[The advances on oral tolerance induction for prevention of egg allergy in infants].

The prevalence of food allergy is increasing worldwide and seriously affects the living quality of patients and their families. Egg allergy is one of the commonest forms of food allergy. The traditional regimen is to delay the introduction of eggs to infant complementary foods, which is not able to reduce the prevalence of egg allergies and causes negative effects on infants' physical and psychological conditions. Oral tolerance therapy is an approach to establish immune tolerance by the active suppression of specific immune responses to antigens in the gastrointestinal tract. The development of oral tolerance through early introduction of eggs to infant complementary has proven effective in randomized controlled trials, which has been incorporated into infant feeding guidelines in many countries. This article focuses on the mechanism, efficacy and safety of oral tolerance induction in the prevention of egg allergy.

Changes of structure properties and potential allergenicity of ovalbumin under high hydrostatic pressures.

Egg proteins, notably ovalbumin (OVA), contribute to a prevalent form of food allergy, particularly in children. This study aims to investigate the impact of high hydrostatic pressure (HHP) treatment at varying levels (300, 400, 500, and 600 MPa) on the molecular structure and allergenicity of OVA. The structure of HHP-treated OVA was assessed through fluorescence spectroscopy, circular dichroism spectroscopy, and molecular dynamics (MD) simulation. HHP treatment (600 MPa) altered OVA structures, such as α-helix content decreased from 28.07 % to 19.47 %, and exogenous fluorescence intensity increased by 8.8 times compared to that of the native OVA. The free sulfhydryl groups and zeta potential value were also increased with HHP treatment (600 MPa). ELISA analysis and MD simulation unveiled a noteworthy reduction in the allergenicity of OVA when subjected to 600 MPa for 10 min. Overall, this study suggests that the conformational changes in HHP-treated OVA contribute to its altered allergenicity.

Role of serum-specific immunoglobulin E in egg allergy: a comprehensive study of Portuguese pediatric patients.

INTRODUCTION: Food allergies represent a growing public health concern, particularly among children. This study aims to examine egg allergy in pediatric patients and analyze the value of serum-specific immunoglobulin E (sIgE) levels as predictive biomarkers for oral food challenge (OFC) outcomes. METHODS: Retrospective study, involving pediatric patients with suspected IgE-mediated egg allergy, conducted at a tertiary hospital. RESULTS: Data from 176 pediatric patients were analyzed, revealing a higher male prevalence (59.1%). Most cases (40.3%) presented symptoms in the first year of life, predominantly mucocutaneous symptoms (46%). OFC results varied across various forms of egg presentation, with cooked egg being the most frequently tested food. Positive OFCs were observed in 14.6% (n = 36) of cases. The study identified specific egg protein biomarkers for positive OFC, with ovalbumin for raw egg (sIgE > 1.28 KUA/L; area under the curve [AUC] = 0.917; sensitivity [S] 100%; and specificity [Sp] 92%), ovomucoid for cooked egg (sIgE > 0.99 KUA/L; AUC = 0.788, 95%; S: 79%; and Sp: 74%), and ovomucoid for baked egg (sIgE> 4.63 KUA/L; AUC = 0.870; S: 80%; and Sp: 85%) showing predictive capacities. CONCLUSIONS: The findings underscore the importance of considering various forms of egg presentation in the diagnosis and management of egg allergy. The findings highlight the valuable discriminatory capacity and provided reliable biomarkers, such as ovalbumin for raw egg and ovomucoid for cooked and baked egg in risk assessment, aiding in predicting OFC outcomes and helping clinicians to make informed decisions in diagnosing and managing egg allergies, thus improving patient care and quality of life.

Traditional cooking methods decreased the allergenicity of egg proteins.

Egg allergy is one of the most common food allergies globally. This study aimed to assess the impact of four traditional cooking methods on the allergenicity of egg proteins using a comprehensive strategy, including simulated gastrointestinal digestion in vitro, serology experiments, a rat basophilic leukemia (RBL)-2H3 cell degranulation model, and a passive cutaneous anaphylaxis (PCA) mice model, and the structure changes were detected by circular dichroism (CD) spectra and ultraviolet (UV) spectra. The results showed that the processed egg proteins were more readily digested compared to raw egg proteins. The serological experiments revealed a significant reduction in immunoglobulin E binding of egg proteins after thermal treatments (p < 0.05), particularly after frying. Subsequently, the RBL-2H3 cell degranulation experiment demonstrated a marked decrease in the level of egg allergens-induced ß-hexosaminidase release after cooking (p < 0.05). Moreover, the results from the PCA mice model indicated that the increase in vascular permeability was effectively relieved in the treated groups, especially in frying group (p < 0.05). Additionally, the α-helix and ß-turn contents of processed egg proteins were significantly decreased (p < 0.05) compared with native egg proteins. The UV spectra findings showed that all cooking treatments caused significant alterations in the tertiary structure, and fluorescence analysis indicated that cooking decreased the surface hydrophobicity of egg proteins. In conclusion, four traditional cooking methods reduced the allergenicity of egg proteins, particularly frying, and this reduction was associated with structural changes that could contribute to the destruction or masking of epitopes of egg allergens. PRACTICAL APPLICATION: Egg allergy has a serious impact on public health, and there is no ideal treatment method at present. This study demonstrated that four traditional cooking methods (boiling, steaming, baking, and frying) reduced the allergenicity of egg proteins, especially frying, and the results will provide a basis for the development of hypoallergenic egg products.

Dietary Advancement Therapy Using Milk and Egg Ladders Among Children With a History of Anaphylaxis.

BACKGROUND: Anaphylaxis has been increasing in recent years, with common triggers in infants being milk and eggs. Currently, the mainstay of treatment for milk and/or egg allergy is strict avoidance. Recently, new therapies have emerged including stepwise introduction of allergens via a ladder approach. The suitability of infants for the ladders is debated. OBJECTIVE: This study aims to focus on the use of food ladders in children with anaphylaxis to egg or milk. METHODS: Retrospective review of pediatric patients diagnosed with immunoglobulin E-mediated milk and/or egg allergy between 2011 and 2021. Inclusion and exclusion criteria were applied. Anaphylaxis was defined as per the World Allergy Organization-amended criteria 2020. Data analysis utilized SPSS Version 28. RESULTS: We reviewed 1,552 patient charts, and excluded 1,094, leaving a total sample size of 458. Seventy infants had anaphylaxis at diagnosis (milk n = 36; egg n = 34). A range of 77.8% to 85.2% of infants with anaphylaxis successfully completed the ladder, 88.9% to 92.9% without anaphylaxis were successful. Children who successfully completed the ladder did so at similar rates. A range of 20.6% to 50% children presenting with anaphylaxis at diagnosis experienced allergic symptoms during treatment, compared with 17.3% to 40.7% without anaphylaxis. Reactions were mild, mostly cutaneous and not requiring medical attention. Patients experiencing allergic symptoms while on the ladder were less likely to successfully complete treatment. CONCLUSIONS: Milk and egg ladders are a safe and effective way of inducing tolerance in infants, including those with a history of anaphylaxis at diagnosis. There are no obvious predictors for who will experience allergic reactions while on the ladder; however, these children are less likely to complete the ladder, so parents should be educated in management of mild allergic reactions at home.

The age-specific microbiome of children with milk, egg, and peanut allergy.

BACKGROUND: Immune regulation by gut microbiota is affected by dysbiosis and may precede food allergy onset. Prior studies lacked comparisons stratified by age and clinical phenotype. OBJECTIVE: To assess the microbiome of children with food allergy (<3 years, 3-18 years) compared with similar aged children without food allergy. METHODS: A real-world prospective cross-sectional study performed from 2014 to 2019 recruited children highly likely to have milk, egg, or peanut allergy defined by history and serum IgE or confirmed by food challenge. 16S ribosomal RNA sequencing identified stool microbial DNA. Alpha and beta diversity was compared between groups with food allergy and healthy controls stratified by age. Differential abundance for non a priori taxa was accepted at absolute fold-change greater than 2 and q value less than 0.05. RESULTS: A total of 70 patients were included (56 with food allergy and 14 healthy controls). Groups were not significantly different in age, gender at birth, race, mode of delivery, breastfeeding duration, or antibiotic exposure. Younger children with food allergy had similar alpha diversity compared with controls. Beta diversity was significantly different by age (P = .001). There was differential abundance of several a priori (P < .05) taxa (including Clostridia) only in younger children. Both a priori (including Coprococcus and Clostridia) and non a priori (q < 0.05) Acidobacteria_Gp15, Aestuariispira, Tindallia, and Desulfitispora were significant in older children with food allergy, especially with peanut allergy. CONCLUSION: Dysbiosis associates with food allergy, most prominent in older children with peanut allergy. Younger children with and without food allergy have fewer differences in gut microbiota. This correlates with clinical observations of persistence of peanut allergy and improved efficacy and safety of oral immunotherapy in younger children. Age younger than 3 years should be considered when initiating therapeutic interventions.

Design of the Intervention to Reduce Early Peanut Allergy in Children (iREACH): A practice-based clinical trial.

BACKGROUND: Introducing peanut products early can prevent peanut allergy (PA). The "Addendum guidelines for the prevention of PA in the United States" (PPA guidelines) recommend early introduction of peanut products to low and moderate risk infants and evaluation prior to starting peanut products for infants at high risk for PA (those with severe eczema and/or egg allergy). Rapid adoption of guidelines could aid in lowering the prevalence of PA. The Intervention to Reduce Early (Peanut) Allergy in Children (iREACH) trial was designed to promote PPA guideline adherence by pediatric clinicians. METHODS: A two-arm, cluster-randomized, controlled clinical trial was designed to measure the effectiveness of an intervention that included clinician education and accompanying clinical decision support tools integrated in electronic health records (EHR) versus standard care. Randomization was at the practice level (n = 30). Primary aims evaluated over an 18-month trial period assess adherence to the PPA guidelines using EHR documentation at 4- and 6-month well-child care visits aided by natural language processing. A secondary aim will evaluate the effectiveness in decreasing the incidence of PA by age 2.5 years using EHR documentation and caregiver surveys. The unit of observation for evaluations are individual children with clustering at the practice level. CONCLUSION: Application of this intervention has the potential to inform the development of strategies to speed implementation of PPA guidelines.

Food Matrix Composition Affects the Allergenicity of Baked Egg Products.

BACKGROUND: Egg allergy is common and caused by sensitization to ovomucoid and/or ovalbumin. Many egg-allergic patients are able to tolerate eggs baked into other foods, such as muffins. Although heating egg extensively reduces allergens, the effect of other food ingredients on allergenicity of eggs, or the "matrix effect," is less well studied. OBJECTIVE: We aimed to define how food matrices impact the matrix effect in egg allergenicity. METHODS: Enzyme-linked immunosorbent assay was used to quantify ovalbumin and ovomucoid in extracts from various baked egg products: plain baked egg without a matrix, and muffins baked using either wheat flour, rice flour, or a wheat flour/banana puree mix. Allergen-specific immunoglobulin E (IgE)-blocking enzyme-linked immunosorbent assays were performed using the egg product extracts on egg-allergic patient sera to determine whether the amount of extracted egg protein in each extract correlated with how well the extracts could bind patients' egg IgE. RESULTS: Baking eggs in any muffin matrix led to an increase in the amount of extractable ovalbumin and a decrease in the amount of extractable ovomucoid compared with plain baked egg. Compared with wheat muffins, rice muffins had more extractable ovalbumin and wheat/banana muffins had more extractable ovalbumin and ovomucoid. The egg allergens in the extracts were able to block egg-allergic patients' egg IgE. CONCLUSIONS: Food matrices affect egg allergen availability. Patients and families should be advised that substitutions in baked egg muffin recipes can affect the amount of egg allergens in foods and potentially affect the risk of food allergic reaction.

Oral administration of egg ovalbumin allergen induces dysregulation of tryptophan metabolism in sensitized BALB/c mice.

Food allergy (FA), triggered by specific dietary allergens, has emerged as a substantial global concern for food safety and public health. While studies have elucidated changes in immune cells and cytokines associated with allergen exposure, a comprehensive analysis of the host's metabolic features and the interaction between metabolites and the gut microbiota has not been conducted. In this study, egg allergen ovalbumin (OVA) was administered by the oral route to sensitized BALB/c mice to faithfully replicate key aspects of human FA, including severe allergic diarrhea, mast cell infiltration, and elevated levels of serum IgE, mMCPT-1, and Th2 cell hallmark cytokines (such as IL-4, IL-5, and IL-13). Furthermore, the untargeted and targeted metabolomic analyses indicated that FA in mice precipitated a substantial decrease in the tryptophan metabolites indole-3-acrylic acid (IA) and indole-3-lactic acid (ILA). The integration of shotgun metagenome and metabolome data further unveiled that the dysregulation of indole metabolism is related to a decline in the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium. Additionally, disruption of the tryptophan indole derivative pathway compromises the maintenance of intestinal mucosal function through the AHR signaling pathway, manifested by decreased expression of Reg3g and IL22. Taken together, this study demonstrated that the anaphylaxis triggered by oral ingestion of food allergens can lead to disruptions in tryptophan metabolism, consequently impairing intestinal immune homeostasis.

A rare case of lysozyme-induced anaphylaxis in a child with egg allergy.

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions.

Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

PURPOSE OF REVIEW: Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. RECENT FINDINGS: Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. SUMMARY: Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.

Clinical characteristics and management of pediatric egg-induced anaphylaxis: A cross-sectional study.

BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.

Variation in the Allergenicity of Scrambled, Boiled, Short-Baked and Long-Baked Egg White Proteins.

BACKGROUND: Hen's egg white (HEW) is the most common cause of food allergy in children which induces mild to fatal reactions. The consultation for a proper restriction is important in HEW allergy. We aimed to identify the changes in HEW allergenicity using diverse cooking methods commonly used in Korean dishes. METHODS: Crude extract of raw and 4 types of cooked HEW extracts were produced and used for sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), enzyme-linked immunosorbent assay (ELISA), and ELISA inhibition assays using 45 serum samples from HEW allergic and tolerant children. Extracts were prepared; scrambled without oil for 20-30 seconds in frying pan without oil, boiled at 100°C for 15 minutes, short-baked at 180°C for 20 minutes, and long-baked at 45°C for 12 hours with a gradual increase in temperature up to 110°C for additional 12 hours, respectively. RESULTS: In SDS-PAGE, the intensity of bands of 50-54 kDa decreased by boiling and baking. All bands almost disappeared in long-baked eggs. The intensity of the ovalbumin (OVA) immunoglobulin E (IgE) bands did not change after scrambling; however, an evident decrease was observed in boiled egg white (EW). In contrast, ovomucoid (OM) IgE bands were darker and wider after scrambling and boiling. The IgE binding reactivity to all EW allergens were weakened in short-baked EW and considerably diminished in long-baked EW. In individual ELISA analysis using OVA+OM+ serum samples, the median of specific IgE optical density values was 0.435 in raw EW, 0.476 in scrambled EW, and 0.487 in boiled EW. Conversely, it was significantly decreased in short-baked (0.406) and long-baked EW (0.012). Significant inhibition was observed by four inhibitors such as raw, scrambled, boiled and short-baked HEW, but there was no significant inhibition by long-baked HEW (IC50 > 100 mg/mL). CONCLUSION: We identified minimally reduced allergenicity in scrambled EW and extensively decreased allergenicity in long-baked EW comparing to boiled and short-baked EW as well as raw EW. By applying the results of this study, we would be able to provide safer dietary guidence with higher quality to egg allergic children.

Clinical outcome and component-specific antibody levels in egg allergic children after lightened oral immunotherapy

Objective: To evaluate the clinical outcome of lightened version of egg oral immunotherapy (OIT) and to analyze egg allergen component-specific antibody levels during short up-dosing with egg white powder and maintenance by egg in daily diet. Patients and methods: Eighteen egg-allergic children received egg powder with short up--dosing and they maintained tolerance using egg in daily diet. Seventeen egg-allergic children served as a control group. Component-resolved analysis of serum immunoglobulin E (IgE), IgA1, IgA2, and IgG4 levels were determined at inclusion, after up-dosing and after 1 year of immunotherapy. Skin-prick tests were performed at inclusion and after 1 year of therapy. Results: All 18 patients in the egg OIT group were successfully desensitized. Desensitization was achieved on average in 4.5 months. In the control group, only two children tolerated egg in oral food challenge after 1 year. Of the measured immune markers, smaller wheal diameters in skin-prick testing, reduction in component-specific IgE levels, and increase in component-specific IgA1, IgA2, and IgG4 levels were associated with desensitization. Conclusion: A lightened egg OIT is effective and safe in children with egg allergy. Increase in all egg component-specific IgA1, IgA2 and IgG4 levels and decrease in all egg component--specific IgE levels were observed after 12 months of OIT (AU)

Basophil activation test as predictor of severity and threshold of allergic reactions to egg.

BACKGROUND: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg. METHODS: One hundred and fifty children underwent double-blind placebo-controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC. Severity of allergic reactions was classified following Practall guidelines and threshold dose was determined during DBPCFC. RESULTS: Sixty out of 150 (40%) children reacted to BE and 16 out of 77 (21%) to LCE on DBPCFC. Considering DBPCFC to BE, 23 children (38%) had severe reactions and 33 (55%) reacted to 0.13 g or less of egg protein (low threshold group). Two children (2 out of 16 = 12%) had severe reactions to LCE. Demographic, clinical and most immunological features were not significantly different between severe/non-severe BE reactors or low/high threshold groups. Severe BE reactors had higher ovomucoid-sIgE (p = .009) and higher BAT to BE (p = .001). Patients with lower threshold to BE had higher IgE-specific activity (p = .027) and BAT to egg (p = .007) but lower severity score (p = .008). Optimal cut-offs for ovomucoid-sIgE had 100% sensitivity, 35% specificity and 60% accuracy and for BAT 76% sensitivity, 74% specificity and 75% accuracy to identify BE severe reactors. Optimal cut-offs for specific activity had 70% sensitivity, 68% specificity and 69% accuracy and for BAT 70% sensitivity, 72% specificity and 71% accuracy to identify low threshold patients. CONCLUSIONS: BAT was the best biomarker to predict severity and threshold of allergic reactions to BE and can be useful when making decisions about management of egg allergy.