Insights into tree nut and sesame consumption from a cohort of 80 peanut‐allergic children.
Peanut allergy is increasing in prevalence in the US according to reports [1] and has become a global concern. Sensitization to tree nuts is common with reported rates of up to 86% for multi-nut sensitization with increasing age [2] [3]. In addition, peanut allergy has been associated with an increased risk of sesame sensitization and allergy [4]. Patients' attitudes towards tree nut and sesame consumption can be variable following a diagnosis of peanut allergy and have not previously been examined.
Chemically modified peanut extract shows increased safety while maintaining immunogenicity.
BACKGROUND: Peanuts are most responsible for food-induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity and immunotherapeutic efficacy of a well characterized chemically modified peanut extract (MPE) adsorbed to Al(OH)3. METHODS: Peanut extract (PE) was modified by reduction and alkylation. Using sera of peanut allergic patients, competitive IgE-binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE-specific T-cell lines and the induction of PE-specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH)3 was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut allergic mice. RESULTS: Compared to PE, the IgE-binding and capacity to induce allergic symptoms of MPE was lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH)3 . Both PE and MPE + Al(OH)3 showed to be efficacious in a model for immunotherapy. CONCLUSION: In our studies an Al(OH)3 adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained. The preclinical data presented in this study supports further development of modified peanut allergens for IT.
Identification of almond (Prunus dulcis) vicilin as a food allergen.
Almond is one of the tree nuts listed by US FDA as a food allergen source. A food allergen identified with patient sera has been debated to be the 2S albumin or the 7S vicilin. However, neither of these proteins has been defined as a food allergen. The purpose of this study was to clone, express, and purify almond vicilin and test whether it is a food allergen. Western blot experiment was performed with 18 individual sera from patients with double-blind, placebo-controlled clinical almond allergy. The results showed that 44% of the sera contained IgE antibodies that recognized the recombinant almond vicilin, indicating that it is an almond allergen. Identifying this and additional almond allergens will facilitate the understanding of the allergenicity of seed proteins in tree nuts and their cross-reactivity.
Different thermal processing effects on peanut allergenicity.
BACKGROUND: Peanut allergy is one of the most common food allergies worldwide. Studies have shown that the incidence of peanut allergies in Western-born Asians is higher than that in Asia-born Asians. Notably, Europeans and Americans mostly eat roasted peanuts, whereas Asians mostly eat boiled or fried peanuts. RESULTS: BALB/c mice were sensitized using purified protein from raw, roasted or boiled peanuts, then fed the same by oral gavage. The relevant allergic reactions were studied using BALB/c mice model, including a Rat Basophilic Leukemia (RBL) cell model, simulated gastric fluid experiments, and ultraviolet (UV) and Circular Dichroism (CD) spectrum analysis. The serological studies showed increased levels of IgE, IL-4, IL-5 and pathological studies showed mast cell degranulation,inflammatory changes in jejunal tissues with an increase in thymic stromal lymphopoietin (TSLP) gene expression in all treatment group compared with the control group (PBS). Compared with the raw peanut group, sera from the roasted peanut group produced a significant increase in RBL β-hexosaminidase A (β-HXA) release in vitro and roasted peanuts showed increased resistance to digestion in simulated gastric fluid experiments. Ultraviolet and CD spectrum analyses showed that the roasting and boiling processes altered the structure of the major peanut allergens, which may have contributed to the differences observed in peanut allergenicity. CONCLUSION: Our findings indicate that peanut allergies are related to peanut thermal processing methods. In our mouse model, the raw, roasted and boiled peanuts elicited different degrees of allergic response. Compared with raw peanut, roasted peanuts show a higher allergenicity, while the boiled peanuts show a lower allergenicity.
Heat and Pressure Treatments on Almond Protein Stability and Change in Immunoreactivity after Simulated Human Digestion.
Almond is consumed worldwide and renowned as a valuable healthy food. Despite this, it is also a potent source of allergenic proteins that can trigger several mild to life-threatening immunoreactions. Food processing proved to alter biochemical characteristics of proteins, thus affecting the respective allergenicity. In this paper, we investigated the effect of autoclaving, preceded or not by a hydration step, on the biochemical and immunological properties of almond proteins. Any variation in the stability and immunoreactivity of almond proteins extracted from the treated materials were evaluated by total protein quantification, Enzyme Linked Immunosorbent Assay (ELISA), and protein profiling by electrophoresis-based separation (SDS-PAGE). The sole autoclaving applied was found to weakly affect almond protein stability, despite what was observed when hydration preceded autoclaving, which resulted in a loss of approximately 70% of total protein content compared to untreated samples, and a remarkable reduction of the final immunoreactivity. The final SDS-PAGE protein pattern recorded for hydrated and autoclaved almonds disclosed significant changes. In addition, the same samples were further submitted to human-simulated gastro-intestinal (GI) digestion to evaluate potential changes induced by these processing methods on allergen digestibility. Digestion products were identified by High Pressure Liquid Chromatography-High Resolution Tandem Mass Spectrometry (HPLC-HRMS/MS) analysis followed by software-based data mining, and complementary information was provided by analyzing the proteolytic fragments lower than 6 kDa in size. The autoclave-based treatment was found not to alter the allergen digestibility, whereas an increased susceptibility to proteolytic action of digestive enzymes was observed in almonds subjected to autoclaving of prehydrated almond kernels. Finally, the residual immunoreactivity of the GI-resistant peptides was in-silico investigated by bioinformatic tools. Results obtained confirm that by adopting both approaches, no epitopes associated with known allergens survived, thus demonstrating the potential effectiveness of these treatments to reduce almond allergenicity.
Recent advances in understanding and preventing peanut and tree nut hypersensitivity.
Peanut allergy, the most persistent and deadly of the food allergies, has become more prevalent worldwide in recent decades. Numerous explanations have been offered for the rise in peanut allergy, which has been more pronounced in Western, industrialized nations. In infants who are at increased risk of peanut allergy, new evidence indicates that early introduction of peanuts can help prevent allergy development. This counterintuitive finding directly contradicts the previously established practice of peanut avoidance for high-risk infants but is supported by clinical and basic science evidence. Here, we review the literature contributing to our evolving understanding of nut allergy, emphasizing the translation of this work to clinical practice.
Managing Cross-Reactivity in Those with Peanut Allergy.
Peanut is an allergenic legume that can cross-react with other plant-based foods, notably other legumes and tree nuts. Peanut allergic individuals can be both co-sensitized as well as co-allergic to such items, requiring foresight when eliciting a clinical history of reaction, in the diagnostic evaluation of such allergies, and in the counseling of patients as to food avoidances after a diagnosis is made. Legume allergens belong to the Fabaceae family and encompass the cupin, prolamin, PR-10, and LTP families, which mediate cross-sensitization including that between peanut and tree nut. Among legumes, the most common patterns of clinical cross-reactivity are between peanut and lupine, peanut and soy, as well as chickpea and lentil, though this is highly dependent upon geography and prevalence of these foods in the diet. Issues of cross-sensitization may exist between peanut and certain tree nuts, as well as among tree nuts though such patterns do not always result in clinically relevant allergy. Molecular diagnostic testing may be a future tool to help parse out the aforementioned patterns, but oral food challenges are still the gold standard for accurate diagnosis. Though potential desensitization treatments have emerged for peanut allergy, these have not been developed for other legumes and most tree nuts, and desensitization to peanut has not proven to have an effect on legume cross-sensitization.
Prevalence, severity, and distribution of adult-onset food allergy.
Introduction: While much attention has been devoted to food allergy in children, little is known about the prevalence and characteristics of food allergy in adults. Moreover, recent research has shown that increasing numbers of individuals are developing food allergy in adulthood. This population-based study was conducted to examine the prevalence, severity, and distribution of adult-onset food allergy. Methods: A survey was administered to 40,443 adult United States residents between 2015 and 2016. Population-level prevalence was estimated using complex survey weighting. Demographics, history of reactions and diagnosis for each allergen, and comorbid conditions were analyzed. Self-reported food allergies were considered convincing if symptoms were consistent with IgE-mediated reactions. Results: Among all adults with food allergy, 45.3% reported developing at least one food allergy after 18 years of age. Of these, 24.9% only experienced onset of food allergy in adulthood, and 54.7% only experienced onset of food allergy in childhood. The five most prevalent adult-onset food allergies included shellfish (13.3% of adults), milk (6.0%), wheat (5.6%), tree nut (4.8%), and soy (3.9%). More than half of individuals with adult-onset allergy to peanut, tree nut, fin fish, or shellfish reported a prior severe reaction to the allergen. Factors associated with development of adult-onset food allergy include female sex, increasing age, and a history of multiple food allergies, allergic rhinitis, or medication allergy. Conclusions: One in four adults with food allergy develop a food allergy for the first time as an adult. Further study is necessary to understand potential predictors of adult-onset food allergy.
AR101 oral immunotherapy for peanut allergy.
BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776).
Severity of peanut allergy and the unmet gaps in care: a call to action.
Peanut allergy is one of the most common food allergies in children, with a prevalence that has been increasing over the past several decades. The allergy is a type I, immunoglobulin E (IgE)-mediated reaction that commonly presents in childhood and can be associated with an anaphylactic response. There are many theories that attempt to explain the increasing prevalence, including dietary changes, improvements in hygiene, and intentional allergen avoidance. Diagnosis is made through a combination of a thorough patient history, peanut-specific serum-specific IgE levels, peanut skin-prick test, and, if necessary, an oral food challenge. Guidelines based on the landmark 2015 Learning Early About Peanut Allergy trial suggest that peanuts should be introduced into the diet as early as 4 to 6 months of age in infants who are at highest risk of developing peanut allergy. It is important for providers to recognize risk factors for the development of peanut allergy, identify associated clinical symptoms, and provide an accurate diagnosis of patients to effectively manage them and their families and prevent future reactions.