Hazelnut Allergy.
Background and Objectives: Hazelnuts are frequently involved in IgE-mediated reactions and represent the main culprit of nut allergy in Europe. The clinical presentation varies from mild symptoms limited to the oropharynx [oral allergy syndrome (OAS)], due to the cross-reaction with homologues in pollen allergens and more severe events caused by the primary sensitization to highly stable molecules contained in hazelnuts. The aim of this review is to summarize the most relevant concepts in the field of hazelnut allergy and to provide a practical approach useful in the clinical practice Materials and Methods: References were identified by PubMed searches dating from January 2000 up to November 2020 using the search terms: "component resolved diagnosis" and "Hazelnut allergy. Results: The storage proteins Cor a 9 and Cor a 14 resulted highly specific for primary hazelnut allergy and strongly associated with severe reactions, while the cross reactive Cor a 1, an homolog of the birch Bet v1, were related to OAS. Any cut-off has shown a specificity and sensitivity pattern as high as to replace the oral food challenge (OFC), which still remains the gold standard in the diagnosis of hazelnut allergy. To date there is still no definitive treatment. Hazelnut free-diet and treatment of symptoms with emergency management, including the prescription of auto-injective epinephrine, still represent the main approach. Oral allergen immunotherapy (AIT) appears a promising therapeutic strategy and the definition of individual clinical threshold would be useful for sensitized individuals, caregivers, and physicians to reduce social limitation, anxiety, and better manage food allergy. Conclusions: An accurate diagnostic work-up including clinical history, in vivo and in vitro test including component resolved diagnosis and OFC are essential to confirm the diagnosis, to assess the risk of a severe reaction, and to prescribe an adequate diet and treatment.
Epitope mapping of the major allergen 2S albumin from pine nut.
The epitopes of the major allergen of pine nut, Pin p 1, were analyzed using a peptide library and sera from patients with clinical allergy to pine nut in order to deepen into the allergenic characteristics of Pin p 1. Analyses of epitope similarities and epitopes location in a 3D-model were also performed. Results showed that three main regions of Pin p 1 containing 5 epitopes were recognized by patient sera IgE. The epitopes of Pin p 1 had important similarities with epitopes of allergenic 2S albumins from peanut (Ara h 2 and 6) and Brazil nut (Ber e 1). The epitopes of Pin p 1 were found in α-helices and coils in the 3D protein structure. Interestingly, all epitopes were found to be well-exposed in the protein surface, which suggests facile access for IgE-binding to the structure of Pin p 1 which is known to be highly resistant.
The accuracy of diagnostic testing in determining tree nut allergy: a systematic review.
Background: Food allergy is most accurately diagnosed by a formal oral food challenge however it is time and labor intensive, risks the individual to severe reaction and access is often a limiting step in the diagnostic process. This is compounded for tree nut allergy diagnosis as several oral food challenges may be required to determine allergy status to each individual tree nut. Accurate diagnosis using minimally invasive diagnostic tests in predicting clinical tree nut allergy is important to correctly identify those with potentially life-threatening reactions, and to efficiently and safely tailor nut avoidance to only those nuts deemed allergic to enable less restricted diets and increased food choices for food allergic individuals.
Objective: To conduct a systematic review on the diagnostic capacity of clinical tests (Skin Prick Test (SPT), specific IgE, Component Resolved Diagnostics (CRD), Basophil Activation Test (BAT)) to determine oral food challenge proven or clinical tree nut allergy.
Methods: We searched four electronic databases (OVID Medline, Embase, Cochrane library and PubMed) until May 2020. Eligible studies were categorized by type of tree nut, and diagnostic test.
Results: 27 studies assessed diagnostic accuracy to a specific tree nut. Overall, the accuracy of diagnostic testing was only reasonable, with 95% positive predictive values established in a small number of tree nuts. Cashew has best diagnostic accuracy, with the cashew component Ana o 3 being most predictive. At the other end of the spectrum, diagnostic testing of almond is poor and of limited clinical use.
Conclusion: The systematic review highlights the limitations of our current diagnostic tools for tree nut allergy and highlights further areas for research. The uni-directionality of cross-reactivity between cashew/pistachio and walnut/pecan is described and can aid diagnosis. Using diagnostic algorithms such as those demonstrated for walnut/pecan and cashew/pistachio allergy may achieve greater diagnostic accuracy and reduced number of OFCs.
Discovery based high resolution MS/MS analysis for selection of allergen markers in chocolate and broth powder matrices.
Peptide marker identification is an important step in development of a mass spectrometry method for multiple allergen detection, since specificity, robustness and sensitivity of the overall analytical method will depend on the reliability of the proteotypic peptides. As part of the development of a multi-analyte reference method, discovery analysis of two incurred food matrices has been undertaken to select the most reliable peptide markers. Six allergenic ingredients (milk, egg, peanut, soybean, hazelnut, and almond) were incurred into either chocolate or broth powder matrix. Different conditions of protein extraction and purification were tested and the tryptic peptide pools were analysed by untargeted high resolution tandem mass spectrometry and the resulting fragmentation spectra were processed via a commercial software for sequence identification. The analysis performed on incurred foods provides both a prototype effective and straightforward sample preparation protocol and delivers reliable peptides to be included in a standardized selected reaction monitoring method.
Basophil activation test reduces oral food challenges to nuts and sesame.
Background: Nut allergic patients are often IgE sensitized to other nuts/seeds and need multiple oral food challenges (OFCs) before the safe nuts can be introduced in the diet. However, OFCs are time-consuming and risky procedures.
Objective: To assess the utility of the basophil activation test (BAT) to predict the allergic status and reduce the need for an OFC in children with 1 or more nut or seed allergies.
Methods: Participants in the Pronuts study recruited at the Geneva and the London centers were tested on the BAT to hazelnut, cashew nut, sesame, almond, and peanut, Ara h 1, Ara h 2, Ara h 6, using FlowCAST, a commercially available BAT kit, and flow cytometry.
Results: The BAT to hazelnut, cashew nut, sesame, almond, and peanut discriminated between allergic and nonallergic children, to the respective nut or seed. The optimal allergen concentration and their optimal, positive, and negative cutoffs were identified for the BAT and the other tests, for each nut and seed. Using the BAT as a second step in the diagnostic process, after equivocal skin prick test and IgE to extracts and components, reduced the number of total OFCs by 5% to 15% and positive OFCs by 33% to 75% (except for hazelnut) with 0% false-negatives and a diagnostic accuracy of 96% to 100%.
Conclusion: The BAT proved to be a useful diagnostic tool, used in a stepwise approach, to predict the allergic status and reduce the number of OFCs in the Pronuts study participants with at least 1 nut allergy willing to consume selected nuts.
Impact of age on adherence and efficacy of peanut oral-immunotherapy using a standardized protocol.
Peanut oral immunotherapy (POIT) has been shown to be an effective therapy in peanut allergic children, as it improves food allergy-related quality of life [1-2] . Randomized controlled trials and observational, real world studies have shown that POIT may be effective and safe in children of all ages, although starting POIT at a younger age may be more efficacious and safer [3,5, 8] . Furthermore, initiation of POIT at a younger age may have higher rates of sustained unresponsiveness [3] . However, there has not been formal evaluation of this concept, using a standardized protocol [6] . The aim of our study was to examine associations between the age at initiation of POIT, and the safety of POIT, using a standardized protocol for all patients.
Reduced peanut sensitization with maternal peanut consumption and early peanut introduction while breastfeeding.
New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother-child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14-0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01-0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this "triple exposure" hypothesis.
IgE-binding to vicilin-like antimicrobial peptides is associated with systemic reactions to macadamia nut.
Background: Macadamia nut can induce fatal allergic reactions and changes in dietary habits will raise their consumption in industrialised countries. Until now diagnosis of macadamia nut allergy by sIgE solely relies on the macadamia nut extract, but single components are lacking. Methods: Macadamia nut proteins recognised by IgE from 2 macadamia nut extract positive sera were identified by mass spectrometry (vicilin-like antimicrobial peptides: VLAP). Sensitisation to macadamia nut extract and heterologously expressed isoform VLAP-2-3 was evaluated in 82 nut allergic (NA) and 27 tolerant (NT) patients (no tree nut allergy reported) comprehending 10 macadamia nut allergic (MA) and 18 explicitly reported macadamia nut tolerant patients (MT), using line blots. Co-sensitisation to additional VLAP isoforms and other vicilins was evaluated in 8 MA, 12 MT and 14 NA patients sensitised to VLAP-2-3. Functional properties were determined by indirect basophil activation. Results: Even though proteins recognised by IgE were identified as VLAP-2-1, 2-2 and 2-3, only peptides specifically belonging to VLAP-2-3 were detected by mass spectrometry. The macadamia nut extract was recognised by 33% of NA patients (27/82) including 3 MA patients and 26% of NT patients (7/27, 3 MT). Similarly, 29% of NA (24/82) patients showed partly strong sIgE-binding to VLAP-2-3 including 3 MA patients with systemic reactions to macadamia nut. Contrary, VLAP-2-3 was recognised by only 2 NT (1 MT) patients (7%) with very low sIgE titres. Simultaneous recognition of the isoforms VLAP-2-1 and 2-2 was observed in all patients positive for VLAP-2-3 with partly reduced sIgE titres in 59% of these patients. Additionally, all three VLAP isoforms were able to repeatedly induce BAT reactivity upon sensitisation with a MA serum.
Usefulness of r Ana o 3 assessment before oral food challenge to pistachio.
Cashew and pistachio both belong to the Anarcardiacae family. Cashew and pistachio allergies may cause severe symptoms such as anaphylaxis with a very low eliciting dose1,2 . The cashew 2S albumin r Ana o 3 is the only singleplex component-resolved diagnosis immunoassay currently available in clinical practice3-5 . Its structural similarity with the pistachio 2S albumin may explain the cross-reactivity between cashew and pistachio6 . The main objective of this study was to assess the performance of specific IgE to r Ana o 3 for the diagnosis of pistachio allergy.
Food and food products associated with food allergy and food intolerance-An overview.
Immune-mediated food allergy and non-immune mediated food intolerance are categorized as the most common adverse reactions resulting from the ingestion of certain foods. As there is no standard treatment, the possible remedy to avoid exposure to these adverse reactions is adhering to a strict diet that eliminates allergic and intolerant foods. The commonly consumed foods including dairy products, egg, fish, shellfish, tree nuts, peanut, soybean, and wheat-based products are proven to cause food allergy. Foods containing lactose, gluten, high FODMAPs, biogenic amines, and certain food additives leads to potential health risks in intolerant individuals. Besides, there are various foods whose mechanism of action in triggering food allergy and intolerance is yet to be defined. However, the public in-depth understanding of natural foods, processed foods, and packaged food products that induce allergic reactions and intolerance remains low. Therefore, awareness of diet that partially or completely excludes the intake of certain foods associated with these reactions should be widespread among the consumers.