food is a subject of many ongoing studies. As food allergy most likely results from the failure of development or the breakdown of normal oral tolerance (such as following a gastrointestinal infection or sensitization to the cross-reactive allergen via inhalation), the oral route of administration takes advantage of the cells and immune pathways involved in the induction of oral tolerance. Animal studies suggest that the high-dose feeding of an antigen results in the state of nonresponsiveness due to anergy or deletion of antigen-specific T lymphocytes, whereas continuous low-dose ingestion may induce protective suppressive responses from regulatory T cells. In contrast, intermittent feedings or nonoral exposures (e.g. cutaneous or inhalational) may induce IgE sensitization and allergic symptom upon food ingestion.
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