BackgroundOral immunotherapy (OIT) is a promising approach for treating IgE‐mediated food allergy, but safety concerns limit its use. Heat‐denaturation of food allergens may reduce allergic reactions by lowering IgE binding. Here, we examined how heat‐induced structural changes in egg allergens affected basophil activation in egg‐allergic patients.MethodsGal d 1 and Gal d 2 were subjected to heat treatment and analyzed for structural changes using SDS‐PAGE, ELISA, NanoDSF, and circular dichroism. Peripheral blood samples were obtained from a cohort of 42 patients with egg allergy. Patients' sensitization status was determined, and basophils were isolated and incubated with native or heat‐denatured egg allergen preparations. Basophil activation was assessed by measuring leukotriene release as a marker of degranulation.ResultsHeat‐denaturation induced time‐ and temperature‐dependent structural changes in both Gal d 1 and Gal d 2, resulting in reduced IgE binding capacity. In functional assays, heat‐denatured allergens elicited weaker basophil degranulation responses compared to native allergens, but the effect varied depending on individual IgE sensitization profiles. Among patients who reacted to heat‐denatured allergens, egg‐white IgE levels tended to be higher, although requiring higher doses to trigger leukotriene release.ConclusionHeat‐denaturation of egg allergens reduces IgE‐binding and basophil activation, although residual reactivity persists in patients with higher sensitization profiles. Importantly, higher allergen doses were needed to trigger basophil degranulation compared to native allergens, indicating a reduction in allergenic potency. These findings highlight the potential of heat‐denatured egg allergens as safer starting materials for OIT, particularly within personalized, stepwise desensitization protocols, warranting further clinical investigation.

IntroductionX‐linked inhibitor of apoptosis protein (XIAP) deficiency is an inborn error of immunity caused by pathogenic variants of XIAP. It presents diverse symptoms, including recurrent hemophagocytic lymphohistiocytosis and inflammatory bowel disease. Previous reports established a functional analysis method that quantitatively evaluates intracellular tumor necrosis factor‐alpha (TNF‐α) production capacity following muramyl dipeptide (MDP) stimulation using flow cytometry (MDP‐flow TNF‐α) for assessing XIAP deficiency. However, this method required 2 days to obtain results, which is a limitation.MethodWe established a method to measure the downregulation of L‐selectin (CD62L) on the cell surface after MDP stimulation of monocytes and neutrophils from patients with XIAP deficiency using flow cytometry (MDP‐flow CD62L) within 4 h. Moreover, we also evaluated MDP‐flow CD62L in patients with XIAP deficiency after allogeneic hematopoietic cell transplantation (HCT) to evaluate its usefulness in functional analysis.ResultsSix patients with XIAP variants, two with interleukin‐1 receptor‐associated kinase 4 deficiency, and healthy controls were analyzed. The mean percent inhibition of CD62L expression (%inhibition) was evaluated in monocytes and neutrophils. The mean inhibition rates of CD62L expression in monocytes and neutrophils from patients with XIAP deficiency were 5.96% and 6.20%, respectively, significantly lower than those from healthy controls (monocytes, 85.4%; neutrophils, 85.4%). Furthermore, in three patients with XIAP deficiency after HCT, the MDP‐flow CD62L was evaluated post‐HCT, confirming improvement in accordance with donor chimerism.ConclusionIn XIAP deficiency, MDP‐flow CD62L enabled faster functional analysis than MDP‐flow TNF‐α. These analyses are also useful for post‐HCT functional assessment.

BackgroundBiologics have been shown to substantially reduce the risk of severe asthma exacerbations (SAEs) among children with moderate or severe asthma; however, not all eligible patients who initiate biologic treatment experience a reduced risk of SAEs.MethodsUsing a longitudinal study design, we analyzed data from 122 children with moderate/severe asthma treated with a biologic by pediatric subspecialists between December 2019 and December 2024. We used logistic and Cox proportional hazards models to identify and quantify the prognostic utility of clinical correlates of increased SAE risk among children with moderate or severe asthma prior to biologic treatment initiation.ResultsBiologic agents (dupilumab, omalizumab, and mepolizumab) had differential effects on the risk of SAE depending on a child's sex (p = .024), age of treatment initiation (p = .010), lung function (% FEF25‐75 predicted: p = .034), and absolute neutrophils (p = .055). Dupilumab was associated with a higher risk of SAE among female patients. Omalizumab and mepolizumab were associated with a higher risk of SAEs among patients with elevated absolute neutrophils and younger age at treatment initiation. Consideration of these clinical parameters in a multivariable model improved the pre‐treatment prognostic accuracy of SAE risk by 23% compared to reliance on history of SAEs alone (0.86; 95% CI: 0.79, 0.89 vs. 0.63; 95% CI: 0.54, 0.72).ConclusionBeyond biologic treatment eligibility, using routinely collected clinical parameters to stratify pre‐treatment SAE risk could improve prognostic accuracy and aid clinicians in tailoring therapy based on a patient's individual risk factors and likelihood of responding to a specific agent to maximize treatment effectiveness.

BackgroundNon‐priority legume (NPL) allergies are increasing, creating significant concerns due to the widespread use of these foods. This study aims to evaluate the natural history of NPL allergy in children and identify predictive factors associated with their resolution.MethodsA retrospective review of medical records of pediatric patients (Age 5–15 Years) from the Pediatric Allergy Department at Evelina London Children's Hospital (from July 2023 to June 2024) who had an IgE‐mediated allergy to any NPLs (lentils, chickpeas, peas, and beans). Children with a suggestive history of NPL allergy with a positive skin prick test (SPT) ≥8 Mm, specific immunoglobulin E (sIgE) ≥15 kUA/L and/or positive oral food challenge were included.ResultsTwo hundred and three children were included; the median age was 10 years (62.6% male), and median duration of follow‐up was 7 years. 6.3% of all children with food allergies were allergic to NPLs, with lentils being most common. Kaplan–Meier analysis showed varying resolution rates by age: 2.2% for lentils, 4.9% for chickpeas, 8.3% for peas, and 13% for beans by age 5. By age 10, these rates increased to 11.3%, 8.8%, 20.1%, and 24.5%, respectively, and by age 15, they increased to 21% for lentils, 19.3% for chickpeas, 23.5% for peas, and 32.9% for beans. Children who had low SPT and sIgE results were more likely to outgrow their legume allergy.ConclusionNPL allergy represents a significant disease burden and the rate of resolution by age 15 years was 20%–32.9%, similar to legumes such as peanut.

BackgroundPediatric atopic dermatitis exhibits substantial heterogeneity in presentation, course, and long‐term outcomes resulting in distinct phenotypes. Yet, genetic studies of atopic dermatitis have focused on a single trait or outcome and thus may not fully reveal underlying genetic relationships.ObjectiveTo identify novel genetic associations with early‐life atopic dermatitis traits and evaluate shared genetic architecture across heterogeneous quantitative outcomes using a genome‐wide cross‐trait approach.MethodsChildren (n = 601) participating in the Mechanisms in the Progression of Atopic Dermatitis to Asthma in Childhood were genotyped and association was performed for each of 12 traits. Pleiotropy analyses were used to organize genetically similar traits into Pleiotropic Groups. A principal components (composite) variable was generated for each pleiotropic group and another genetic association was performed.ResultsFive novel genome‐wide significant associations were identified with single traits: progression to additional atopic conditions, S100A8 lesional expression (2 associations), sensitization to food allergens, and sensitization to aeroallergens. When evaluating pleiotropy, the 12 traits organized into 4 pleiotropic groups. There were more shared gene associations among traits within a pleiotropic group than between (p = 1.5 × 10−5). A novel genome‐wide significant association was found with the Composite Variable from Pleiotropic Group 3.ConclusionHerein, we identify novel genetic associations with pediatric atopic dermatitis traits. Further, our findings reveal a novel opportunity for enhancing genetic discovery by leveraging multi‐trait effects and provide new insights into atopic dermatitis traits with shared genetic etiologies.