Peanut Allergy Research Articles

Food Allergy in Children in China.

The prevalence of food allergies in China seems to be increasing, but there are limited studies describing the pattern of food allergies across the country. This review highlights regional variations observed across China, with data indicating a higher prevalence in the more economically developed eastern and southern coastal regions compared to inland areas. Egg and milk are the most common allergies among children under 3 years old; for children above 3 years old, specific food allergens also show regional differences, with shellfish allergies being more common in southern and eastern coastal areas, while wheat and fruit allergies are more prevalent in northern regions. Emerging peanut and tree nut allergies have also been observed in China's megacities, although the prevalence remains relatively low compared to Western countries. These geographic and environmental influences highlight the complexity of the food allergy landscape in China and the need for a more nuanced understanding of the underlying drivers. Despite the growing burden of food allergies, significant gaps exist in effectively managing these conditions in China. Lack of standardised diagnostic tools, limited access to oral food challenges and a shortage of trained allergists pose major challenges. Another critical gap is the limited availability and affordability of epinephrine autoinjectors, essential for managing life-threatening anaphylactic reactions. Addressing these systemic deficiencies in China's food allergy management infrastructure will require concerted efforts from policymakers, healthcare systems and pharmaceutical companies. Investing in the development of standardised diagnostics, expanding the allergy speciality workforce and ensuring equitable access to emergency care and treatment options are crucial steps towards improving health outcomes for the millions of individuals affected by food allergies in China.

Diagnostic Accuracy of Lipid Transfer Proteins (LTPs) Specific IgE Assay in Food Allergy: A Systematic Review

The aim of this systematic review was to evaluate the diagnostic accuracy of molecular-based LTPs serum sIgE for the diagnosis of food allergies in patients with suspected allergy to one of the LTPs-containing foods. Cohort, prospective or retrospective cross-sectional studies were considered for inclusion in this review. Oral food challenge (both open and double-blind placebo-controlled) was the reference standard for the diagnosis. PubMed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org were searched for relevant papers. The risk of bias was assigned by the QUADAS-2 tool. Data were reported as the sensitivity and specificity. The study protocol was registered in the PROSPERO database (CRD42022321985). Fifteen articles, including 2395 individuals, were included. The sensitivity of Ara h 9 for peanut allergy diagnosis ranged from 6 to 61%; the specificity ranged from 57 to 100%. The Cor a 8 sensitivity ranged from 11 to 43%, with the specificity ranging from 59 to 94%. Ara h 9 and Cor a 8 serum sIgE may be useful for confirming the diagnosis of peanut and hazelnut allergy in symptomatic patients, although the diagnostic accuracy is limited by the low sensitivity. More investigation on other LTPs and in adult populations may be important to define the clinical role of this test in food allergy diagnostics.

A Health Economic Analysis of Non-injectable Epinephrine Compared with Intramuscular Epinephrine

BackgroundNon-injectable epinephrine to treat allergic reactions addresses an unmet need. Intranasal epinephrine is approved and a sublingual form is under development. Inhaled epinephrine is poorly studied for anaphylaxis. These forms have unknown cost-effectiveness. ObjectiveThe aim of this research was to evaluate cost-effectiveness of commercially available non-injectable epinephrine compared with intramuscular epinephrine for treatment of anaphylaxis. MethodsMarkov cohort analyses evaluated the cost-effectiveness of non-injectable epinephrine forms. The base-case assumed exaggerated anaphylaxis fatality rates (50-fold increase) for using inhaled epinephrine given low certainty evidence in anaphylaxis, and deliberately reduced fatality risk for nasal or sublingual forms (10-fold reduction) theorizing higher adherence and early use during an allergic reaction. ResultsIn the base-case scenario, assuming a 10-fold decreased risk in peanut allergy fatality associated with intranasal or sublingual epinephrine treatment for a severe allergic reaction (net monetary benefit [NMB] $2,189,134) vs. intramuscular (IM) epinephrine use (NMB, 2,189,114), intranasal or sublingual epinephrine was the most cost-effective option (incremental cost-effectiveness ratio [ICER] $83,748/QALY), but only at a marginal annual cost of $4. IM epinephrine was cost-effective (ICER, $17,900/QALY) vs. inhaled epinephrine (NMB, $2,183,531), although inhaled epinephrine reached cost-effectiveness (Willingness To Pay [WTP $100,000/QALY]) if associated fatality risk fell below 2.5-fold. Substituting a single non-injectable form of epinephrine for a second injectable device (in patients prescribed two autoinjectors already) would be cost-effective; however, adding a supplemental non-injectable device was not cost-effective, even assuming a 10-fold risk reduction with multiple device carriage (ICER $858,462). ConclusionNon-injectable routes of epinephrine can be cost-effective options provided fatality risk is not significantly elevated. Carriage of redundant epinephrine autoinjectors with non-injectable forms is not cost-effective if associated with excess cost of redundant device packs.

Risk Subgroups and Intervention Effects Among Infants at High Risk for Peanut Allergy: A Model for Clinical Decision Making

Risk Subgroups and Intervention Effects Among Infants at High Risk for Peanut Allergy: A Model for Clinical Decision Making

Is gastrointestinal epithelial barrier dysfunction the only responsible for sensitization to food allergens?

Epithelial barriers are crucial defenses against pathogens and allergens, and recent theories suggest that environmental factors may compromise them, leading to type 2 inflammation and conditions such as asthma, atopic dermatitis, food allergy, and rhinitis. While skin and respiratory barriers show clear dysfunctions in allergies, the role of the gut epithelium is less defined, particularly in view of its ability to absorb nutrients and maintain immune tolerance under normal conditions. Research indicates that gastrointestinal barrier integrity typically remains preserved in food allergies, allowing for the development of immune tolerance to ingested food antigens through mechanisms like Treg cells and IgA. Allergies to cow's milk or hen's egg proteins most often resolve with age, highlighting the gut's evolving role in allergen sensitization. Studies like the LEAP (Learning Early About Peanut Allergy) trial demonstrate the preventive benefits of early allergen exposure against peanut allergy, supporting the dual allergen exposure hypothesis. New allergens such as alpha-Gal and gibberellin-regulated proteins (GRP) reveal distinct sensitization pathways beyond traditional ingestion routes, implicating non-dietary sources in allergen introduction. Altogether, there is lack of evidence suggesting that the intestinal epithelium is disrupted in food allergy.

Safety of oral immunotherapy for cashew nut and peanut allergy in children - a retrospective single-centre study.

Oral immunotherapy (OIT) is increasingly used for the treatment of childhood food allergies, with limited data available on cashew nut OIT. This real-life study investigated the safety and feasibility of cashew nut OIT, comparing it with peanut OIT, with a focus on the up-dosing process. We analysed cashew nut (n = 24) and peanut (n = 38) OIT cases with treatment initiated between 2018 and 2022 at the University Children's Hospital Basel. All patients who commenced therapy within this time frame were enrolled without prior selection. Two different starting protocols were used. Within the up-dosing protocol, the nut intake was incrementally increased by 20-30% every 2 weeks until reaching a maintenance dose of 1 g of nut protein. After consuming the maintenance dose regularly for 18-24 months, a second oral food challenge was performed. Patients who passed this challenge were considered desensitised. The safety of the therapy was evaluated based on the severity of adverse reactions during the up-dosing phase. Symptom severity was evaluated using the validated ordinal food allergy severity scale (o-FASS-5). Over the study period, 33% of cashew nut-allergic and 63% of peanut-allergic patients experienced mild to moderate allergic reactions. Severe allergic reactions occurred in five peanut-allergic children with high baseline allergen-specific IgE levels. Six patients with peanut, and none with cashew nut OIT, discontinued the therapy due to adverse reactions. The mean duration to reach the maintenance phase was longer for children with asthma or another food allergy. Among children who already underwent the second oral food challenge, desensitisation was achieved in 91% (11 out of 12) of cashew nut- and 73% (11 out of 15) of peanut-allergic patients. Cashew nut OIT had a low severity of adverse reactions and was generally well-tolerated. However, patient characteristics influenced side effect risk and treatment duration, emphasising the need for individualised OIT strategies.

The impact of coarsening an exposure on partial identifiability in instrumental variable settings.

In instrumental variable (IV) settings, such as imperfect randomized trials and observational studies with Mendelian randomization, one may encounter a continuous exposure, the causal effect of which is not of true interest. Instead, scientific interest may lie in a coarsened version of this exposure. Although there is a lengthy literature on the impact of coarsening of an exposure with several works focusing specifically on IV settings, all methods proposed in this literature require parametric assumptions. Instead, just as in the standard IV setting, one can consider partial identification via bounds making no parametric assumptions. This was first pointed out in Alexander Balke's PhD dissertation. We extend and clarify his work and derive novel bounds in several settings, including for a three-level IV, which will most likely be the case in Mendelian randomization. We demonstrate our findings in two real data examples, a randomized trial for peanut allergy in infants and a Mendelian randomization setting investigating the effect of homocysteine on cardiovascular disease.

Impact of Heat and Pressure Processing Treatments on the Digestibility of Peanut, Hazelnut, Pistachio and Cashew Allergens.

Food processing can alter protein biochemical properties, impacting immunoreactivity and allergenicity. A key feature of food allergens is their resistance to enzymatic digestion, particularly by pepsin and trypsin. This study compares the digestomes of raw and heat- and/or pressure-treated peanuts, hazelnuts, pistachios and cashews using the INFOGEST harmonized digestion protocol and analyzing their IgE-binding capacity through in vitro methods. Protein patterns from controls and digestomes were resolved by SDS-PAGE and tested with sera from allergic patients, confirmed by competitive ELISA for hazelnuts and peanuts. The results indicate that processing methods differently affect the gastrointestinal (GI) digestion of these allergens. Simulated GI digestion caused a significant destruction of protein structures, reducing but not eliminating IgE reactivity for all four nuts. Boiling for 60 min did not change the SDS-PAGE profiles, but it did stimulate enzymatic activity, decreasing IgE binding capacity. In contrast, applying heat and pressure led to a nearly complete inhibition of allergenic potential during simulated digestion. These findings suggest that employing intense food processing techniques and investigating the gastrointestinal effects of highly allergenic nuts could be crucial steps toward developing new hypoallergenic formulations.

Comparing Two Peanut Desensitization Protocols in Preschool Children: A Real-World Clinical Practice.

Peanut allergy is the main food allergy in childhood and poses significant health concerns. This study aimed to critically evaluate the effectiveness and safety of oral immune therapy (OIT) using crushed peanuts versus peanut puffs. Children with an allergist diagnosed peanut allergy based on a history of an IgE-mediated reaction and a positive skin prick test for peanuts were recruited at the Montreal Children's Hospital and the Children's Clinic located in Montreal. Based on age and personal preference, initial doses of peanut were given in either puff (Bamba) or crushed peanut form. Patients continued the same dose for 2-5 weeks at home, filled out a symptom diary, and returned to the clinic for up-dosing until maintenance was reached (2 teaspoons of peanut butter). A continuation ratio regression model was used to evaluate the effect of the allergen type on the severity of anaphylactic and allergic reactions (ARs) during OIT while adjusting for potential confounders. Between October 2020 and June 2023, 191 children (59.6% male; median age 1.95 years) were recruited. Most patients (75.1%) had eczema, and 12.7% had asthma. Oral desensitization was performed using one of two strategies according to the allergist: crushed peanut (n = 60 [31.4%]) and peanut puff (n = 131 [68.6%]). Of the participants, the consumption of puff lowered reaction severity by a factor of 3.94 (95% CI, 1.6-9.6), in comparison to crushed peanuts. Older age markedly elevates the adjusted odds of reacting to a particular severity level as compared to a lower level by 1.20 (95% CI, 1-1.4). Modified peanut desensitization using peanut puffs has shown potential in reducing the severity of ARs in younger children. Older children may experience a higher risk of severe reactions, indicating the need for age-specific approaches to desensitization protocols.

Fungal Proteases in the Preventative Treatment of Peanut Allergies: A Research Protocol

Fungal Proteases in the Preventative Treatment of Peanut Allergies: A Research Protocol

EAACI guidelines on the management of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes.

Development of Cashew and Pistachio Ladders through a Food-Processing Approach.

Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modification, specifically soaking and boiling (1-4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an "allergen ladder". An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy.

LUPIN FOOD ALLERGY AND CROSS REACTIVITY WITH PEANUT ALLERGY

LUPIN FOOD ALLERGY AND CROSS REACTIVITY WITH PEANUT ALLERGY

Safety and adherence of early oral immunotherapy for peanut allergy in a primary care setting: a retrospective cross-sectional study

BackgroundPeanut allergy is a common food allergy with potentially life-threatening implications. Early oral immunotherapy for peanut allergy (P-EOIT) has been shown to be effective and safe in research and specialty clinic settings. Provision of P-EOIT in primary care would make it available to more patients. We sought to assess the safety of P-EOIT in a primary care setting by documenting the rates of peanut-related allergic reactions leading to emergency department (ED) visits and use of epinephrine. We also examined adherence by assessing the percentage of patients reaching maintenance phase and continuing ingestion after one year of P-EOIT.MethodsThis retrospective study included all patients aged less than 36 months who started P-EOIT at a primary care allergy clinic in New Brunswick, Canada, from 2016 to 2020. The population included patients who (1) had a history of an allergic reaction to peanuts with a positive skin prick test or positive peanut specific IgE level (ps-IgE) or (2) no history of ingestion and a baseline ps-IgE ≥5 kU/L. Patients had biweekly clinic visits with graded increases in peanut protein up to a maintenance dose of 300 mg of peanut protein daily. A blinded retrospective review of paper charts and electronic medical records was conducted along with phone interviews regarding ED visits and epinephrine use.ResultsAll 69 consented patients reached maintenance dose over a median of 29 weeks, and 66 patients (95.7%) were still regularly consuming peanut protein after 1 year of maintenance. One patient had a peanut ingestion-related ED visit requiring epinephrine during the escalation phase of peanut protein dosing (1.4%). During the first year of maintenance phase, no patients had peanut ingestion-related ED visits nor required epinephrine.ConclusionEarly oral immunotherapy for peanut allergy in a primary care setting appears to be safe and our findings suggest that it does not lead to an increased burden of emergency department visits. Our population had high adherence rates, with the majority achieving maintenance dose and staying on this dose for one year.

The effects of ultrasound-assisted glycation on the allergenicity and functional properties of peanut proteins

This study investigated the effects of ultrasound-assisted glycation on the allergenicity and functional properties of peanut proteins. Results showed that ultrasound-assisted glycation increased the degree of glycation reaction of peanut proteins significantly (P < 0.05). ELISA results indicated that the binding of peanut allergens with serum immunoglobulin G (IgG) and immunoglobulin E (IgE) was significantly decreased (P < 0.05). Furthermore, secondary structure analysis revealed a significant increase in β-sheet content, alongside decreases in α-helix, β-turn, and random coil contents (P < 0.05). In addition, intrinsic fluorescence intensity, surface hydrophobicity, and ultraviolet (UV) spectra intensity were diminished (P < 0.05), indicating notable changes in both secondary and tertiary structures of peanut proteins. Moreover, emulsification property, antioxidant activity and in vitro digestibility of peanut proteins showed the most obvious improvements following ultrasound-assisted glycation, and the solubility was increased while turbidity was decreased significantly (P < 0.05). In conclusion, this study demonstrated that ultrasound-assisted glycation not only effectively reduced the allergenicity of peanut allergens, but also improved the overall functional properties of peanut proteins, and the changes in sensitization and functional properties might be closely related to structural changes. This study will provide a theoretical basis for the development of peanut products.

Breakthrough in allergy mitigation using an innovative steam pressure-based processing technique

Peanuts are recognized as one of the most common allergenic foods, known to induce severe Th2-mediated allergic reactions. The resulting global health concern has fostered the necessity to design innovative technologies capable of mitigating allergenicity. This study investigated the effect of an innovative thermomechanical process, “Intensification of Vaporization by Decompression to the Vacuum” (IVDV), on the protein content and immunogenicity of whole peanuts. Through animal studies using peanut allergy BALB/c mouse models, this research revealed a clear reduction in allergic symptoms once challenged with IVDV-treated peanut protein extract, compared to those receiving raw or deep-fried peanut protein extracts. Significant changes in immune response markers in animals were observed, including reduced levels of histamine, Th1/Th2 cytokines, and antibodies, thus confirming the efficacy of IVDV in mitigating allergenicity in peanuts. Saturated steam pressure was demonstrated to have a highly significant positive effect on the reduction of protein content in IVDV-treated samples through degradation, with a noteworthy reduction ranging from 42.3% to 89.2%. This pilot study embarked on a pioneering exploration into the ability of IVDV to offer a viable solution in reducing peanut allergenicity, opening new avenues for enhanced food safety and inclusivity. The ease of scalability of IVDV technology to an industrial level, along with its cost-efficiency, further enhance its appeal for widespread adoption.

Whole Blood Transcriptomics Identifies Differences in Innate Immune Pathway Expression in Infants at Risk for Peanut Allergy.

Whole Blood Transcriptomics Identifies Differences in Innate Immune Pathway Expression in Infants at Risk for Peanut Allergy.

Recycled lithium battery nanomaterials as a sustainable nanofertilizer: Reduced peanut allergenicity and improved seed quality

The rapidly increasing amount of end-of-life lithium iron phosphate (LiFePO4) batteries has raised significant environmental concerns. This study offers a strategy for a paradigm shift by transforming this growing waste into a valuable resource by recycling discarded LiFePO4 batteries and safely integrating the materials into sustainable agriculture. We used five types of LiFePO4 (10, 50 mg kg−1) applied to soil planted with peanuts in a full-culture experiment. Our results show that addition of <50 mg kg−1 of recycled nano-LiFePO4 (rn-LiFePO4) has a multifaceted positive impact on peanut because of sustainable release of nutrients and nano-specific effects, not only enhancing photosynthesis and root growth but also increasing yield by 22 %–34 % while simultaneously elevating seed nutritional quality. Moreover, a remarkable reduction (up to 99.78 % at 10 mg kg−1 rn-LiFePO4) in the expression of allergen genes was evident following exposure to LiFePO4, which showed a significant negative correlation with Fe content in the seeds. The decreased peanut allergen gene expression was mediated by a downregulation of metabolites associated with protein digestion and absorption. Furthermore, rhizosphere soil immune system enhancement may indirectly enhance immune responses to peanut allergy. This study suggests the significant potential of nanoscale LiFePO4 recycled from Li battery, including enhancing crop yield quality and mitigating peanut allergy concerns while simultaneously addressing a growing waste stream of concern.

Diagnostic Accuracy of Skin Prick Test, Food-Specific IgE and Component Testing for IgE-Mediated Peanut, Egg, Milk and Wheat Allergy.

Diagnostic Accuracy of Skin Prick Test, Food-Specific IgE and Component Testing for IgE-Mediated Peanut, Egg, Milk and Wheat Allergy.

Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management

BackgroundFood allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective. PurposeThis study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments. MethodsTo elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome. ResultsGpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice. ConclusionTo conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.