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Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher rates in the RNA of highly allergenic legumes. Transcripts from peanut, soybean, sesame, and mite allergens contained a higher density of gaps than those of nonallergens. Allergen transcripts translate into proteins with a cationic carboxy terminus depleted in hydrophobic residues. In mice, recombinant TI variants of the peanut allergen Ara h 2, but not the canonical allergen itself, induced, without adjuvant, the production of anaphylactogenic specific IgE (sIgE), binding to linear epitopes on both canonical and TI segments of the TI variants. The removal of cationic proteins from bovine lactoserum markedly reduced its capacity to induce sIgE. In peanut-allergic children, the sIgE reactivity was directed toward both canonical and TI segments of Ara h 2 variants. We discovered 2 peanut allergens, which we believe to be previously unreported, because of their RNA-DNA divergence gap patterns and TI peptide amino acid composition. Finally, we showed that the sIgE of children with IgE-negative milk allergy targeted cationic proteins in lactoserum. We propose that it is not the canonical allergens, but their TI variants, that initiate sIgE isotype switching, while both canonical and TI variants elicit clinical allergic reactions.

Background/purpose: To evaluate the relationship between serum-specific immunoglobulin E (IgE) to peanuts/tree nuts and their clinical manifestations in atopic diseases., Method: Serum from people with the classical symptoms of asthma, allergic rhinitis (AR), or atopic dermatitis (AD) was collected for the measurement of serum-specific IgE to peanuts, cashew nuts, Brazil nuts, almonds, and coconuts. Cases with possible sensitization to these nuts (serum specific IgE ≧ 0.35 kU/L) were selected and their clinical relationships with physician-diagnosed asthma, allergic rhinitis, or atopic dermatitis were analyzed., Result: Compared with non-sensitization group, people with peanut/tree nut sensitization have higher prevalence of atopic dermatitis, but no such difference noted in the prevalence of allergic rhinitis. In the situation of asthma, people with sensitization to peanuts and Brazil nuts, but not other nuts, have higher prevalence of asthma than people without sensitization to any nut (p < 0.001 and p < 0.05, respectively). Binary logistic regression analysis also showed positive associations between peanut (OR: 1.164, p value = 0.017) and Brazil nut (OR: 1.304, p value = 0.055) sensitization and asthma. The associations between peanut and Brazil nut sensitization and asthma were independent of the prevalence of other atopic diseases., Conclusion: People in Asia may have less severe allergic effects as in Western countries, but sensitization to specific food allergens such as peanuts or Brazil nuts may predispose individuals to asthma, which could be helpful in diagnosis and deserves more attention than previously considered., (Copyright © 2019. Published by Elsevier B.V.)

Background: Bioaccessibility of food allergens may be a key determinant of allergic reactions., Objective: To develop a protocol allowing the detection of the major peanut allergen, Ara h 6, in the bloodstream following ingestion of low amounts of peanut and to compare Ara h 6 bioaccessibility by food matrix. We further assessed for differences in absorption in healthy versus peanut-allergic volunteers., Methods: A blood pretreatment combining acidic shock and thermal treatment was developed. This protocol was then applied to blood samples collected from human volunteers (n = 6, healthy controls; n = 14, peanut-allergic patients) at various time-points following ingestion of increasing levels of peanut incurred in different food matrices (cookies, peanut butter and chocolate dessert). Immunodetection was performed using an in-house immunoassay., Results: An original pretreatment protocol was optimized, resulting in irreversible dissociation of human antibodies-Ara h 6 immune complex, thus rendering Ara h 6 accessible for its immunodetection. Ara h 6 was detected in samples from all volunteers following ingestion of 300-1000 mg peanut protein, although variations in the kinetics of passage were observed between individuals and matrices. Interestingly, in peanut-allergic subjects, Ara h 6 could be detected following ingestion of lower doses and at higher concentrations than in non-allergic volunteers., Conclusions and Clinical Relevance: The kinetics and intensity of Ara h 6 passage in bloodstream depend on both individual and food matrix. Peanut-allergic patients appear to demonstrate higher absorption rate, the clinical significance of which warrants further evaluation., (© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Epicutaneous immunotherapy (EPIT) for peanut allergy is a potential novel immunotherapy that utilizes the unique cutaneous immunologic properties to induce desensitization. A randomized, double-blind, placebo-controlled Phase 3 trial (PEPITES) in peanut-allergic children 4-11 years demonstrated an epicutaneous patch (DBV712) with 250 µg peanut protein was statistically superior to placebo in inducing desensitization following 12 months of daily treatment. Objective: To investigate what baseline and in-study factors influenced response to DBV712 250 µg, with a focus on patch adhesion, by posthoc analysis of PEPITES data. Methods: A posthoc multivariate model built with log-transformed Month 12 eliciting dose (ED) as the dependent variable was used to assess the influence of baseline characteristics and patch adhesion. Baseline characteristics and treatment response were also evaluated by stratifying subjects into decile subgroups by patch detachment rates over the 12-month study. Results: Multivariate analysis identified higher baseline ED and lower baseline peanut-specific IgE as the variables most predictive of higher Month 12 ED, followed by mean daily patch application duration, baseline SCORing Atopic Dermatitis (SCORAD) score, and age. By decile stratification, no association between patch detachment and treatment response was identified for 80% of DBV712-treated subjects. All DBV712-treated subjects, including those with the highest patch detachment rates, demonstrated treatment benefit measured by fold-changes in geometric mean ED. Conclusion: We identified subject baseline characteristics of higher baseline ED and lower baseline peanut-specific IgE as most predictive of higher Month 12 ED. For the majority of treated subjects, patch detachment did not impact treatment response. A minority of subjects, highly sensitive to peanut at baseline, had lower prespecified responder rates and higher patch detachment rates, yet still benefited from treatment based upon fold-changes in ED.

Background: Oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity., Objective: Our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut., Methods: We assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2-specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC., Results: When a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2-specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients., Conclusions: The BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Peanut oral immunotherapy (POIT) is a novel and active form of treatment for patients with peanut allergy, with multiple research studies supporting its efficacy and safety. However, there are limited data available on changes in patients' quality of life (QoL) after successful desensitization. The Food and Drug Administration in the United States recently approved the first POIT drug for commercial use., Objective: To evaluate the QoL of patients with peanut allergy receiving POIT in a real-world academic setting., Methods: Twenty-one patients aged 4 to 17 years with a physician-established diagnosis of peanut allergy were offered POIT. Quality-of-life scores were assessed with the use of a validated Food Allergy Quality of Life questionnaire. Changes in quality-of-life scores were measured for each patient before and after POIT. The Wilcoxon signed-rank test was used to compare the distributions of scores before and after therapy., Results: We noted a statistically significant drop (reflecting improvement in the QoL) in the overall Food Allergy Quality of Life score (median 3.70 vs 2.97, P = .049) between baseline and successful desensitization to 300-mg peanut protein. In addition, the Social and Dietary Limitations subscale score (median 4.33 vs 2.89, P = .02) and the Food Allergy Independent Measure score (median 3.17 vs 2.22, P = .001) also improved significantly after therapy., Conclusion: We report a significant improvement in the overall QoL before and after POIT treatment, with fewer concerns about accidental exposures and severity of allergic reactions as well as fewer limitations in dietary choices and social interactions., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Peanut allergic individuals can be both co-sensitized and co-allergic to peanut and tree nuts. At the moment, standard diagnostic approaches do not always allow differentiation between clinically relevant sensitization and nonsignificant cross-reactions, and the responsibility of each allergen remains unclear. The objective of this study was therefore to determine a peanut sensitization profile in a cohort of Canadian peanut allergic children and assess the immunoglobulin E (IgE) molecular cross-reactivity between peanut, almond, hazelnut and pistachio. The specific IgE (sIgE) levels of each patient serum were determined by ImmunoCAP, indirect ELISA and immunoblot to examine their sIgE-binding levels and profiles to peanut proteins. Reciprocal inhibition ELISA and immunoblotting were used to study sIgE cross-reactions between peanut and the selected tree nuts using an adjusted and representative serum pool of the nine allergic patients. The results showed that the prepared peanut and tree nut protein extracts allowed for the detection of the majority of peanut and selected tree nut known allergens. The reciprocal inhibition ELISA experiments showed limited sIgE cross-reactivities between peanut and the studied tree nuts, with peanut being most likely the sensitizing allergen and tree nuts the cross-reactive ones. In the case of hazelnut and pistachio, a coexisting primary sensitization to hazelnut and pistachio was also demonstrated in the serum pool. Reciprocal inhibition immunoblotting further revealed that storage proteins (2S albumin, 7S vicilin and 11S legumin) could possibly account for the observed IgE-cross-reactions between peanut and the studied tree nuts in this cohort of allergic individuals. It also demonstrated the importance of conformational epitopes in the exhibited cross-reactions.

Scope: Factors such as food processing, the food matrix, and antacid medication may affect the bio-accessibility of proteins in the gastrointestinal tract and hence their allergenic activity. However, at present they are poorly understood., Methods and Results: Roasted peanut flour was incorporated into either a chocolate dessert or cookie matrix and bio-accessibility were assessed using an in vitro digestion system comprising a model chew and simulated gastric and duodenal digestion. Protein digestion was monitored by SDS-PAGE and immunoreactivity analyzed by immunoblotting and immunoassay. IgE reactivity was assessed by immunoassay using serum panels from peanut-allergic subjects. Roasted peanut flour proteins proved highly digestible following gastro-duodenal digestion even when incurred into a food matrix, with only low molecular weight polypeptides of Mr < 8 kDa remaining. When gastric digestion was performed at pH 6.5 (simulating the effect of antacid medication), peanut proteins are not digested; subsequent duodenal digestion is also limited. IgE reactivity of the major peanut allergens Ara h 1, Ara h 2, and Ara h 6, although reduced, was retained after oral-gastro-duodenal digestion irrespective of digestion conditions employed., Conclusion: Peanut allergen bio-accessibility is unaffected by the dessert or cookie matrices whilst high intra-gastric pH conditions render allergens more resistant to digestion., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Peanut allergy is a growing public concern; however, little is known about the immunological mechanism(s) that initiate the disease process. Our knowledge is also limited regarding the role of group 2 innate lymphoid cells (ILC2s) in regulating humoral immunity. To fill these major gaps in our knowledge, we investigated the immunological mechanisms involved in peanut allergen sensitization by using mouse models. To mimic environmental exposure in humans, naive BALB/c mice were exposed to peanut flour by inhalation without any exogenous adjuvants. When exposed to peanut flour, naive mice developed T follicular helper (Tfh) cells in their lung draining lymph nodes and produced IgE Abs to peanuts. Mice deficient in IL-13 showed decreased numbers of Tfh cells and germinal center B cells and produced significantly fewer IgE Abs. IL-13 was necessary and sufficient for induction of CD11c + MHC class II hi dendritic cells that are implicated in Tfh cell development. Importantly, lung ILC2s served as a predominant early source of IL-13 when naive mice were exposed to peanut flour. Furthermore, mice that are deficient in lung ILC2s by bone marrow transfer from Rora sg/sg mice or by genetic manipulation produced significantly fewer IgE Abs to peanuts compared with control mice. These findings suggest lung ILC2s that serve as a rapid source of IL-13 upon allergen exposure play a major role in Tfh cell development, IgE Ab production, and initiation of peanut allergy., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Background: Web blotch is one of the most important foliar diseases worldwide in peanut (Arachis hypogaea L.). The identification of quantitative trait loci (QTLs) for peanut web blotch resistance represents the basis for gene mining and the application of molecular breeding technologies., Results: In this study, a peanut recombinant inbred line (RIL) population was used to map QTLs for web blotch resistance based on high-throughput genome-wide sequencing. Frequency distributions of disease grade and disease index in five environments indicated wide phenotypic variations in response to web blotch among RILs. A high-density genetic map was constructed, containing 3634 bin markers distributed on 20 peanut linkage groups (LGs) with an average genetic distance of 0.5 cM. In total, eight QTLs were detected for peanut web blotch resistance in at least two environments, explaining from 2.8 to 15.1% of phenotypic variance. Two major QTLs qWBRA04 and qWBRA14 were detected in all five environments and were linked to 40 candidate genes encoding nucleotide-binding site leucine-rich repeat (NBS-LRR) or other proteins related to disease resistances., Conclusions: The results of this study provide a basis for breeding peanut cultivars with web blotch resistance.

Introduction: Previous studies in humans support the dual-allergen exposure hypothesis, and several studies in mouse models have demonstrated that cutaneous exposure to disrupted or intact skin can lead to sensitization to peanut. However, the field lacks definitive evidence that cutaneous exposure leads to peanut allergy in humans or other primates., Methods: Peanut extract was applied to the shaved back of the neck of four male and four female African green monkeys three times per week for 4 weeks. An oral food challenge (OFC) was performed the following week by gavage of 200 mg of peanut protein, and vital signs were monitored for 30 minutes post-OFC. Blood was collected at baseline, day 11, day 32, and 30 minutes post-OFC. Total IgE, and peanut-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) were quantified in serum collected throughout the 4 weeks. Histamine was measured in serum collected 30 minutes post-OFC., Results: Peanut-specific IgE was undetectable at any time points in any of the monkeys, and there was no consistent increase in total IgE. During the oral challenge, none of the monkeys experienced allergic symptoms and histamine levels did not change. However, seven of the eight monkeys produced increasing peanut-specific IgG by day 32, indicating that repeated skin exposure to peanut is immunogenic., Conclusions: Skin exposure to peanut did not lead to sensitization in this study, and monkeys did not experience anaphylaxis upon peanut challenge. However, monkeys produced increased peanut-specific IgG throughout peanut exposure, indicating that repeated skin exposure to peanut is immunogenic., (© 2020 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction and Objectives: Eosinophilic esophagitis (EoE) is frequently miss-diagnosed or overlooked for several years because of the invasiveness of investigations and the non-specificity of symptoms in childhood. Due to the lack of specific recommendations in children, its management remains very heterogeneous, especially concerning allergy testing. The aim of this study is to analyze our population and practices, in comparison with the literature, with a focus on allergic management, to harmonize and optimize our practice., Material and Methods: We included all children with a diagnosis of EoE at the Hospital Femme Mere Enfant, Bron, France. Data were collected via retrospective chart review., Results: 108 patients were included with an average age of 9.5 years. Average delay before diagnosis was 6.65 years. Symptoms varied with age, with a predominance of vomiting (60% of patients), feeding difficulties (72%) and growth difficulties (24%) in children <5 years, whereas older children often presented with feeding blockage (64%) and dysphagia (61%). Cough was frequent in our cohort (18.5%), especially in children <10 years (38.5% between three and five years). The allergic background was frequent (70.3%) and 80% of our patients benefited from allergy testing. Allergy testing was particularly useful to guide therapy as elimination diet represented an effective treatment in 60% of our patients CONCLUSIONS: Allergy testing has to be harmonized to include major allergens (egg, milk, peanut, fish, wheat, and soy), including prick and patch tests. Allergy-testing based diet seemed to be the best compromise between efficiency and constraints, especially in mono-sensitized patients., (Copyright © 2019 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were published for 11 allergenic foods in 2014. Systematic data collection has continued (2011-2018) and the dataset now contains over 3400 data points. The current study provides new and updated EDp values for 14 allergenic foods and incorporates a newly developed Stacked Model Averaging statistical method for interval-censored data. ED01 and ED05 values, the doses at which 1%, and respectively 5%, of the respective allergic population would be predicted to experience any objective allergic reaction were determined. The 14 allergenic foods were cashew, celery, egg, fish, hazelnut, lupine, milk, mustard, peanut, sesame, shrimp (for crustacean shellfish), soy, walnut, and wheat. Updated ED01 estimates ranged between 0.03 mg for walnut protein and 26.2 mg for shrimp protein. ED05 estimates ranged between 0.4 mg for mustard protein and 280 mg for shrimp protein. The ED01 and ED05 values presented here are valuable in the risk assessment and subsequent risk management of allergenic foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Peanut allergy is one of the most common food allergies in children, with increasing prevalence over time. The dual-allergen exposure hypothesis now supports transcutaneous sensitization to peanut as a likely pathophysiologic mechanism for peanut allergy development. As a result, there is emerging evidence that early peanut introduction has a role in peanut allergy prevention. Current first-line diagnostic tests for peanut allergy have limited specificity, which may be enhanced with emerging tools such as component-resolved diagnostics. Although management of peanut allergy includes avoidance and carrying an epinephrine autoinjector, risk of fatal anaphylaxis is extremely low, and there is minimal risk related to cutaneous or inhalational exposure. Quality of life in children with peanut allergy requires significant focus. Moving forward, oral and epicutaneous immunotherapy are emerging and exciting tools that may have a role to play in desensitization to peanut., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Abrams is a member of the scientific advisory board for Food Allergy Canada. Dr Chan has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, and Kaleo; is a member of the scientific advisory board for Food Allergy Canada; and was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases–sponsored guidelines for peanut allergy prevention. Dr Sicherer reports royalty payments from UpToDate and from Johns Hopkins University Press; grants to his institution from the National Institute of Allergy and Infectious Diseases, from Food Allergy Research and Education, and from HAL Allergy; and personal fees from the American Academy of Allergy, Asthma, and Immunology outside of the submitted work. He was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases–sponsored guidelines for peanut allergy prevention., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: Peanut allergy has historically been difficult to manage, with most cases persisting into adulthood. Novel therapies for peanut allergy treatment are on the horizon, yet allergists must maintain a robust understanding of the risks and benefits of the current standard of therapy, avoidance diet., Data Sources: A comprehensive literature search using PubMed of reviews and clinical articles was performed., Study Selections: Articles discussing peanut or other food-related allergic reactions, accidental exposures or anaphylaxis pertinent to avoidance diet or comparative to oral immunotherapy trials were selected., Results: Peanut remains a leading allergen associated with accidental ingestions responsible for food-related reactions, both mild and severe. Fatal reactions, however, are rare and measures such as anaphylaxis plans can significantly decrease the risk of accidental anaphylaxis. Patients may over estimate situations thought to increase risk for reactions to peanut, such as inhalation or contact through skin. In oral immunotherapy trials, the rate of anaphylaxis secondary to treatment was significantly higher than avoidance practices., Conclusion: Clinicians should continue to discuss avoidance as a viable option for long-term peanut allergy management and empower patients to differentiate relevant situations in which accidental reactions might occur., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Peanut allergy (PNA) is an IgE-mediated immune disorder, which merits particular attention due to its impact on the health and quality of life of millions of patients worldwide. PNA tends to develop in early life and resolves in only 20% of peanut-allergic children. It accounts for the majority of severe food-related allergic reactions. An accurate diagnosis of PNA is vital. In this review, we present the approach to the diagnosis of peanut allergy, starting from the history and proceeding to measures of overall sensitization and then to component-resolved diagnostics and oral food challenges as indicated. Additional testing in development includes basophil activation testing and determination of epitopes for peanut-allergic responses. Based on the literature, stepwise approaches and predictive models for diagnosing PNA are also presented., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Cross-reactive carbohydrate determinant (CCD) structures found in plant and insect glycoproteins are commonly recognized by IgE antibodies as epitopes that can lead to extensive cross-reactivity and obscure in vitro diagnostic (IVD) serology results. With the introduction of component resolved diagnosis (CRD), recombinant non-glycosylated components have been utilized to mitigate the risk of CCD-specific IgE (sIgE) detection. However, a recent study has shown that CCD-sIgE may bind directly to the cellulose solid phase matrix used in certain in vitro diagnostic assays, eliminating the advantage of CRD over traditional extract-based testing. The aim of this study is to further investigate the prevalence of CCD-sIgE interference on a commonly-used in vitro sIgE automated platform which employs a cellulose-based matrix to immobilize CCD-free recombinant components., Methods: Sera from patients sensitized to peanut, silver birch, and/or timothy grass were analyzed for CCD-sIgE reactivity on ImmunoCAP/Phadia and NOVEOS autoanalyzers against the MUXF3 carbohydrate component. Positive CCD-sIgE sera were further analyzed against non-glycosylated recombinant components bound to the ImmunoCAP solid phase in the absence and presence of a soluble CCD inhibitor. For comparison, sera were then analyzed on NOVEOS, a non-cellulose based automated sIgE assay., Results: Sera from 35% of the sensitized population tested in this study were positive (≥0.35 kU/L) for CCD-sIgE. Of those positives, 17% resulted in CCD-sIgE-positive (false positive) results on ImmunoCAP using non-glycosylated allergosorbents that were negative on NOVEOS. Sera producing false-positive results on ImmunoCAP had varying levels of CCD-sIgE from 0.67 kU/L to 36.52 kU/L. The incidence of CCD interference was predominantly delimited to low-positive IgE results (0.35 kUA/L- 3.00 kUA/L)., Conclusion: Falsely elevated diagnostic allergen-sIgE results can commonly occur due to the presence of CCD-sIgE using assays that employ a carbohydrate matrix-based allergosorbent. Even the use of non-glycosylated recombinant allergenic components coupled to cellulose matrices do not reduce their risk of detection. The risk of CCD interference that compromises quantitative IgE results can be mitigated by the addition of a soluble CCD inhibitor to positive CCD-sIgE containing sera or by alternatively using a non-cellulose based sIgE assay, such as the NOVEOS assay., Competing Interests: The authors of this manuscript have the following competing interests: Authors [ES, CO, CL, SN, LD, KR, EW] are employees of HYCOR Biomedical LLC. The funder (HYCOR Biomedical LLC) provides support in the form of salaries for authors [ES, CO, CL, SN, LD, KR, EW], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the author’s adherence to PLOS ONE policies in sharing data and materials.

Background: We previously reported attenuation of serum OVA-specific IgE levels and of lymphocyte-derived IL-4, both nominal markers of allergic immunity, following injection of a combination of homologous (mouse) polyclonal anti-idiotypic immunoglobulin (Ig) and immune Ig in BALB/c mice. We predicted this might generalize to other species and using heterologous mixtures of Igs. This was assessed in mice using OVA sensitization in the presence of human Igs as a source of both anti-idiotype Ig and immune Ig and in dogs with peanut butter-induced allergic responses., Methods: Eight-week-old BALB/c mice received OVA immunization and 5 weekly injections of immune Ig or anti-idiotype Ig from either homologous (mouse) or heterologous (human) sources. Five-month-old Beagles received weekly topical exposure (on the abdomen) to peanut butter and treatment with pooled dog Ig and dog antirabies immune Ig, or a combination of human IMIG and human anti-Tet. All mice/dogs thereafter received a final allergen challenge, and serum IgG, IgE, and allergen-induced IL-2/IL-4 and IL-31 production in 72 hr cultures was measured., Results: In mice attenuation of OVA-induced allergy (IgE-specific Ig and OVA-induced IL-4) was seen using both mouse and human Ig mixtures, without effect on OVA serum IgG or OVA-induced IL-2. Attenuation of concanavalin A- (ConA-) induced IL-4 : IL-2 production and of peanut butter-induced IL-4 and IL-31 was seen in dogs receiving combinations of both heterologous and homologous immune Igs and anti-idiotype Igs, with no decline in IL-2 production. Allergen-specific IgE/IgG was not detectable in dog serum, but there was a trend to lower total serum IgE levels (and decreased IgE : IgG ratios)., Conclusion: Homologous and heterologous combinations of polyclonal IMIG and immune Ig attenuate allergic responses in mice and dogs. This treatment protocol represents a novel approach which can be adapted for allergic desensitization in veterinary and human use., Competing Interests: G Hoffmann and RM Gorczynski declare purchase of shares in NI Inc. G Hoffmann is a member of the Research Advisory Board of NI Inc. T Maqbool has no competing interests. None of the authors is a paid employee of NI Inc., and no one received any remuneration for work performed in this study., (Copyright © 2020 R. M. Gorczynski et al.)

Purpose of the Review: Peanut oral immunotherapy (OIT) is one of the most studied experimental therapies for food allergy. With the recently FDA-approved peanut product, Palforzia, the goal of this article is to review the most recent data from clinical trials, discuss recent trends, and anticipate future developments., Recent Findings: The latest research suggests that peanut OIT could be a promising option for peanut-allergic patients, with the majority of participants in research studies achieving the primary efficacy endpoint of desensitization, as well as sustained unresponsiveness in select populations. Some studies also showed improvements in food allergy-related quality of life. However, peanut OIT is not without risk or side effects, including potentially serious allergic reactions. Future research will need to evaluate the short- and long-term effectiveness of the therapy in the real-world setting, predictors of important treatment outcomes, and the use of adjunctive therapies that may mitigate some of these allergic reactions.

Background: Unexpected allergic reactions to peanut are the most common cause of fatal food-related anaphylaxis. Mechanisms underlying the variable severity of peanut-allergic reactions remain unclear., Objectives: We sought to expand mechanistic understanding of reaction severity in peanut allergy., Methods: We performed an integrated transcriptomic and epigenomic study of peanut-allergic children as they reacted in vivo during double-blind, placebo-controlled peanut challenges. We integrated whole-blood transcriptome and CD4 + T-cell epigenome profiles to identify molecular signatures of reaction severity (ie, how severely a peanut-allergic child reacts when exposed to peanut). A threshold-weighted reaction severity score was calculated for each subject based on symptoms experienced during peanut challenge and the eliciting dose. Through linear mixed effects modeling, network construction, and causal mediation analysis, we identified genes, CpGs, and their interactions that mediate reaction severity. Findings were replicated in an independent cohort., Results: We identified 318 genes with changes in expression during the course of reaction associated with reaction severity, and 203 CpG sites with differential DNA methylation associated with reaction severity. After replicating these findings in an independent cohort, we constructed interaction networks with the identified peanut severity genes and CpGs. These analyses and leukocyte deconvolution highlighted neutrophil-mediated immunity. We identified NFKBIA and ARG1 as hubs in the networks and 3 groups of interacting key node CpGs and peanut severity genes encompassing immune response, chemotaxis, and regulation of macroautophagy. In addition, we found that gene expression of PHACTR1 and ZNF121 causally mediates the association between methylation at corresponding CpGs and reaction severity, suggesting that methylation may serve as an anchor upon which gene expression modulates reaction severity., Conclusions: Our findings enhance current mechanistic understanding of the genetic and epigenetic architecture of reaction severity in peanut allergy., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Peanut allergy diagnosis relies on clinical reactivity to peanut supported by detection of specific IgE (sIgE) antibodies. Extract-based sIgE tests have low specificity, so component-resolved diagnostics may complement whole-extract testing., Methods: We systematically collected peanut allergen component data in seven databases and studied the diagnostic accuracy of peanut storage proteins (Arah1, 2, 3) and cross-reactive peanut proteins (Arah8 PR-10 and Arah9 lipid transfer protein) through meta-analyses. The systematic literature review included studies employing peanut components and oral food challenge (OFC) as reference standard in patients suspected of peanut allergy. Data for component sIgE at pre-defined detection thresholds were extracted and combined in random-effects bivariate meta-analyses. Risk of bias was assessed as recommended by Cochrane, with two additional quality items of importance for this review., Results: Nineteen eligible studies presented data suitable for meta-analysis. In cross-sectional pediatric studies, the pooled sensitivity of Arah2-sIgE at 0.35 kU A /L cutoff was 83.3% [95% CI 75.6, 88.9] and specificity in diagnosing objective peanut allergy was 83.6% [95% CI 77.4, 88.4]. Compared with 0.1 and 1.0 kU A /L, this threshold provided the best diagnostic accuracy. At 0.35 kU A /L, Arah1 and Arah3 had comparable specificity (86.0% and 88.0%, respectively) but significantly lower sensitivity compared with Arah2 (37.0% and 39.1%, respectively; P < .05)., Conclusion: sIgE to Arah2 can enhance the certainty of diagnosis and reduce the number of OFC necessary to rule out clinical peanut allergy in unclear cases., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all individuals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass cytometry to define the circulating immune cell signatures associated with sensitized tolerance and clinical allergy to peanut in the first year of life. Key features of clinical peanut allergic are increased frequency of activated B cells (CD19 hi HLADR hi ), overproduction of TNFα and increased frequency of peanut-specific memory CD4 T cells. Infants with sensitized tolerance display reduced frequency but hyper-responsive naive CD4 T cells and an increased frequency of plasmacytoid dendritic cells. This work demonstrates the utility and power of high-dimensional mass cytometry analysis to interrogate the cellular interactions that are associated with allergic sensitization and clinical food allergy in the first year of life.

Introduction : Peanut allergy has continued to increase in prevalence and despite efforts to prevent the allergy with early peanut introduction, treatments for those already with the allergy have been lacking. While the physical effects of peanut allergy have been well known, what has more recently begun to be discussed are the broad psychosocial and financial implications that are also related to the allergy. Oral (OIT), epicutaneous (EPIT), and sublingual (SLIT) immunotherapy have been developed as potential treatments for peanut allergy. Areas covered : Pivotal clinical trials in OIT, EPIT, and SLIT from the past 10 years are reviewed in this manuscript. Peanut OIT has been shown to induce strong desensitization; however, side effects and safety of the treatment have remained a concern. Peanut EPIT has demonstrated a reassuring safety profile but with a more modest protective effect. Peanut SLIT has remained behind in development but recent studies have suggested a balance of desensitization, safety, and convenience. Expert opinion : There are no perfect treatments for peanut allergy and OIT, EPIT, and SLIT each has its unique pros and cons. Shared decision-making between patients and providers will be essential to achieve optimal care for patients with peanut allergy.

This article reviews research advances for sublingual and patch immunotherapy for food allergy with a focus on peanut allergy. Published studies on sublingual immunotherapy (SLIT) and epicutaneous immunotherapy (EPIT) were summarized in this review. Sublingual and epicutaneous methods have emerged as alternatives to oral immunotherapy. SLIT studies have shown modest desensitization with a robust safety profile. EPIT studies have high adherence rates, an excellent safety profile, and potential for desensitization in children. Advances in food immunotherapy with SLIT and EPIT studies have shown promise as viable alternatives to oral immunotherapy for treatment of patients with peanut food allergy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cumulative evidence shows that peanut oral immunotherapy (OIT) is effective at inducing desensitization through downregulation of effector pathways in the allergic reaction cascade; however, only a subset of patients achieve sustained unresponsiveness (remission), which requires redirection of the underlying allergic response toward tolerance. A recent meta-analysis of peanut OIT randomized trials found that OIT is associated with a threefold greater risk of anaphylaxis and twofold greater risk of epinephrine use than allergen avoidance. Strategies to reduce adverse events associated with OIT and improve the ability for OIT to induce sustained unresponsiveness are required to improve the benefit-risk of peanut OIT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Complete avoidance of peanut is difficult and accidental reactions are known to occur. Immunotherapy for peanut allergy is a potential treatment option being developed with the potential to reduce the risk of accidental reactions to peanut in the community. This article covers the epidemiology of unexpected allergic reactions to peanut, and outlines definitions of risk and risk reduction with quantitative risk assessment examples. Well-acknowledged future areas of research still exist, especially in the area of longer-term clinical trials or commercial data, which will strengthen the knowledge surrounding risk and potential options for risk reduction in those with peanut allergy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Peanut is among the most common of food allergies, and one of its allergens is Ara h 2. A previous study revealed that this allergen was recognized by serum immunoglobulin E (IgE) in over 90% of a peanut-allergic patient population. Enzymatic cross-linking is a popular processing method used to tailor food functionality, such as antigenicity., Result: The cross-linking reactions of Ara h 2 were catalyzed by polyphenol oxidase (PPO), and the relevant reaction sites were identified using mass spectrometry and StavroX software. Two pairs of intramolecular cross-linking peptides and two intermolecular cross-linking peptides were found. Intramolecular cross-linking was speculated to occur between ARG 131 (amino acids 116-131) and TYR 65 (amino acids 63-80) and between TYR 60 (amino acids 56-62) and ARG 92 (amino acids 92-102); the intermolecular cross-linking sites were ARG 31 with TYR 84 or TYR 89 and TYR 65 or TYR 72 with ARG 92 or ARG 102 . Three out of four cross-linking peptides were found in α-helices, and destruction of this secondary structure resulted in a loose tertiary structure. Although seven linear allergen epitopes were involved in cross-linking, the IgE binding capacity of protein changed slightly, while its sensitization potential decreased in mouse model., Conclusion: Exploring the structural change of Ara h 2 after cross-linking is beneficial in further understanding the influence of structure on sensitization. This result indicated the future possibility of precision processing on structure of proteins to improve their properties. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Objective: Low DNA sequence polymorphism despite enormous phenotypic variations in peanut indicates the possible role of epigenetic variations. An attempt was made to analyze genome-wide DNA methylation pattern and its influence on gene expression across 11 diverse genotypes of peanut., Results: The genotypes were subjected to bisulfite sequencing after 21 days of sowing (DAS). CHG regions showed the highest (30,537,376) DNA methylation followed by CpG (30,356,066) and CHH (15,993,361) across 11 genotypes. The B sub-genome exhibited higher DNA methylation sites (46,294,063) than the A sub-genome (30,415,166). Overall, the DNA methylation was more frequent in inter-genic regions than in the genic regions. The genes showing altered methylation and expression between the parent (TMV 2) and its EMS-derived mutant (TMV 2-NLM) were identified. Foliar disease resistant genotypes showed significant differential DNA methylation at 766 sites corresponding to 25 genes. Of them, two genes (Arahy.1XYC2X on chromosome 01 and Arahy.00Z2SH on chromosome 17) coding for senescence-associated protein showed differential expression with resistant genotypes recording higher fragments per kilobase of transcript per million mapped reads (FPKM) at their epialleles. Overall, the study indicated the variation in the DNA methylation pattern among the diverse genotypes of peanut and its influence of gene expression.

Enzymatic processing could reduce the allergenicity of peanut proteins while may lose the functional properties. Transglutaminase (TGase) is an enzyme for improving the functional properties of proteins/hydrolysates. No studies have been conducted on peanut hydrolysates that are crosslinked with TGase. In this study, allergenicity and functional properties of peanut protein hydrolysate cross-linked by TGase were tested. Papain, ficin and bromelain were selected out of eight food-grade enzymes for the kinetic analysis of peanut protein hydrolysis that lead to high reduction rate (K) of the IgE-binding property. Peanuts hydrolyzed by the three selected enzymes (200 AzU/g) were used for IgE binding, TGase-crosslinking and functional property characterization. After hydrolysis, the IgE-binding properties of the peanut soluble extracts were decreased (by 85%-95%); and functional properties were also decreased as compared to intact peanut protein extracts. The TGase crosslinked hydrolysates had similar IgE-binding properties to the un-crosslinked hydrolysates, but with higher functional properties., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Peanut allergy affects up to 2% of the general population and carries not only the risk of potentially life-threatening allergic reactions but also negatively impacts day to day life for patients and their families. Advances in knowledge in immunotherapy is providing families with options for proactive treatment. Objective: To examine the available data for oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) for peanut allergy. Methods: This review discusses recent studies that evaluated the safety and efficacy of OIT and EPIT to induce desensitization to peanut and identifies factors that should be considered when guiding families in treatment decisions. Results: Results of studies have demonstrated that immunotherapy can raise the threshold of peanut allergen to induce allergic reactions for many patients, thereby potentially reducing the risk for allergic reactions and decreasing the daily burden of peanut allergy. However, adverse reactions, which range from mild to severe, are possible with immunotherapy. Shared decision-making will be important to determine the best approach for peanut allergy management for each individual and his or her family. Conclusion: OIT and EPIT will offer patients and families more options for managing peanut allergies. Recent data from phase III studies on OIT and EPIT as well as real-world data on OIT advance the understanding of the efficacy and safety of these approaches. On-going studies aim to identify biomarkers to enhance patient selection criteria as well as develop additional therapeutic approaches.

Identification of allergenic IgE epitopes is instrumental for the development of novel diagnostic and prognostic methods in food allergy. In this work, we present the quantification and validation of a Bead-Based Epitope Assay (BBEA) that through multiplexing of epitopes and multiple sample processing enables completion of large experiments in a short period of time, using minimal quantities of patients' blood. Peptides that are uniquely coupled to beads are incubated with serum or plasma samples, and after a secondary fluorophore-labeled antibody is added, the level of fluorescence is quantified with a Luminex reader. The signal is then normalized and converted to epitope-specific antibody binding values. We show that the effect of technical artifacts, i.e. well position or reading order, is minimal; and batch effects - different individual microplate runs - can be easily estimated and eliminated from the data. Epitope-specific antibody binding quantified with BBEA is highly reliable, reproducible and has greater sensitivity of epitope detection compared to peptide microarrays. IgE directed at allergenic epitopes is a sensitive biomarker of food allergy and can be used to predict allergy severity and phenotypes; and quantification of the relationship between epitope-specific IgE and IgG4 can further improve our understanding of the immune mechanisms behind allergic sensitization.

Tomato spotted wilt virus (TSWV) is a devastating disease to peanut growers in the South-eastern region of the United States. Newly released peanut cultivars in recent years are crucial as they have some levels of resistance to TSWV. One mapping population of recombinant inbred line (RIL) used in this study was derived from peanut lines of SunOleic 97R and NC94022. A whole genome re-sequencing approach was used to sequence these two parents and 140 RILs. A recombination bin-based genetic map was constructed, with 5,816 bins and 20 linkage groups covering a total length of 2004 cM. Using this map, we identified three QTLs which were colocalized on chromosome A01. One QTL had the largest effect of 36.51% to the phenotypic variation and encompassed 89.5 Kb genomic region. This genome region had a cluster of genes, which code for chitinases, strictosidine synthase-like, and NBS-LRR proteins. SNPs linked to this QTL were used to develop Kompetitive allele specific PCR (KASP) markers, and the validated KASP markers showed expected segregation of alleles coming from resistant and susceptible parents within the population. Therefore, this bin-map and QTL associated with TSWV resistance made it possible for functional gene mapping, map-based cloning, and marker-assisted breeding. This study identified the highest number of SNP makers and demonstrated recombination bin-based map for QTL identification in peanut. The chitinase gene clusters and NBS-LRR disease resistance genes in this region suggest the possible involvement in peanut resistance to TSWV.

Background: For patients with peanut allergy, there are currently no methods to predict who will develop sustained unresponsiveness (SU) after oral immunotherapy (OIT)., Objective: Assess IgE binding to peanut (PN), Ara h 2, and specific linear epitopes of Ara h 2 as predictors of the important clinical parameters: eliciting dose threshold and attainment of SU following OIT., Methods: Samples and clinical data were collected from children undergoing OIT. PN- and Ara h 2-sIgE were quantified by ImmunoCAP ® . IgE binding to linear peptides of Ara h 2 and Ara h 6 was measured with peptide microarrays., Results: Values of PN-sIgE correlated with eliciting dose (P = .001) and with a higher likelihood of achieving SU (P < .0001), but these relationships were lost at higher values for PN-sIgE (≥14 kIU for eliciting dose and ≥35 kIU/L for SU). In subjects with PN-sIgE ≥ 14 kIU/L, binding of IgE to epitopes 5 and 6 of Ara h 2 was associated with a lower eliciting dose at baseline challenge (P < .001; P c  < .02). In subjects with PN-sIgE ≥ 35 kIU/L, a combined model of IgE binding to epitopes 1, 5 and 6 with PN-sIgE was highly predictive of attainment of SU (AUC of 0.86; P = .0067)., Conclusion: In young patients with peanut allergy, measurement of PN-sIgE and IgE binding to specific linear epitopes of Ara h 2 in baseline samples may allow stratification of patients regarding sensitivity to challenge and outcome of OIT., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Peanut allergy is usually lifelong and accidental exposure impose formidable risk. The aim of this study was to assess the capacity of peanut proteins complexed to polyphenol extracts to reduce allergic response in C3H/HeJ mice. Mice were sensitized to peanut flour followed by exposure to amino acid diets fortified with peanut protein-polyphenol aggregates of either with low (15%; w/w) or high (40%; w/w) complexation ratios of blueberry (BB-Low and BB-High) and cranberry (CB-Low and CB-High) extracts. Treatment groups on diets with high complexation ratios of blueberry and cranberry aggregates showed significant reduction in peanut specific plasma Immunoglobulin E (IgE). Western blot analysis of spleen lysates showed CD63 protein expression was reduced in a dose-dependent manner in blueberry and cranberry complexed peanut protein supplemented diet groups. Our results demonstrate for the first time that complexation of polyphenols to peanut flour can potentially lower plasma IgE of peanut-sensitized C3H/HeJ mice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The prevalence of peanut allergies has escalated over the last 20 years, yet there are no FDA approved treatments for peanut allergies. In this study we evaluated the potential of microneedles to deliver peanut protein extract (PE) into skin and assessed if the ensuing immune responses could desensitize mice that were sensitized to peanuts. Peanut sensitized mice were either treated through cutaneous immunotherapy using PE-coated microneedles or not treated, and then orally challenged with PE. After oral challenge, the clinical symptoms of peanut-induced anaphylaxis were significantly lower in the microneedle treated mice as compared to untreated mice, and this was accompanied by down-regulation of systemic anaphylaxis mediators such as histamine and mast cell protease-1 (MCPT-1) in the microneedles treated group. Overall, there was an up-regulation of Th1 cytokines (IL-2 and IFN-γ) as compared to Th2 cytokines (IL-4 and IL-5) in splenocyte culture supernatants of the microneedle treated group as compared to untreated group, suggesting that microneedles promoted immune modulation towards the Th1 pathway. Furthermore, mice treated with PE-coated microneedles were observed to retain integrity of their small intestine villi and had reduced eosinophilic infiltration as compared to the untreated but peanut sensitized mice, which further confirmed the desensitization capability of peanut cutaneous immunotherapy using coated microneedles. Thus, our current study represents a novel minimally invasive microneedle based cutaneous immunotherapy, which may provide a novel route of desensitization for the treatment of peanut allergies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose of Review: This review summarizes the evidence leading towards the development of new guidelines that recommend early introduction of peanut to prevent the development of peanut allergy. It also reviews the current understanding of challenges faced with implementation of these recommendations on a widespread basis., Recent Findings: Prior recommendations to avoid feeding allergenic foods to infants have been updated and reversed. This paradigm shift in advice has created an opportunity on a population level to try and halt the recent increase in prevalence of peanut allergy. However, challenges with implementation of these new guidelines exist in many areas. While evidence supports the early introduction of peanut to prevent allergy development, the application and challenges faced with these recommendations are not fully understood. Persistent efforts from pediatricians and allergists, as well as acceptance from parents, will be necessary in order to make a significant impact on the prevalence of peanut allergy.

Background: Prognostication of peanut allergy (PNA) is relevant for early interventions. We aimed to determine baseline parameters associated with the development of PNA in 3- to 15-month-olds with likely egg and/or milk allergy, and/or moderate to severe atopic dermatitis (AD) and a positive egg/milk skin prick test (SPT), but no known PNA., Methods: The primary endpoint was PNA [confirmed/convincing diagnosis or last classified as serologic PNA (<2 years, ≥5 kUA/L, otherwise ≥14 kUA/L, peanut IgE)] among 511 participants (median follow-up, 7.3 years). Associations were explored with univariate logistic regression; factors with P < 0.15 were analyzed by stepwise multiple logistic regression, using data stratified by PNA status and randomly assigned to development and validation datasets., Results: 205/511 (40.1%) had PNA. Univariate factors associated with PNA (P < 0.01) included increased AD severity, larger egg and peanut SPT, greater egg, milk, peanut, Ara h1-h3 IgE, higher peanut IgG and IgG4, and increased pregnancy peanut consumption. P-values were between 0.01 and 0.05 for younger age, non-white race, lack of breastfeeding, and increased lactation peanut consumption. Using a development dataset, the multivariate model identified younger age at enrollment, greater peanut and Ara h2 IgE, and lack of breastfeeding as prognosticators. The final model predicted 79% in the development and 75% in the validation dataset (AUC = 0.83 for both). Models using stricter or less strict PNA criteria both found Ara h2 as predictive., Conclusions: Key factors associated with PNA in this high-risk population included lack of breastfeeding, age, and greater Ara h2 and peanut-specific IgE, which can be used to prognosticate outcomes., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The peanut allergens Ara h 2, h 6, and h 7 are potent allergens and can trigger severe reactions. Ara h 7 consists of three isoforms differing in their ability to induce basophil degranulation, whereas the ability of Ara h 7.0201 is comparable to Ara h 2 and 6 as shown in previous literature., Objective: To identify linear epitopes of Ara h 7.0101, Ara h 7.0201 and Ara h 7.0301 recognized by IgE and IgG4 from patients sensitized to Ara h 7 and to investigate their potential to elucidate divergent abilities of the Ara h 7 isoforms in inducing basophil activation., Methods: Linear epitopes recognized by IgE and IgG4 were mapped by peptide microarray analysis containing 15-mer peptides of Ara h 2.0201, 6, 7.0101, 7.0201 and 7.0301 and 39 peanut allergic patients sensitized to Ara h 7 (discovery). For validation, 20-mer peptides containing the minimal epitope and surrounding amino acids were incubated with 25 sensitized patients and 10 controls (validation)., Results: Three out of 14 linear epitopes were unique for each isoform (Ara h 7.0101: aa 97-109; Ara h 7.0201: aa 122-133; Ara h 7.0301: aa 65-74) but scarcely recognized by IgE. The main linear IgE epitope (aa 51-57) located in the long flexible loop of all Ara h 7 isoforms was bound by antibodies from 31% of the patients (discovery and validation cohort). Regarding IgG4, 55% of the patients recognized an epitope present on all isoforms (aa 55-65), whereas epitope aa 129-137, only present on Ara h 7.0101/0.0301, was recognized by 38% of the patients. Recognition was highly individual, although 20% of the patients recognized any linear epitope neither by IgE nor by IgG4 despite a low mean z-score of ≥ 1.7. Remarkably, only 50% of the patients recognized one or more epitopes by IgE., Conclusion & Clinical Relevance: Ara h 7 isoforms share many linear epitopes being easily accessible for antibody binding. Unique epitopes, essential to elucidate divergent potencies, were scarcely recognized, suggesting a crucial involvement of conformational epitopes., (© 2019 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Randomized controlled trials demonstrate that timely introduction of peanut to infants reduces the risk of peanut allergy. However, much debate remains regarding how to best achieve earlier peanut introduction at the population level. Our previous study in 2007-2011 (HealthNuts, n = 5300) indicated that few infants were consuming peanut in the first year. Australian infant feeding guidelines were updated in 2016 to recommend introducing peanut before 12 months for all infants. There were no data available on the subsequent effect on peanut introduction or peanut reactions., Objective: We sought to assess the consequences of a nonscreening approach to allergenic food introduction in a population-based sample of infants in their first year of life., Methods: EarlyNuts is a population-based, cross-sectional study of 12-month-old infants in Melbourne, Australia, recruited by using an identical sampling frame and methods to HealthNuts (72% response rate vs 73% response rate in HealthNuts). We report here on the first 860 participants recruited between November 2016 and October 2018., Results: Most infants (88.6%; 95% CI, 86.1% to 90.7%) had introduced peanut by 12 months (median age, 6 months), an increase from 28.4% (95% CI, 27.2% to 29.7%) in the HealthNuts study. By 12 months, the majority of these (76.4%) had consumed peanut more than 4 times, and 28% were eating peanut more than once per week. Preliminary results on parent-reported reactions show that 4.0% of those consuming peanut by 12 months had possible IgE-mediated reactions., Conclusions: There has been a striking shift toward earlier peanut introduction, with a 3-fold increase in peanut introduction by age 1 year in 2018 compared with 2007-2011., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)