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
A Growing Concern for Cashew and an Unexpected Risk From Almonds: Data From the Anaphylaxis Registry
Background: Food allergies are a major health concern with rising prevalence. Dietary habits are changing, and information about cashew-induced anaphylaxis is limited. Methods: Cases of tree nut-induced anaphylaxis (TIA) registered from 2007 until April 2024 were extracted from the European Anaphylaxis Registry and analyzed. Results: 1389 cases of TIA out of 5945 registered food-induced reactions (23%) were identified. 1,083 cases with confirmed elicitor status, including 845 children (median age 4 years, 61% male) and 238 adults (38 years, 40% male), were selected for further analysis. The most frequent elicitors among children were cashew (n = 334), hazelnut (n = 211) and walnut (n = 146). The proportion of cashew-induced anaphylaxis increased from 2007 to 2024, and reactions were frequently caused by small amounts (< 1 teaspoon). Adults reacted frequently to hazelnut (n = 105), walnut (n = 47) but also almond (n = 35) and to higher amounts. Potential cofactors were present in 50% of the adult patients and 17% of children. The reaction severity was age-independent, and only a minority of patients was previously aware of their allergy (children 23%, adults 21%). The use of adrenaline was low in lay treatment (children 13%, adults 3%) and reached approximately 40% upon professional treatment. Conclusion: Cashew is an increasing, relevant allergen leading to anaphylaxis and is now the most frequent cause of TIA among children. These findings highlight the need for effective prevention and treatment measures. Almond was a frequent elicitor among adults and should be further monitored. The acute management requires improvement to comply with current guidelines.
https://doi.org/10.1111/all.16619
Epicutaneous immunotherapy for the treatment of peanut allergy
Peanut allergy treatment options remain limited, but novel approaches are being studied, including epicutaneous immunotherapy (EPIT). EPIT uses the cutaneous immune system to promote tolerance to food allergens. Viaskin™ Peanut, an approach to EPIT in late-stage clinical development uses an occlusive patch with a condensation chamber that enables natural epidermal water loss to solubilize dry antigen on the patch, which is then absorbed and captured by skin Langerhans cells. This form of EPIT does not require disruption of the skin barrier, thus avoiding a proinflammatory cytokine response by targeting the nonvascularized epidermis and limiting systemic allergen exposure. Extensive preclinical research suggests that Viaskin Peanut has a distinct mechanism of desensitization, including the potential for disease modification, driven by a unique population of regulatory T cells. Numerous clinical studies of Viaskin Peanut have demonstrated desensitization and reductions in reaction severity, particularly in children aged 1 through 11 years, as well as a favorable safety profile with mostly mild-to-moderate skin reactions that were observed to decrease over time. EPIT with Viaskin Peanut may be a potential therapeutic option for peanut allergy that is clinically practical with long-term efficacy and tolerability. https://doi.org/10.1111/all.16324
Biomarkers of peanut allergy in children over time
Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point. Results: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time. Conclusions: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time. https://doi.org/10.1111/all.16193
Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis
In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.
https://doi.org/10.1111/all.15905
Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy
The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.
https://doi.org/10.1111/all.15939
Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy
Background: Food allergy is a leading cause of anaphylaxis worldwide. Allergen-specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short-lived efficacy. Allergen-derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T-cell epitopes of major peanut allergens for treatment of peanut allergy. Methods: Pre-clinical safety of PVX108 was assessed using ex vivo basophil activation tests (n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first-in-human, randomized, double-blind, placebo-controlled trial in peanut-allergic adults (46 active, 21 placebo). The repeat-dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre-dose, Week 21 and Month 18 after treatment. Results: PVX108 induced negligible activation of peanut-sensitised basophils. PVX108 was safe and well tolerated in peanut-allergic adults. There were no treatment-related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2+ Th2A:CCR6+ Th17-like cells within the peanut-reactive Th pool which strengthened following treatment. Conclusion: This study supports the concept that PVX108 could provide a safe alternative to whole peanut immunotherapies and provides evidence of durable peanut-specific T-cell modulation. Translation of these findings to clinical efficacy in ongoing Phase 2 trials would provide important proof-of-concept for using peptides to treat food allergy.
https://doi.org/10.1111/all.15966
EAACI guidelines on the diagnosis of IgE-mediated food allergy
This European Academy of Allergy and Clinical Immunology guideline provides recommendations for diagnosing IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Food allergy diagnosis starts with an allergy-focused clinical history followed by tests to determine IgE sensitization, such as serum allergen-specific IgE (sIgE) and skin prick test (SPT), and the basophil activation test (BAT), if available. Evidence for IgE sensitization should be sought for any suspected foods. The diagnosis of allergy to some foods, such as peanut and cashew nut, is well supported by SPT and serum sIgE, whereas there are less data and the performance of these tests is poorer for other foods, such as wheat and soya. The measurement of sIgE to allergen components such as Ara h 2 from peanut, Cor a 14 from hazelnut and Ana o 3 from cashew can be useful to further support the diagnosis, especially in pollen-sensitized individuals. BAT to peanut and sesame can be used additionally. The reference standard for food allergy diagnosis is the oral food challenge (OFC). OFC should be performed in equivocal cases. For practical reasons, open challenges are suitable in most cases. Reassessment of food allergic children with allergy tests and/or OFCs periodically over time will enable reintroduction of food into the diet in the case of spontaneous acquisition of oral tolerance.
https://doi.org/10.1111/all.15902
Prevalence of tree nut allergy in Europe: A systematic review and meta-analysis
In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions.
https://doi.org/10.1111/all.15905
Early introduction of peanut reduces peanut allergy across risk groups in pooled and causal inference analyses.
Background: The LEAP study has shown the effectiveness of early peanut introduction in prevention of peanut allergy (PA). In the EAT study, a statistically significant reduction in PA was present only in per-protocol (PP) analyses, which can be subject to bias. Objective: To combine individual-level data from the LEAP and EAT trials and provide robust evidence on the bias-corrected, causal effect of early peanut introduction. Method: As part of the European Union-funded iFAAM project, this pooled analysis of individual paediatric patient data combines and compares effectiveness and efficacy estimates of oral tolerance induction among different risk strata and analysis methods. Results: An intention-to-treat (ITT) analysis of pooled data showed a 75% reduction in PA (p<0.0001) among children randomized to consume peanut from early infancy. A protective effect was present across all eczema severity groups, irrespective of enrolment sensitization to peanut, and across different ethnicities. Earlier age of introduction was associated with improved effectiveness of the intervention. In the pooled PP analysis, peanut consumption reduced the risk of PA by 98% (p<0.0001). A causal inference analysis confirmed the strong PP effect (89% average treatment effect relative risk reduction p<0.0001). A multivariable causal inference analysis approach estimated a large (100%) reduction in PA in children without eczema (p=0.004). Conclusion: We demonstrate a significant reduction in PA with early peanut introduction in a large group of pooled, randomized participants. This significant reduction was demonstrated across all risk subgroups, including children with no eczema. Furthermore, our results point to increased efficacy of the intervention with earlier age of introduction. https://doi.org/10.1111/all.15597