Recent developments and highlights in food allergy.
The achievement of long lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests like the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food allergic individuals with distinct mechanistic features. Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continue to inform the understanding of natural tolerance development. Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit. More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL4 and IL13, or IgE may help to achieve that.
Phenotypical characterization of tree nuts and peanut allergies in east Mediterranean children.
INTRODUCTION/OBJECTIVES: The characteristics of tree nuts (TNs) and peanut (PN) allergies vary in different regions of the world. We aim to identify the characteristics of TNs/PN allergies in Turkish children. PATIENTS AND METHODS: A total of 227 children [4.8 (3.2-6.8) years] with TN and/or PN allergies were included. The phenotypical features of TNs/PN allergic children and the risk factors for multiple TNs/PN allergies were evaluated. RESULTS: Allergy to TNs/PN developed at a median age of 12.0 (10.0-18.0) months. The most common TNs/PN responsible for food allergies were the hazelnut (63.9%) and the pistachio (54.6%). Of TNs/PN allergic children, 54.2% experienced reactions with at least two types of . Current ages 6-10 years [OR:2.455, 95% CI:1.255-4.852, p=0.009] and family history of atopy [OR:2.156, 95% CI:1.182-3.932, p=0.012] were the risk factors for multiple TNs/PN allergies. Most of the patients with cashew nut and pistachio allergies exhibited co-sensitization and co-allergy to both of these TNs/PN. Although the rarest TNs/PN allergy was seen with almond, the possibility of allergy to other TNs or PN was highly increased in the patients with almond allergy compared to other TNs/PN. CONCLUSIONS: Children with TNs/PN allergy living in an East Mediterranean region differ from the counterparts living in Western countries by an earlier age of onset of the TNs/PN allergy symptoms, increasing possibility to have multiple TNs/PN allergy at older ages, and different spectrum of TN/PN allergies (hazelnut followed by pistachio/cashew) that all indicate the consumption habits which are important determinants of TN/PN allergy development.
Moving Past “Avoid All Nuts”: Individualizing Management of Children with Peanut/Tree Nut Allergies.
It has been common practice to tell patients with allergy to peanut or tree nuts to avoid all nuts. Evidence that unnecessary avoidance of peanuts and eggs is associated with increased risk for developing anaphylaxis to those foods has changed how allergists view previous recommendations to avoid foods that have not caused a reaction. In the absence of evidence, collaborative decision making between clinicians and families should be used to decide whether to avoid tree nuts and how to safely introduce tree nuts into the diet. This article discusses the options for introducing tree nuts to children with peanut allergy.
High-resolution mass spectrometry-based selection of peanut peptide biomarkers considering food processing and market type variation.
To protect allergic patients and guarantee correct food labeling, robust, specific and sensitive detection methods are urgently needed. Mass spectrometry (MS)-based methods could overcome the limitations of current detection techniques. The first step in the development of an MS-based method is the identification of biomarkers, which are, in the case of food allergens, peptides. Here, we implemented a strategy to identify the most salient peptide biomarkers in peanuts. Processed peanut matrices were prepared and analyzed using an untargeted approach via high-resolution MS. More than 300 identified peptides were further filtered using selection criteria to strengthen the analytical performance of a future, routine quantitative method. The resulting 16 peptides are robust to food processing, specific to peanuts, and satisfy sequence-based criteria. The aspect of multiple protein isoforms is also considered in the selection tree, an aspect that is essential for a quantitative method's robustness but seldom, if ever, considered.
A cashew specific monoclonal antibody recognizing the small subunit of Ana o 3.
Food allergies represent a substantial medical liability and preventing accidental exposure to food allergens requires constant attention. Allergic reaction to cashew nuts is frequently serious, and the small 2S albumin, Ana o 3, is an immuno-dominant cashew allergen. Ana o 3 is composed of five alpha helices, contains 2 subunits linked by cysteine disulfide bonds, and remains soluble even after extensive heating of cashew nuts. The stability and solubility properties of Ana o 3 make it an excellent target for diagnostic and detection methods and tools. In this work, a monoclonal antibody, designated 2H5, aimed at amino acids 39-54 within helices I and II of the small subunit of Ana o 3 was developed that recognizes both recombinant and native Ana o 3 and is cashew specific in ELISA experiments. The KD against the targeted amino-acid sequence was found to be approximately 7.0 × 10-6 mg/ml (3.3 nM), while the KD against the native protein was found to be approximately 1.2 × 10-3 mg/ml (92 nM). The 2H5 monoclonal anti-Ana o 3 antibody can distinguish between native and recombinant proteins and represents a useful reagent for the study of antibody cashew-allergen interactions and may enable the development of cashew-specific diagnostic tools that can be used to prevent accidental cashew allergen exposures.
Oral Immunotherapy for Multiple Foods in a Pediatric Allergy Clinic Setting.
BACKGROUND: The rising incidence of pediatric food allergy results in significant health care burden and family stress. Oral immunotherapy (OIT) has been shown to induce tolerance to peanut, milk and egg. OIT for other foods, particularly multiple foods simultaneously, has not been thoroughly studied. OBJECTIVE: To summarize our experience with OIT for multiple foods in a pediatric allergy clinic setting. METHODS: Medical records were reviewed for patients undergoing OIT for multiple foods. Methods and outcomes of OIT were summarized. Outcomes were analyzed for correlation with baseline food allergen skin prick tests (SPT) and specific IgE (sIgE) results. RESULTS: Forty-five patients aged 1.5-18 years undertook OIT for up to 12 foods, including peanut, tree nuts, seeds, legumes and egg. At the time of review, 35 patients were on daily maintenance dosing, 4 had completed OIT and were continuing to eat their foods 3 times weekly, and 6 had stopped OIT due to anxiety, inconvenience or allergy symptoms. 49% of patients had reactions during the updosing process, mostly oral itching (33%), perioral hives (40%) and abdominal pain (35%). There was no correlation of baseline SPT and sIgE with reaction threshold for baseline food challenge, lowest dose causing reactions during updosing, or time to reach maintenance. Higher baseline sIgE, but not baseline SPT, was associated with increased number of allergic reactions during OIT. Baseline SPT correlated with stopping OIT. CONCLUSION: A similar approach to that used for peanut OIT can be taken for non-peanut foods, and for multiple foods simultaneously. High baseline allergy test results are not a contraindication to OIT.
Peanut allergen reduction and functional property improvement by means of enzymatic hydrolysis and transglutaminase crosslinking.
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.
Quantitative and kinetic analyses of peanut allergens as affected by food processing.
Peanuts contain four major allergens with differences in allergenic potency. Thermal processing can influence the allergenic properties of peanuts. Until now, a kinetic model has not been reported to assess the changes of soluble allergen (extracted from processed peanuts) content as affected by various thermal processing methods. Our objective is to characterize the reaction kinetics of the thermal processing methods, including wet processing (boiling with/without high-pressure, steaming with/without high-pressure), deep-frying and dry processing (microwaving and roasting) using five time intervals. The relationships between processing time and extractable major allergen content could be explained by a simple linear regression kinetic model (except high-pressure steaming). Among all the methods with optimal processing point, frying for 6 min had a relatively lower IgE binding (linear epitopes) ratio, possibly due to the processing conditions, which caused break down, cross-linking and aggregation of Ara h 2, and a relatively lower solubility.
Predictive value of peanut skin prick test, specific IgE in peanut-sensitized children in Singapore.
BACKGROUND: The predictive decision points for both peanut skin prick test (SPT) wheal size and serum IgE concentrations, in peanut-sensitized children, have not been evaluated in Singapore. OBJECTIVE: We aim to derive clinically useful predictive decision points to be used for risk stratification of oral food challenge (OFC) in peanut-sensitized patients. METHODS: Patients with a positive SPT to peanut, performed during a 4-year period between 2012 and 2016, were included in a retrospective chart review. The patients were assessed for their peanut allergy status based on a convincing clinical history. Their first SPT and serum IgE results done at presentation to our centre were used. RESULTS: There were 269 patients with a clinical diagnosis of peanut allergy based on recent immediate reaction to peanut and 59 patients whom were tolerating peanuts regularly. There were 251 patients sensitized to peanut, without prior known peanut exposure. A wheal size of ≥8 mm and a peanut-specific IgE of ≥6 kU/L each provided for a 95% positive predictive value of clinical reaction to peanuts; the larger the wheal size on SPT, the higher the probability. CONCLUSION: The cutoff values derived in this study can help clinicians in the risk assessment of OFC in peanut-sensitized patients. Prospective studies using OFCs for the diagnosis of peanut allergy are needed to confirm the diagnostic performance of these tests in predicting OFC outcomes.
Allergen components in diagnosing childhood hazelnut allergy: systematic literature review and meta‐analysis
BACKGROUND: Hazelnut-specific IgE antibodies (sIgE) in serum support the diagnosis of hazelnut allergy, but extract-based tests have low diagnostic specificity, commonly leading to over-diagnosis. Measuring sensitization to individual allergen components may enhance the diagnosis of hazelnut allergy. We systematically examined data on diagnostic accuracy of sIgE to commercially available hazelnut components to compare their individual contributions in diagnosing hazelnut allergy. METHODS: Seven databases were searched for diagnostic studies on patients suspected of having hazelnut allergy. Studies employing component-specific IgE testing on patients whose final diagnosis was determined by oral food challenges were included in the meta-analysis. Study quality was assessed as recommended by Cochrane. RESULTS: Seven cross-sectional studies and one case-control study were identified, seven presenting data on children (N=635), and one on a mixed age population. Overall, the diagnostic accuracies of sIgE to both Cor a 9 and Cor a 14 were significantly higher than for Cor a 1-sIgE (p<0.05). In children, the specificity of Cor a 14-sIgE at 0.35 kUA /L cut-off was 81.7% [95% CI 77.1, 85.6], 67.3% [60.3, 73.6] for Cor a 9-sIgE. The specificities for Cor a 1-sIgE and hazelnut-sIgE were 22.5% [7.4, 51.2] and 10.8% [3.4, 29.8], respectively. The sensitivity of Cor a 1-sIgE (60.2% [46.9, 72.2]) was lower than for hazelnut extract-sIgE (95.7% [88.7, 98.5]), while their specificities did not differ significantly. CONCLUSION: sIgE to Cor a 14 and Cor a 9 hazelnut storage proteins increase diagnostic specificity in assessing hazelnut allergy in children. Combined use of hazelnut extract and hazelnut storage proteins may improve diagnostic value.