Current perspectives on peanut allergy.
Peanut allergy is increasingly prevalent and for most patients is a life-long condition, with the potential to cause life-threatening reactions. Accurate diagnosis and appropriate management are essential to minimise risks due to accidental peanut exposure. Current management strategies focus on strict allergen avoidance and access to emergency medicines to treat potential reactions; however, active approaches are an area of intense research. Promising new methods of food allergen immunotherapy are set to change the approach to managing peanut allergic patients in the near future.
Selection of universal peptide biomarkers for the detection of the allergen hazelnut in food trough a comprehensive, high resolution mass spectrometric (HRMS) based approach.
The interest of using LC-MS/MS as a method for detection of allergens in food is growing. In such methods, peptides are used as biomarkers for the detection and quantification of the allergens. The selection of good biomarker peptides is of high importance to develop a specific, universal and sensitive method. Biomarkers should, for example, be robust to food processing. To evaluate robustness, test material incurred with hazelnut having undergone different food processing techniques was produced. Proteins of these materials were extracted, digested and further analyzed using HRMS. After peptide identification, selection was carried out using several criteria such as hazelnut specificity and amino acid composition. Further selection was done by comparing peptide MS intensities in the different food matrices. Only peptides showing processing robustness were retained. Eventually, eight peptides coming from three major hazelnut proteins were selected as the best biomarkers for hazelnut detection in processed foods.
Prevention of Non-peanut Food Allergies.
Purpose of review: The purpose of this review article is to discuss the recent literature around methods of prevention of food allergies other than peanut allergy. Recent findings: While the most robust data to date exists for peanut, there are emerging studies suggesting a beneficial effect to early introduction of cooked egg, and cow's milk as well. While the literature is sparse for other allergens such as tree nuts, finned fish, and shellfish, the mechanism of sensitization is thought to be the same and no study to date has demonstrated a harm with allergenic introduction in the 4-6 months of age window (nor has there been level 1 evidence of benefit to delay of such allergens). This strategy is safe, and pre-emptive testing is not required prior to allergenic solid introduction. All allergenic solids should be introduced at around 6, but not before 4, months of age in infants at high risk.
Sustained Successful Peanut Oral Immunotherapy Associated with Low Basophil Activation and Peanut-Specific IgE.
Background: Oral immunotherapy (OIT) can successfully desensitize many peanut allergic subjects, but clinical tolerance diminishes over time upon discontinuation, or low dose maintenance, of peanut. Therefore, in order to improve the efficacy and sustainability of such therapy, we sought to identify biomarkers and clinical tools that can predict therapeutic outcomes and monitor treatment responses. Objective: We evaluated whether basophil activation in whole blood, and plasma levels of peanut-specific immunoglobulins, are useful biomarkers for peanut OIT. Methods: We longitudinally measured, before, during and after OIT, basophil activation in whole blood ex vivo in response to peanut stimulation, and peanut-specific IgE and IgG4, in a large, single-site, double-blind, randomized, placebo-controlled, phase 2 peanut OIT study. We compared basophil responsiveness and peanut specific immunoglobulins between those who were clinically reactive vs. tolerant to peanut oral challenges. Results: Peanut OIT significantly decreased basophil activation, peanut-specific, Ara h 1, Ara h 2 and Ara h 3 IgEs, and sIgE/total IgE, but increased sIgG4/sIgE. Participants who became reactive to 4 g of peanut 13 weeks off active OIT exhibited higher peanut-induced basophil activation ex vivo and higher peanut-specific IgEs and sIgE/total IgE, but lower sIgG4/sIgE. Notably, participants entering the study with low basophil responsiveness were more likely to achieve treatment success. Substantial suppression of basophil activation was required to maintain long-term clinical tolerance after peanut OIT. Conclusion: Assessments of peanut-specific basophil activation and peanut-specific immunoglobulins can help to predict treatment outcomes, and to differentiate transient desensitization vs. sustained unresponsiveness after OIT.
Accuracy of component‐resolved diagnostics in peanut allergy: systematic literature review and meta‐analysis.
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 kUA /L cut-off 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 kUA /L, this threshold provided the best diagnostic accuracy. At 0.35 kUA /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<0.05). Conclusion: sIgE to Ara h 2 can enhance the certainty of diagnosis and reduce the number of OFC necessary to rule out clinical peanut allergy in unclear cases.
Determining Levers of Cost-effectiveness for Screening Infants at High Risk for Peanut Sensitization Before Early Peanut Introduction.
Importance: Early peanut introduction reduces the risk of developing peanut allergy, especially in high-risk infants. Current US recommendations endorse screening but are not cost-effective relative to other international strategies. Objective: To identify scenarios in which current early peanut introduction guidelines would be cost-effective. Design, setting, and participants: This simulation/cohort economic evaluation used microsimulations and cohort analyses in a Markov model to evaluate the cost-effectiveness of early peanut introduction with and without peanut skin prick test (SPT) screening in high-risk infants during an 80-year horizon from a societal perspective. Data were analyzed from April to May 2019. Exposures: High-risk infants with early-onset eczema and/or egg allergy underwent early peanut introduction with and without peanut SPT screening (100 000 infants per treatment strategy) using a dichotomous 8-mm SPT cutoff value (stipulated in the current US guideline). Main outcomes and measures: Cost, quality-adjusted life-years (QALYs), net monetary benefit, peanut allergic reactions, severe allergic reactions, and deaths due to peanut allergy. Results: In the simulated cohort of 200 000 infants and using the base case during the model horizon, a no-screening approach had lower mean (SD) costs ($13 449 [$38 163] vs $15 279 [$38 995]) and higher mean (SD) gain in QALYs (29.25 [3.28] vs 29.23 [3.30]) vs screening but resulted in more allergic reactions (mean [SD], 1.07 [3.15] vs 1.01 [3.02]), severe allergic reactions (mean [SD], 0.53 [1.66] vs 0.52 [1.62]), and anaphylaxis involving cardiorespiratory compromise (mean [SD], 0.50 [1.59] vs 0.49 [1.47]) per individual. In deterministic SPT sensitivity analyses at base-case sensitivity and specificity rates, screening could be cost-effective at a high disutility rate (the negative effect of a food allergic reaction) (76-148 days of life traded) for an at-home vs in-clinic reaction in combination with high baseline peanut allergy prevalence among infants at high risk for peanut allergy and not yet exposed to peanuts. If an equivalent rate and disutility of accidental and index anaphylaxis was assumed and the 8-mm SPT cutoff had 0.85 sensitivity and 0.98 specificity, screening was cost-effective at a peanut allergy prevalence of 36%. Conclusions and relevance: The results of this study suggest that the current screening approach to early peanut introduction could be cost-effective at a particular health utility for an in-clinic reaction, SPT sensitivity and specificity, and high baseline peanut allergy prevalence among high-risk infants. However, such conditions are unlikely to be plausible to realistically achieve. Further research is needed to define the health state utility associated with reaction location.
Dual transcriptomic and epigenomic study of reaction severity in peanut allergic children.
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: 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. 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 three groups of interacting key node CpGs and peanut severity genes encompassing immune response, chemotaxis, and regulation of macroautophagy. Additionally, we found that gene expression of PHACTR1 and ZNF121 causally mediate 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.
Evaluation of the epidemiology of peanut allergy in the United Kingdom.
Aims: To describe the epidemiology of peanut allergy (PA) in the UK over the last three decades. Methods: PA patients were identified from the Clinical Practice Research Datalink between 1987 and 2015. Incidence and prevalence of PA were compared between 2000 and 2015. Prevalence and relative risk (RR) of atopic comorbidities, anaphylaxis, adrenaline prescriptions versus matched controls were calculated. Results: Point prevalence of PA in the entire population and those <18 years increased from 31 to 202 and 116 to 635 per 100,000, respectively, between 2000 and 2015. Incidence increased from 8.6 to 18.2 per 100,000. Incidence in 2015 was 105 cases per 100,000 aged 0-4 years versus 13.4 per 100,000 aged 5+ years. Anaphylactic events affected 1.2% of the cases and 0.007% of the controls. The rate of adrenaline prescriptions was 5,910 per 100,000 person-years for PA patients. RRs for asthma, eczema and allergic rhinitis in PA patients versus controls were 4.5 (95% CI 4.2-4.8), 3.2 (3.1-3.4) and 2.6 (2.4-3.0), respectively. Conclusions: The prevalence and incidence of PA increased markedly over the study period. PA was associated with atopic conditions and anaphylaxis. PA patients had increased adrenaline prescriptions.
Undeclared allergens in imported packaged food for retail in Australia.
The Australia New Zealand Food Standards Code (the Code) requires a declaration of the presence of 11 different allergens made through the label on a food product. Most food recalls in Australia are now due to undeclared allergens. This survey determined the extent of undeclared allergens in imported food products on the Asian retail market in Australia. A total of 50 imported packaged foods were selectively purchased from local Asian grocery retail stores in Melbourne and the presence of undeclared gluten, milk, peanut and egg determined. Analysis was performed using commercial enzyme-linked immunosorbent assay (ELISA) (R-Biopharm). Thirty-seven undeclared allergens (gluten n = 12, milk n = 12, peanut n = 6, and egg n = 7) were detected in 23 of the 50 products analysed (46%), with 18% containing multiple undeclared allergens. The high number of undeclared allergens is alarming and in line with the increasing number of food recalls and anaphylaxis recorded in Australia.
Peanut Oral Immunotherapy: State of the Art.
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.