Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation

Mast cells are tissue-resident immune cells that function in both innate and adaptive immunity through the release of both preformed granule-stored mediators, and newly generated proinflammatory mediators that contribute to the generation of both the early and late phases of the allergic inflammatory response. Although mast cells can be activated by a vast array of mediators to contribute to homeostasis and pathophysiology in diverse settings and contexts, in this review, we will focus on the canonical setting of IgE-mediated activation and allergic inflammation. IgE-dependent activation of mast cells occurs through the high affinity IgE receptor, FcεRI, which is a multimeric receptor complex that, once crosslinked by antigen, triggers a cascade of signaling to generate a robust response in mast cells. Here, we discuss FcεRI structure and function, and describe established and emerging roles of the β subunit of FcεRI (FcεRIβ) in regulating mast cell function and FcεRI trafficking and signaling. We discuss current approaches to target IgE and FcεRI signaling and emerging approaches that could target FcεRIβ specifically. We examine how alternative splicing of FcεRIβ alters protein function and how manipulation of splicing could be employed as a therapeutic approach. Targeting FcεRI directly and/or IgE binding to FcεRI are promising approaches to therapeutics for allergic inflammation. The characteristic role of FcεRIβ in both trafficking and signaling of the FcεRI receptor complex, the specificity to IgE-mediated activation pathways, and the preferential expression in mast cells and basophils, makes FcεRIβ an excellent, but challenging, candidate for therapeutic strategies in allergy and asthma, if targeting can be realized.

An Overview of Environmental Risk Factors for Food Allergy

IgE-mediated food allergy is an increasing public health concern in many regions around the world. Although genetics play a role in the development of food allergy, the reported increase has occurred largely within a single generation and therefore it is unlikely that this can be accounted for by changes in the human genome. Environmental factors must play a key role. While there is strong evidence to support the early introduction of allergenic solids to prevent food allergy, this is unlikely to be sufficient to prevent all food allergy. The purpose of this review is to summarize the evidence on risk factors for food allergy with a focus the outdoor physical environment. We discuss emerging evidence of mechanisms that could explain a role for vitamin D, air pollution, environmental greenness, and pollen exposure in the development of food allergy. We also describe the recent extension of the dual allergen exposure hypothesis to potentially include the respiratory epithelial barrier in addition to the skin. Few existing studies have examined the relationship between these environmental factors with objective measures of IgE-mediated food allergy and further research in this area is needed. Future research also needs to consider the complex interplay between multiple environmental factors.

Food Protein-Induced Enterocolitis Syndrome: Healthcare Utilization and Referral Patterns Among a Pediatric Cohort

BACKGROUND: Food protein–induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy characterized by delayed, repetitive vomiting. FPIES has gained attention over the last few years and is becoming better recognized; however, there remains a lag in diagnosis. This study aimed to further explore this lag in diagnosis, as well as referral patterns and healthcare utilization, to determine areas for earlier recognition. METHODS: Data was obtained through retrospective chart reviews of pediatric FPIES patients at two hospital systems in New York. Charts were reviewed for age of symptom onset, age of diagnosis, FPIES episodes and healthcare visits prior to diagnosis, and reason/source of referral to allergy. A cohort of patients with IgE-mediated food allergy was reviewed for comparison. RESULTS: In total, 110 patients with FPIES were identified. The median length to diagnosis was 3 months, compared to 2 months in IgE-mediated food allergy (p < 0.05). Most referrals were from the pediatrician (68%) or gastroenterology (28%), none were from the ED. The most common reason for referral was concern of IgE-mediated allergy (51%), followed by FPIES (35%). CONCLUSION: This study demonstrates a lag in the diagnosis of FPIES and a lack of recognition of FPIES outside of the allergy community, as only one-third of the patients were considered to have FPIES prior to an allergy evaluation. Patients with profuse, repetitive vomiting 1- 4 hours after food ingestion, especially of common FPIES trigger foods, should be considered for diagnosis of FPIES, as these encounters provide an opportunity for early recognition.

Food and Aeroallergen Sensitization in IgE -Mediated Asthma in Egypt

Purpose: Identifying the distribution of allergens is valuable to the effective diagnosis and treatment of allergic disease. So, our aim is to explore the sensitization of food and aeroallergens in Egyptian patients with atopic asthma. Methods: Cross-sectional study recruited 268 Egyptian patients with atopic asthma. Asthmatic patients were assessed by the enzyme allegro sorbent test (EAST) method for specific IgE to a panel of 19 common regional inhaled allergens and 15 food allergens. Results and Discussion: One hundred percent of the patients were sensitive to at least one allergen. Allergy to food allergens only was 2.9%; inhaled allergens only were 26.2% and both were70.9%. Fungi (62%) were the most frequent sensitizing aeroallergen amongst our asthmatic patients, followed by the pollen allergens (42.5%) and house dust mites (HDMs) (26%). Cows’ milk (30.5%) was the most frequent sensitizing food amongst our asthmatic patients, followed by eggs (22.4%) and fish (21.6%). Mono-sensitized patients accounted for 6.7% of all cases, while polysensitized was 93.3%. Moderate and severe asthma showed a significantly higher frequency of polysensitization compared to mild asthma. Conclusion: Fungi and cow's milk are the chief sensitizing allergens in Egyptian patients with atopic asthma. This study represents the first report of sensitization in atopic adult asthma using a large extract panel in Upper Egypt.

Food Allergy Prevention and Management in Children

Food allergy is a reaction mediated by immunological mechanisms that cause various symptoms in susceptible individuals while harmless in individuals who are not sensitive to the specific allergen. The reactions that take place are divided into three: IgE-mediated reactions, non-IgE-mediated reactions, and mixed-type reactions. While many types of food have the potential to cause allergen reactions, fewer foods are responsible for the most clinically severe reactions and for the majority of reported cases. Food allergy, which is increasingly common worldwide, is becoming an important public health problem. Although there are no clear epidemiological data, the prevalence of food allergy varies between 6-10% in preschool children and decreases to 2-5% in adulthood. Food allergy has long been recognized as a pediatric disease, as most cases tend to begin in childhood and disappear with growth. There is increasing evidence to support the role of early administration of potential food allergens to prevent food allergy. The management process of food allergy cases includes plans and innovative treatment strategies aimed at a personalized approach.

COVID-19 Vaccine Anaphylaxis: Current Evidence and Future Approaches

Vaccine anaphylaxis is rare; however, severe allergic reactions after administration of a coronavirus disease 2019 (COVID-19) vaccines have been reported. Excipients in the vaccine may play a role in severe allergic reactions post-vaccination. Various mechanisms, including IgE-mediated pathways, direct mass cell stimulation via the Mas-related G protein-coupled receptor-X2, and complement pathway activation, have been proposed to cause the anaphylaxis. Skin testing, using the basophil activation test, has been used to clarify the mechanism of the anaphylaxis and provide safety information for the next injection. Here, we review the current evidence and suggested approaches for patients who experienced an immediate severe allergic reaction to the first dose of a COVID-19 vaccine.