Natural Variation of Hazelnut Allergenicity: Is There Any Potential for Selecting Hypoallergenic Varieties?

Hazelnuts (Corylus avellana L.) have an important role in human nutrition and health. However, they are a common cause of food allergy. Due to hazelnut varietal diversity, variety-dependent differences in the IgE-binding properties may be suspected, which could allow therapeutic strategies based on the use of hypoallergenic varieties to induce desensitization. In a proteogenomic approach, we aimed to evaluate the allergenic potential of a genetically diverse set of hazelnuts (n = 13 varieties). Minor differences were found at the level of genes encoding important allergens, namely Cor a 8, Cor a 9, and Cor a 14. Nevertheless, IgE-reactivity was similar for all varieties using sera from seven allergic individuals. The predominant IgE-reactive proteins were Cor a 9 (100%) and Cor a 1.04 (60%), with the former being the most frequently identified by a two-dimensional gel electrophoresis (2-DE)-based proteomic approach. Therefore, it seems that the conventional exclusion diet will hold its ground for the time being.

Real-world tree nut consumption in peanut-allergic individuals.

BACKGROUND: Individuals with peanut allergy often avoid tree nuts, yet true rates of tree nut allergy in peanut-allergic individuals are as low as 7%. OBJECTIVE: To examine tree nut sensitization patterns in peanut-allergic individuals, patient and family choice regarding tree nut consumption, and factors that influence consumption of tree nuts. METHODS: All patients presenting for peanut allergy evaluation to an outpatient allergy office were included during a 4-month period. In addition to demographic information, sensitization to tree nuts and tree nut consumption were collected. Logistic regression was performed to generate odds ratios with 95% CIs in univariate and multivariate analyses for variables that predict tree nut consumption. RESULTS: A total of 258 individuals with peanut allergy were enrolled. Ninety-five (36.8%) consumed all tree nuts ad libitum, 63 (24.4%) consumed some but not all tree nuts, and 100 (38.8%) consumed no tree nuts. Of the 100 electively avoiding all tree nuts, the most commonly reported reason was fear of cross-contact (50%). Although there was no difference between rates of sensitization between individual tree nuts (P = .056), cashew and pistachio had higher serum specific IgE levels compared with other tree nuts (P < .001). The tree nut most commonly consumed by peanut-allergic individuals was almond (P < .001). Consumption of foods with precautionary labeling was the strongest predictor of tree nut consumption in peanut allergic individuals (P < .001) CONCLUSION: Our data highlight the potential for safe introduction of tree nuts in peanut-allergic individuals and indicate that peanut-allergic individuals who consume foods with precautionary labeling are most likely to consume tree nuts.

A protocol for a systematic review to identify allergenic tree nuts and the molecules responsible for their allergenic properties.

Food regulations require that tree nuts and derived ingredients are included on food labels in order to help individuals with IgE-mediated allergies to avoid them. However, there is no consensus regarding which tree nut species should be included in this definition and specified on food labels. Allergen detection methods used for monitoring foods target allergen molecules, but it not clear which are the most relevant molecules to choose. A modified population-exposure-comparators-outcome (PECO) approach has been developed to systematically review the evidence regarding (1) which allergenic tree nuts should be included in food allergen labelling lists and (2) which are the clinically relevant allergens which should be used as analytical targets. A search strategy and criteria against which the evidence will be evaluated have been developed. The resulting evidence will be used to rank tree nuts with regards their ability to cause IgE-mediated allergies, and allergen molecules regarding their capacity to elicit an allergic reaction. The results of the systematic review will enable risk assessors and managers to identify tree nut species that should be included in food allergen labelling lists and ensure analytical methods for determination of allergens in foods are targeting appropriate molecules.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut allergy across Europe. METHODS: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

The ability of adults and children to visually identify peanuts and tree nuts.

BACKGROUND: Peanuts and tree nuts are common food allergens and are the leading cause of fatalities from food-induced anaphylaxis. Dietary avoidance is the primary management of these allergies and requires the ability to identify peanuts or tree nuts. OBJECTIVES: To investigate the ability of adults and children to visually identify peanuts and tree nuts. METHODS: A nut display was assembled that held peanuts and 9 tree nuts in a total of 19 different forms. Persons 6 years or older completed a worksheet to name the items. RESULTS: One-thousand one-hundred five subjects completed the study. The mean number of peanuts and tree nuts identified by all subjects was 8.4 (44.2%) out of a possible 19. The mean for children ages 6 to 18 was 4.6 (24.2%), compared with 11.1 (58.4%) for adults older than 18 (P < .001). The most commonly identified items were peanut in the shell and without the shell. The least identified was hazelnut (filbert) in the shell and without the shell. No difference was seen in the performance of peanut- or tree nut-allergic subjects compared with nonallergic subjects. Fifty percent of subjects with a peanut or tree nut allergy correctly identified all forms of peanuts or tree nuts to which they are allergic. Parents of peanut- or tree nut-allergic children did no better than parents of children without such allergy. CONCLUSIONS: Overall, both children and adults are unreliable at visually identifying most nuts. Treatment of nut allergies with dietary avoidance should include education for both adults and children on identification of peanuts and tree nuts.

Age-related sensitization profiles for hazelnut (Corylus avellana) in a birch-endemic region.

BACKGROUND: Symptoms of hazelnut allergy seem related to geographic and possibly age variations in allergen recognition. OBJECTIVE: To investigate sensitization profiles of hazelnut allergy in different age groups in a birch-endemic region using component resolved diagnosis (CRD) by microarray. METHODS: Sixty-five patients with hazelnut allergy, 27 healthy control individuals tolerant to hazelnut, and 34 birch pollen allergic but hazelnut tolerant individuals were included. All blood samples were analyzed using ISAC microarray. RESULTS: Twenty-nine patients with hazelnut allergy suffered from a systemic reaction (17 preschool children with a median age of 2 years, six school children, and six adults), whereas 36 patients reported an oral allergy syndrome (OAS; three preschool and nine school children and 24 adults). In the hazelnut allergic preschool children with systemic reactions, 65% were sensitized to Cor a 9, 12% to Cor a 8, 18% to Cor a 1.04, 6% to Cor a 1.0101, and 29% to Bet v 1. Of the school-aged systemic reactors, 50% were sensitized to Cor a 9, 17% to Cor a 8, 50% to Cor a 1.04 and Cor a 1.0101, and 67% to Bet v 1. In adults with hazelnut allergy, 3.3% were sensitized to Cor a 9, 6.7% to Cor a 8, 90% to Cor a 1.04 and Bet v 1, and 87% to Cor a 1.0101. In regard to systemic reactors in this group, 17% were sensitized to Cor a 9, 33% to Cor a 8 and Cor a 1.0101, and 50% to Cor a 1.04 and Bet v 1. In the patients with OAS, irrespective the age group, all were sensitized to Bet v 1 and over 97% to Cor a 1.04 and Cor a 1.0101. No sensitization to Cor a 9 or Cor a 8 was found in patients with only an OAS. Of the patients with birch pollen allergy, tolerant to hazelnut, none were sensitized to Cor a 9 or Cor a 8, 56% to Cor a 1.0101, 82% to Cor a 1.04, and 92% to Bet v 1. In healthy controls, no sensitization to components of hazelnut, hazel pollen or birch pollen was demonstrable. CONCLUSION: Hazelnut allergy in a birch-endemic region exhibits age-related sensitization profiles with distinct clinical outcomes that can be identified using CRD. The majority of hazelnut allergic preschool and school children in a birch-endemic region show systemic reactions on consumption of processed hazelnut, mostly being sensitized to the hazelnut legumin-like allergen Cor a 9 but unrelated to birch pollen allergy. In contrast, adults generally suffer from an OAS apparently as a result of cross-reactivity between Cor a 1.04 from hazelnut and Bet v 1 from birch pollen.

Clinical allergy to hazelnut and peanut: identification of T cell cross-reactive allergens.

BACKGROUND: Peanut and tree nut allergies are life-threatening conditions for many affected individuals worldwide. Currently there is no cure. While co-allergy to peanut and tree nuts is a common clinical observation, and IgE cross-reactivity between peanut and tree nuts is reported, T cell cross-reactivity is poorly defined. METHODS: Hazelnut-specific T cell lines were established using peripheral blood mononuclear cells from 5 subjects with co-allergy to hazelnut and peanut. These lines were stimulated with hazelnut and peanut extracts and purified major peanut allergens, Ara h 1 and Ara h 2. Proliferation was determined by (3)H-thymidine incorporation and secretion of key Th1 (IFN-γ) and Th2 (IL-5) cytokines analysed by ELISA. RESULTS: Hazelnut-specific T cell lines from all 5 subjects proliferated upon stimulation with both hazelnut and peanut extracts and for 4 subjects, to Ara h 1 and/or Ara h 2. Proliferating cells were mainly CD4+ T cells and produced both IL-5 and IFN-γ in response to hazelnut and peanut stimulation. Mitogenicity of extracts and allergens was excluded by their lack of stimulation of house dust mite-specific T cells. CONCLUSION: Our finding that hazelnut and peanut co-allergy is associated with cross-reactive T cell responses, driven partly by cross-reactivity to the major peanut allergens Ara h 1 and Ara h 2, points to future development of allergen immunotherapy by targeting cross-reactive T cells.

Macadamia nut allergy: 2 case reports and a review of the literature.

We report on 2 patients with anaphylaxis rom Macadamia nut. Temporal relationship between consumption of the nut strongly suggested the diagnosis. Clinical suspicion was supported by the presence of positive specific IgE and/or the positive skin test and/or and the basophil activation test.