Treatment Of IgE-mediated Food Allergy Research Articles

Nutritional and Psychosocial Impact of Food Allergy in Pediatric Age

Treatment of IgE-mediated food allergy involves avoiding the food causing the allergic reaction. In association, an action plan for allergic reactions is indicated, sometimes including self-injectable adrenaline. In addition to these dietary and medical implications, there are two equally important ones: nutritional and psychosocial. From a nutritional point of view, it is known that children suffering from food allergy have a growth delay in height and weight compared to their non-allergic peers. Specifically, this condition is directly related to the specific food excluded from the diet, the number of foods excluded and the duration of the elimination diet. From a psychosocial point of view, the child often cannot eat the foods other guests eat. Children with food allergy may perceive an aura of parental anxiety around their mealtime and may be afraid that what they eat could have harmful consequences for their health. Furthermore, children’s and their parents’ quality of life appears to be affected. The need to manage the allergy and the nutritional and psychosocial problems positions the pediatric nutritionist and the child neuropsychiatrist as support figures for the pediatric allergist in managing the child with food allergy.

The Immunobiology and Treatment of Food Allergy.

IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper Tcell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several host-related and environmental factors impacting the risk of IgE-FA development have been identified. Mounting evidence supports the role of an impaired epithelial barrier in the development of IgE-FA, with exposure of allergens through damaged skin and gut epithelium leading to the aberrant production of alarmins and activation of TH2-type allergic inflammation. The treatment of IgE-FA has historically been avoidance with acute management of allergic reactions, but advances in allergen-specific immunotherapy and the development of biologics and other novel therapeutics are rapidly changing the landscape of food allergy treatment. Here, we discuss the pathogenesis and immunobiology of IgE-FA in addition to its diagnosis, prognosis, and treatment. Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Oral and Sublingual Immunotherapy for Treatment of IgE-Mediated Food Allergy.

Development of active therapies for IgE-mediated food allergy is a critical action step toward alleviating the adverse medical, psychosocial, and economic burdens on affected patients and families. Significant progress has been observed specifically in the application of single-allergen oral and sublingual immunotherapy for treatment of IgE-mediated food allergy, with emphasis on milk, egg, and peanut as the primary allergens. Oral immunotherapy (OIT) has demonstrated efficacy in promoting immunomodulatory effects that lead to the clinical outcome of desensitization, defined as reduced reactivity while on active OIT, in the majority of treated individuals; however, achievement of sustained unresponsiveness following cessation of therapy has been observed in a smaller subset of treated subjects. The potential therapeutic benefits of OIT must be carefully considered in light of the significant potential for adverse events ranging from self-limited or easily treated oropharyngeal, respiratory or gastrointestinal symptoms, to persistent abdominal complaints that lead to cessation of therapy in an estimated 10-15% of treated individuals. To date, the majority of studies have focused on single-allergen OIT approaches; however, multi-allergen OIT has shown promise in initial trials and is the subject of ongoing investigation to address the complex needs of multi-food allergic individuals. Sublingual immunotherapy (SLIT) has been utilized for the treatment of food allergy and pollen-food allergy syndrome, demonstrating moderate efficacy, a favorable safety profile and variable tolerability, with oropharyngeal symptoms most commonly observed. Although studies directly comparing OIT and SLIT are limited, in general, the favorable safety profile associated with SLIT comes at the expense of reduced efficacy, while the more robust clinical effects observed with OIT come at the risk of potentially intolerable, treatment-limiting side effects. Future investigation to address specific knowledge gaps including optimal dose, duration, age of initiation, maintenance schedule, mechanisms, predictors of risk and therapeutic response will be important to maximize efficacy, minimize risk and develop personalized, effective approaches to targeting food allergy.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

Food allergy: immune mechanisms, diagnosis and immunotherapy.

Food allergy is a pathological, potentially deadly, immune reaction triggered by normally innocuous food protein antigens. The prevalence of food allergies is rising and the standard of care is not optimal, consisting of food-allergen avoidance and treatment of allergen-induced systemic reactions with adrenaline. Thus, accurate diagnosis, prevention and treatment are pressing needs, research into which has been catalysed by technological advances that are enabling a mechanistic understanding of food allergy at the cellular and molecular levels. We discuss the diagnosis and treatment of IgE-mediated food allergy in the context of the immune mechanisms associated with healthy tolerance to common foods, the inflammatory response underlying most food allergies, and immunotherapy-induced desensitization. We highlight promising research advances, therapeutic innovations and the challenges that remain.

Oral food desensitization

The common treatment of IgE-mediated food allergy is to avoid the offending item and educating patients on appropriate emergency measures. Recently, attempts to gain food tolerance with oral administration of increasing doses of the offending food have become frequent. Desensitization procedures are risky and safety is a priority. Their success depends on the individual allergic characteristics and the modality of food administration. Most schedules adopted in the desensitization protocols are empiric and not regular, as requirements of safety would require. Some oral food desensitization schedules were compared in order to verify whether the increments between doses were regular. Through a mathematic formula adopted by the musicians to tune instruments in the 17th Century, including Bach, I describe a method to calculate an increment factor by which a schedule of food administration that ensures an absolutely constant increment between doses can be achieved. This method can prove useful for every situation in which a gradual dose increment is needed (food, drugs in an experimental setting, specific immunotherapy with inhalants or venom insect allergens). All calculations can be done also without a computer, and this is particularly important if modern technologies are not available, such as in developing countries.I propose calling this method 'Building an Allergen-augmentation Curve Harmoniously (BACH)'.

Prevention and Treatment of Poly-Lysine Modified Arah2 DNA Vaccine On Arah2 Protein Induced Allergy

Treatment of IgE-mediated food allergy with standard protein-based allergen immunotherapy has proven both unsuccessful and hazardous. Allergen gene vaccination represents a promising alternative, but low efficiency in immunization represent a major limitation for efficient gene vaccination. The current study is to explore the prophylactic and therapeutic efficacy of poly-l-lysine (PLL) modified peanut DNA vaccine on peanut protein induced allergy.

Sublingual vs Oral Immunotherapy for Food Allergy

The incidence of food allergy in developed countries has increased in recent years, escalating the need to find a suitable form of treatment as an alternative to current management, which includes strict avoidance and ready availability of injectable epinephrine (adrenaline). Allergen immunotherapy is currently being studied for use in the treatment of IgE-mediated food allergy to the most common foods, including peanut, tree nut, milk and egg. Two modalities, oral immunotherapy (OIT) and sublingual immunotherapy (SLIT), have shown great promise. Both OIT and SLIT have been able to desensitize subjects to varying degrees, but the two treatment methods differ in doses that can be achieved, duration of treatment, safety profile and ease of use outside the research setting, among other aspects. More research is needed to conclude which mode of treatment is more effective in inducing long-term tolerance with the least amount of serious adverse reactions. However, OIT and SLIT show great promise, and a widespread treatment for food allergy may be within reach.

IgE-mediated allergen gene vaccine platform targeting human antigen-presenting cells through the high-affinity IgE receptor

Treatment of IgE-mediated food allergy with standard protein-based allergen immunotherapy has proved both unsuccessful and hazardous. Allergen gene vaccination represents a promising alternative, but difficulties in gene targeting and expression in antigen-presenting cells represent a major limitation for efficient gene vaccination. We sought to construct a genetically engineered human epsilon-polylysine (EPL) fusion protein that binds allergen gene expression systems and targets the gene vaccine complex to antigen-presenting cells through the interaction of EPL and the high-affinity receptor for IgE for efficient allergen gene vaccination. Genetic engineering was used to design and produce the EPL fusion gene, consisting of the human CHepsilon2-4 linked to 55 lysine residues, and the conventional approaches were used to characterize the biologic features of EPL. EPL was assembled as functional dimers and capable of binding DNA plasmids in both an EPL protein and plasmid DNA concentration-dependent manner. EPL targeted plasmid DNA to the high-affinity receptor for IgE on cell surfaces and increased the model gene uptake/expression. The EPL-DNA complexes were shown not to trigger mast cell degranulation. EPL is able to function as a gene carrier system to target allergen gene to the high-affinity receptor for IgE-expressing cells through ligand receptor-mediated interactions.