Autoclaved Peanuts Exhibit Reduced Immunoglobulin E Binding and Improved Oral Tolerability
Background: Major peanut allergens are stable and resistant to denaturation under standard cooking conditions, contributing to allergenicity and low rates of developing natural tolerance in allergic individuals. We evaluated the effects of heat and pressure autoclaving on peanut proteins, IgE binding, and oral tolerability. Methods: Raw, roasted, and autoclaved peanut protein extracts were evaluated by Bradford assay, ELISA, and mass spectrometry-proteomics to compare relative amounts of protein, specific IgE binding, and allergen fragmentation. To assess changes in clinical reactivity, we performed skin prick testing (SPT) in 41 subjects using standard and autoclaved peanut extracts. We also performed double-blind oral food challenges (OFC) in 10 peanut-allergic subjects with standard and autoclaved peanuts. Results: Autoclaving at 130°C, 2.4 atm, for 30 min significantly degraded allergens Ara h 1 and 2, and completely degraded Ara h 8. Mass spectrometry-proteomics analysis of size-filtered extracts (< 10 kDa) showed greater numbers and diversity of peptides from peanut proteins and allergens in autoclaved extracts. Autoclaving fragmented proteins into shorter peptides, against which sera from highly allergic patients exhibited a 74% reduction in IgE binding compared to raw peanuts. SPT demonstrated significant decreases in wheal diameters using autoclaved peanut extract (median [IQR] = 5 mm [2, 9]) compared to commercial extract (10 mm [6, 15]; p < 0.001). All OFC subjects tolerated the maximum cumulative autoclaved peanut dose (444 mg) versus standard peanut (median: 9 mg, range: [1, 44]). Conclusions: Autoclaving peanuts induces important chemical changes including fragmentation, leading to decreased peanut allergenicity and consequently increased tolerability. This has the potential for novel immunotherapeutic approaches with more favorable side effect profiles.
https://doi.org/10.1111/all.70208
Guidelines for Early Food Introduction and Patterns of Food Allergy
Objective: We aimed to determine whether rates of peanut (or any) immunoglobulin E-mediated food allergy (IgE-FA) changed following the publication of early peanut introduction guidelines and/or addendum guidelines. Methods: Using electronic health record data from the multistate, primary care-based American Academy of Pediatrics Comparative Effectiveness Research through Collaborative Electronic Reporting (CER2) network, we defined preguidelines, postguidelines, and postaddendum guidelines cohorts (cohort entry during September 1, 2012, to August 31, 2014; September 1, 2015, to August 31, 2017; and February 1, 2017, to January 31, 2019, respectively). We determined the cumulative incidence of IgE-FA and/or atopic dermatitis (AD) in children aged 0-3 years, observed for either at least 1 or 2 years. Diagnosis rates during pre- vs postguidelines periods were compared using logistic regression, Cox proportional hazards modeling, and interrupted time series analysis. Results: The cumulative incidence and risk of development of peanut IgE-FA (0.79%-0.53%; hazard ratio [HR], 0.65; 95% CI, 0.55-0.77) and any IgE-FA (1.46%-1.02%; HR, 0.69; 95% CI, 0.61-0.78) decreased significantly (P < .0001) from the preguidelines to postguidelines period. Furthermore, the cumulative incidence and risk of development of peanut IgE-FA (0.79%-0.45%; HR, 0.55; 95% CI, 0.46-0.66) and any IgE-FA (1.46%-0.93%; HR, 0.63; 95% CI, 0.55-0.72) decreased significantly (P < .0001) from the preguidelines to postaddendum guidelines period. A decline in IgE-FA diagnosis postguidelines was confirmed in the interrupted time series analysis. Conclusion: We detected decreased rates of peanut or any IgE-FA in the period following the publication of early introduction guidelines and addendum guidelines. Our results are supportive of the intended effect of these landmark public health recommendations.
https://doi.org/10.1542/peds.2024-070516
Mixed Nut Challenge Test (MixNut) as an Efficient Procedure in the Management of Lipid Transfer Protein Allergy
Background/Objectives: Lipid transfer protein (LTP) syndrome is a leading cause of primary food allergy in Mediterranean countries, often associated with severe reactions. Due to in vitro cross-reactivity among plant foods, clinical manifestations are unpredictable, frequently requiring multiple oral food challenges (OFC) to assess nut tolerance. These procedures increase healthcare burden and patient anxiety. This study evaluated the safety and utility of a mixed-nut oral food challenge (MixNut) in LTP-sensitized patients. Methods: In this prospective observational multi-center study, patients with LTP syndrome were enrolled. Group A included individuals allergic to fruits or vegetables who had avoided nuts; Group B included patients with suspected or confirmed nut allergy. Participants underwent a MixNut challenge comprising 2–4 nuts (≥3 g protein per nut). Results: Nineteen patients (73.7% male; median age 32.5 years) underwent MixNut, testing 52 individual nuts. All challenges were negative. The MixNut approach reduced the number of OFC by 63% (from 52 to 19) and total testing time from 208 to 76 h. Specific IgE levels to LTP allergens (Pru p 3, Cor a 8, Ara h 9) varied widely and did not predict clinical reactivity. Conclusions: MixNut is an efficient diagnostic tool for LTP syndrome, significantly reducing testing time, costs, and patient burden. It facilitates accurate dietary management and prevents unnecessary food avoidance. Further studies should optimize MixNut protocols and identify predictive markers for clinical reactivity.
https://doi.org/10.3390/nu17243822
Trends over a decade in the prevalence and eliciting dose of peanut and tree nut allergies in Japan
Background: The prevalence of tree nuts allergy is rapidly increasing in Japan, yet the eliciting dose (ED) for tree nuts, particularly in Asian populations, has not been sufficiently investigated. Objective: This study aimed to quantify EDs for peanut, cashew nut, and walnut in Japanese patients with food allergies and to investigate longitudinal changes in these values. Methods: We retrospectively analyzed 1,275 oral food challenge results for patients with diagnosed peanut, cashew nut, or walnut allergy, conducted between November 2013 and December 2023 at a single allergy center. EDs were calculated using the Weibull, log-normal, and log-logistic models, and bivariate survival analysis was used to examine the relationship between allergen-specific IgE levels and ED causing reaction in 5% of the allergic population (ED05). Results: The ED05 values were determined as 4.88 mg for peanut, 0.53 mg for cashew nut, and 4.37 mg for walnut. When the component-specific IgE was set at 50.0 kUA/L, ED05 decreased to 3.20 mg, 0.55 mg, and 1.92 mg, respectively. Notably, a marked decline in walnut ED was observed over time. Conclusions: EDs in Japanese tree nut-allergic populations are decreasingly aligned with those reported in Western countries, reflecting shifts in dietary habits and allergen exposure. The findings of the dynamic nature of threshold dose distributions over time, even within the same region, emphasize the necessity for periodic reassessment of allergen risk thresholds to ensure optimal patient safety.
https://doi.org/10.1016/j.jacig.2025.100582
Guidelines for Early Food Introduction and Patterns of Food Allergy
Objective: We aimed to determine whether rates of peanut (or any) immunoglobulin E-mediated food allergy (IgE-FA) changed following the publication of early peanut introduction guidelines and/or addendum guidelines. Methods: Using electronic health record data from the multistate, primary care-based American Academy of Pediatrics Comparative Effectiveness Research through Collaborative Electronic Reporting (CER2) network, we defined preguidelines, postguidelines, and postaddendum guidelines cohorts (cohort entry during September 1, 2012, to August 31, 2014; September 1, 2015, to August 31, 2017; and February 1, 2017, to January 31, 2019, respectively). We determined the cumulative incidence of IgE-FA and/or atopic dermatitis (AD) in children aged 0-3 years, observed for either at least 1 or 2 years. Diagnosis rates during pre- vs postguidelines periods were compared using logistic regression, Cox proportional hazards modeling, and interrupted time series analysis. Results: The cumulative incidence and risk of development of peanut IgE-FA (0.79%-0.53%; hazard ratio [HR], 0.65; 95% CI, 0.55-0.77) and any IgE-FA (1.46%-1.02%; HR, 0.69; 95% CI, 0.61-0.78) decreased significantly (P < .0001) from the preguidelines to postguidelines period. Furthermore, the cumulative incidence and risk of development of peanut IgE-FA (0.79%-0.45%; HR, 0.55; 95% CI, 0.46-0.66) and any IgE-FA (1.46%-0.93%; HR, 0.63; 95% CI, 0.55-0.72) decreased significantly (P < .0001) from the preguidelines to postaddendum guidelines period. A decline in IgE-FA diagnosis postguidelines was confirmed in the interrupted time series analysis. Conclusion: We detected decreased rates of peanut or any IgE-FA in the period following the publication of early introduction guidelines and addendum guidelines. Our results are supportive of the intended effect of these landmark public health recommendations.
https://doi.org/10.1542/peds.2024-070516
From Sensitisation to Tolerance: A Retrospective Study of Tree Nut and Peanut Allergy in Pediatric Patients
Background: Tree nut/Peanut (TN/PN) allergies are among the most common pediatric food allergies, often persisting into later life and posing significant clinical risks. The likelihood of tolerance acquisition varies, and predictive factors remain inadequately defined in clinical practice. Objective: To evaluate the clinical and laboratory features associated with anaphylaxis risk and tolerance development in pediatric patients with TN/PN allergy, and to determine the role of aeroallergen sensitization, comorbid atopic diseases, and skin test reactivity. Methods: In this retrospective, cross-sectional study, 121 children (0-18 years) diagnosed with TN/PN allergy at a tertiary allergy centre between 2016 and 2024 were analyzed. Data included allergic reaction history, comorbidities, total IgE, eosinophil counts, and prick-to-prick (PTP) test wheal sizes. Tolerance acquisition was defined based on oral food challenge, absence of reactions upon re-exposure, and clinical follow-up. Results: Multiple nut allergy was present in 81% of patients, with hazelnut (67%) and pistachio (62%) being most common. IgE-mediated reactions were predominant (91%), including urticaria (79%) and anaphylaxis (36%). During follow-up, 25% of patients developed tolerance, while 13% continued to experience anaphylaxis. Aeroallergen sensitisation, particularly to pollens, was significantly associated with reduced tolerance in almond and walnut allergy (p < 0.05). Persistent multi-nut allergy correlated with higher anaphylaxis risk (p < 0.01). Strong co-sensitisation was observed between pistachio-cashew (r = 0.686) and almond-walnut (r = 0.579). Notably, smaller PTP wheal sizes predicted tolerance acquisition (p < 0.05). Conclusion: Pediatric TN/PN allergy is frequently severe and persistent. Multiple nut allergy, aeroallergen sensitization, and larger PTP wheal sizes are significant risk factors for prolonged allergy and anaphylaxis. Early identification of these markers may improve risk stratification and guide individualized follow-up strategies.
https://doi.org/10.1159/000548420
Pediatric food allergy prevalence and trends by race and ethnicity
Background: In the United States, food allergies (FAs) disproportionately affect children based on their racial or ethnic heritage, though there are some gaps and discrepancies in the literature about the prevalence of FAs among different groups. Objective: The objective was to analyze clinical data to determine how FA prevalence varies based on race and ethnicity and to track FA diagnosis rates over time. Methods: Patient FA diagnoses, birth years, and self-reported races or ethnicities were analyzed for 298,476 pediatric patients in the Children's Hospital of Philadelphia network. Odds ratios (OR) for FA were calculated for each race or ethnicity, controlling for sex, insurance type, and birth year. The percentages having each of the top 9 FAs and ORs for being allergic to a particular allergen and multiple allergens were calculated for each race or ethnicity using a subset of data for 20,582 food-allergic children. The percentages of each birth cohort diagnosed with FA were plotted. Results: Asian/Pacific Islander (A/PI) children had the highest odds of FA (OR, 1.92; CI, 1.80-2.05) and multiple FAs (OR, 1.55; CI, 1.37-1.76). The most common allergens varied between groups. All groups had higher odds than White children of allergies to fish and shellfish, but only A/PI children also had higher odds of peanut, egg, wheat, and sesame allergies. FA diagnoses appeared to increase until the 2004 birth cohort and remain steady through the 2008 birth cohort. Conclusions: Clinicians, researchers, and outreach coordinators should be aware of the potential for a significantly greater risk of FA for children of A/PI heritage in the United States. Additional studies that intentionally include patients from these demographics and monitor FA trends over time are warranted.
https://doi.org/10.5415/apallergy.0000000000000189
Kinetics of early peanut allergy development and resolution in the EAT, LEAP, and PAS cohorts
Background: Little is known about the development and resolution of early peanut allergy (PA). Objective: We examined the natural history and biomarkers of PA longitudinally in 3 cohorts. Methods: PA development was examined in the Enquiring About Tolerance (EAT), Learning Early About Peanut (LEAP), and Peanut Allergy Sensitization (PAS) cohorts. Early PA was defined by skin prick test result of >4 mm by 12 months or oral food challenge at study entry. PA was confirmed by oral food challenge at study end point (36 months for EAT, 60 months for LEAP/PAS). Four groups were defined: early PA development with persistence (EP); early PA development with resolution (ER); late PA development (LA); and never peanut allergic. Clinical characteristics and biomarkers were compared between the groups. Results: A total of 56.3% of peanut-allergic children developed PA by 12 months; 32.1% had early PA resolution by study end point. The rate of early PA resolution was 54.2% in EAT, 41.4% in LEAP, and 18.6% in PAS cohorts. Median skin prick test wheals for EP, ER, and LA were 6, 2, and 0 mm at baseline, and 10, 0, 9 mm at study end point. Median peanut-specific IgE (sIgE) levels for EP, ER, and LA were 5.9, 0.4, and 0.3 kUA/L (P < .001) at baseline; 4.7, 1.3, and 0.9 kUA/L (P < .001) at 12 months; and 20.1, 0.2, and 5.1 kUA/L (P < .001) at study end point. LA had slower component expansion (number of components Ara h 1-sIgE, Ara h 2-sIgE, Ara h 3-sIgE > 0.1 kUA/L) compared to EP. ER showed component expansion from baseline to 12 months but component retraction by study end point. Absence of eczema and egg allergy, low peanut-sIgE, or skin prick test result were predictive of PA resolution. Conclusion: A significant proportion of PA resolves in early childhood. Different phenotypes of PA display different biomarkers trajectories.
https://doi.org/10.1016/j.jaci.2024.10.042
Infant Diet Recommendations Reduce IgE-Mediated Egg, Peanut, and Cow's Milk Allergies
Background: Meta-analyses of randomized controlled trials have found that introducing eggs and peanuts earlier during infancy reduced egg and peanut allergy risk. Hence, infant feeding advice has dramatically changed from previous recommendations of avoidance to current recommendations of inclusion of common food allergens in infant diets. Objective: To compare the prevalence of IgE-mediated food allergies at 1 year of age between 2 cohorts, before and after infant feeding and allergy prevention guidelines changed. Methods: In cohort 1 (506 infants born 2006-2014), no infant feeding advice was provided to participants. In cohort 2 (566 infants born 2016-2022), when the infants were 6 months of age, all families were provided with updated infant feeding and allergy prevention guidelines. All infants had a first-degree relative with a history of allergic disease. At 1 year of age, infant food allergen sensitization and IgE-mediated food allergy were assessed. Results: Peanut, egg, and cow's milk were introduced earlier in cohort 2 than in cohort 1 (all P < .001). The combined prevalence of IgE-mediated peanut, egg, and/or cow's milk allergies was 4.1% in cohort 2 compared with 12.6% in cohort 1 (adjusted odds ratio [aOR]: 0.28, 95% confidence interval [CI]: 0.16-0.48, P < .001). Specifically, the prevalence of peanut allergy was 1.1% versus 5.8% (aOR: 0.24, 95% CI: 0.08-0.76, P = .015), egg allergy 2.8% versus 11.7% (aOR: 0.23, 95% CI: 0.12-0.45, P < .001), and cow's milk allergy 0.5% versus 2.4%, respectively (aOR: 0.14, 95% CI: 0.04-0.55, P = .005). Conclusion: Direct provision of updated food allergy prevention guidelines to families facilitated earlier introduction and reduced the prevalence of IgE-mediated peanut, egg, and cow's milk allergies.
https://doi.org/10.1016/j.jaip.2025.06.012
Exploring quality of life and related clinical factors in children with tree nut allergies
Background: In Türkiye, tree nut allergy (TNA) is the most common form of food allergy, characterized by persistence and the potential for life-threatening reactions. This study aimed to evaluate the quality of life (QoL) of Turkish children aged 0-12 years with IgE-mediated TNA and explore influential factors, including parental anxiety. Materials and methods: Primary caregiver-parents of children diagnosed with TNA completed the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and State-Trait Anxiety Inventory (STAI) to assess QoL and parental anxiety, respectively. Results: Of 120 eligible patients diagnosed with TNA, 88 were included in the study. Questionnaires were completed by mothers in 79 cases (90%) and fathers in 9 cases (10%). Parents reported significantly higher FAQLQ-PF scores for children with hazelnut allergy, a history of anaphylaxis, and those who had to use an adrenaline auto-injector. There was significant but weak correlations between FAQLQ-PF and anxiety (STAI) domains. The multivariate linear regression analysis revealed that having a hazelnut allergy, a history of anaphylaxis, and higher parental state anxiety were all associated with higher FAQLQ-PF scores, but fathers tended to report better level of QoL. Conclusion: QoL for children with TNA is influenced by several factors such as adverse life experiences, local and situational factors, and parental anxiety. Understanding these diverse factors is crucial for enhancing the well-being of children with TNA.
https://doi.org/10.24953/turkjpediatr.2025.5293