Roux, K.H., S.S. Teuber, S.K. Sathe, 2003. Tree nut allergens. Int Arch Allergy Immunol. 131:234–244.
Allergic reactions to tree nuts can be serious and life threatening. Considerable research has been conducted in recent years in an attempt to characterize those allergens that are most responsible for allergy sensitization and triggering. Both native and recombinant nut allergens have been identified and characterized and, for some, the IgE-reactive epitopes described. Some allergens, such as lipid transfer proteins, profilins, and members of the Bet v 1-related family, represent minor constituents in tree nuts. These allergens are frequently cross-reactive with other food and pollen homologues, and are considered panallergens. Others, such as legumins, vicilins, and 2S albumins, represent major seed storage protein constituents of the nuts. The allergenic tree nuts discussed in this review include those most commonly responsible for allergic reactions such as hazelnut, walnut, cashew, and almond as well as those less frequently associated with allergies including pecan, chestnut, Brazil nut, pine nut, macadamia nut, pistachio, coconut, Nangai nut, and acorn.
Teuber, S.S., S.S. Comstock, S.K. Sathe, K.H. Roux, 2003. Tree nut allergy. Current Allergy and Asthma Reports. 3:54–61.
Tree nuts are clinically associated with severe immunoglobulin E–mediated systemic allergic reactions independent of pollen allergy and with reactions that are usually confined to the oral mucosa in patients with immunoglobulin E directed toward cross-reacting pollen allergens. The latter reactions can progress to severe and life-threatening episodes in some patients. Many patients with severe tree nut allergy are co-sensitized to peanut. Clinical studies on cross-reactivity between the tree nuts are few in number, but based on reports to date, avoidance of the other tree nuts once sensitivity is diagnosed appears prudent unless specific challenges are performed to ensure clinical tolerance. Even then, great care must be taken to avoid cross-contamination. As with other severe food allergies, a recurrent problem in clinical management is the failure of physicians to prescribe self-injectable epinephrine to patients who are at risk of anaphylaxis.
Akkerdaas, J.H., M. Wensing, A.C. Knulst, M. Krebitz, H. Breiteneder, S. de Vries, A.H. Penninks, R.C. Aalberse, S.L. Hefle, R. van Ree, 2003. How accurate and safe is the diagnosis of hazelnut allergy by means of commercial skin prick test reagents? Int Arch Allergy Immunol. 132:132–140.
Background: Allergy to tree nuts, like hazelnuts, ranks among the most frequently observed food allergies. These allergies can start at early childhood and are, in contrast to other food allergies, not always outgrown by the patient. Tree nut allergy is frequently associated with severe reactions. Diagnosis partially relies on in vivo testing by means of a skin prick test (SPT) using commercially available SPT reagents. Methods: Protein and allergen composition of nine commercial SPT solutions was evaluated using standard protein detection methods and specific immunoassays for measurement of five individual allergens. Diagnostic performance was assessed by SPT in 30 hazelnut-allergic subjects, of which 15 were provocation proven. Results: Protein concentrations ranged from 0.2–14 mg/ml. SDS-PAGE/silver staining revealed clear differences in protein composition. The major allergen Cor a 1 was present in all extracts but concentrations differed up to a factor 50. An allergen associated with severe symptoms, Cor a 8 (lipid transfer protein), was not detected on immunoblot in three products, and concentrations varied by more than a factor 100 as was shown by RAST inhibition. Similar observations were made for profilin, thaumatin-like protein and a not fully characterized 38-kD allergen. Ratios of individual allergens were variable among the nine extracts. SPT showed significant difference, and 6/30 patients displayed false-negative results using 3/9 products. Conclusion: Variability in the composition of products for the diagnosis of hazelnut allergy is extreme. Sometimes, allergens implicated in severe anaphylaxis are not detected by immunoblotting. These shortcomings in standardisation and quality control can potentially cause a false-negative diagnosis in subjects at risk of severe reactions to hazelnuts.
Ibáñez, M.D., M. Lombardero, M.M San Ireneo, M.C. Muñoz, 2003. Anaphylaxis induced by pine nuts in two young girls. Pediatr Allergy Immunol. 14:317–319.
Pine nuts are the seeds of Pinus pinea. There are few reported cases of allergy to pine nut.W e describe two young girls with anaphylaxis caused by small amounts of pine nuts.Spe cific IgE to pine nut was demonstrated by skin prick tests and RAST but no IgE to other nuts and pine pollen was detected.The patients had IgE against a pine nut protein band with apparent molecular weights of ~17 kDa that could be considered as the main allergen. Our patients were monosensitized to pine nut and the 17-kDa protein could be correlated with the severe clinical symptoms.
Hansen, K.S., B.K. Ballmer-Weber, D. Lüttkopf, P.S. Skov, B. Wüthrich, C. Bindslev-Jensen, S. Vieths, L.K. Poulsen, 2003. Roasted hazelnuts – allergenic activity evaluated by double-blind, placebo-controlled food challenge. Allergy. 58:132–138.
Background: Allergy to hazelnuts is a common example of birch pollen related food allergy. Symptoms upon ingestion are often confined to the mouth and throat, but severe systemic reactions have been described in some patients. The aim of the study was to evaluate the reduction in allergenicity by roasting of the nuts. Methods: Double-blind, placebo-controlled food challenges (DBPCFC) with roasted hazelnuts (140°C, 40 min) were performed in 17 birch pollen allergic patients with DBPCFC-confirmed food allergy to raw hazelnuts. The effect of roasting was further evaluated by skin prick test (SPT), histamine release (HR), measurement of specific IgE, and IgE-inhibition experiments. Results: In 5/17 patients the DBPCFC with the roasted nuts were positive. The symptoms were generally mild and included OAS (oral allergy syndrome) in all patients. Roasting of the nuts significantly reduced the allergenic activity evaluated by SPT, HR, specific IgE, and IgE-inhibition. Immunoblotting experiments with recombinant hazelnut allergens showed sensitization against Cor a 1.04 in 16/17 patients and against Cor a 2 in 7/17 patients. None of the patients were sensitized to Cor a 8. Challenge-positive patients did not differ from the rest in IgE-binding pattern. Conclusions: All the applied methods indicated that roasting of hazelnuts reduces the allergenicity, but since 5/17 birch pollen allergic patients were DBPCFC-positive to the roasted nuts, ingestion of roasted hazelnuts or products containing roasted hazelnuts can not be considered safe for a number of hazelnut allergic consumers. For patients with a history of severe allergic symptoms upon ingestion of hazelnuts, thorough and conscientious food labelling of hazelnuts and hazelnut residues is essential.
de Leon, M.P., I.N. Glaspole, A C. Drew, J.M. Rolland, R.E. O’Hehir, C. Suphioglu, 2003. Immunological analysis of allergenic cross-reactivity between peanut and tree nuts. Clin Exp Allergy. 33:1273–1280.
Background: Peanut and tree nut allergy is characterized by a high frequency of life-threatening anaphylactic reactions and typically lifelong persistence. Peanut allergy is more common than tree nut allergy, but many subjects develop hypersensitivity to both peanuts and tree nuts. Whether this is due to the presence of cross-reactive allergens remains unknown. Objective: The aim of this study was to investigate the presence of allergenic cross-reactivity between peanut and tree nuts. Methods Western blotting and ELISA were performed using sera from subjects with or without peanut and tree nut allergy to assess immunoglobulin E (IgE) reactivity to peanut and tree nut extracts. Inhibition ELISA studies were conducted to assess the presence of allergenic cross-reactivity between peanut and tree nuts. Results: Western blot and ELISA results showed IgE reactivity to peanut, almond, Brazil nut, hazelnut and cashew nut for peanut- and tree nut-allergic subject sera. Raw and roasted peanut and tree nut extracts showed similar IgE reactivities. Inhibition ELISA showed that pre-incubation of sera with almond, Brazil nut or hazelnut extracts resulted in a decrease in IgE binding to peanut extract, indicating allergenic cross-reactivity. Pre-incubation of sera with cashew nut extract did not cause any inhibition. Conclusion: These results show that multiple peanut and tree nut sensitivities observed in allergic subjects may be due to cross-reactive B cell epitopes present in different peanut and tree nut allergens. The plant taxonomic classification of peanut and tree nuts does not appear to predict allergenic cross-reactivity.
Rancé, F., E. Bidat, T. Bourrier, D. Sabouraud, 2003. Cashew allergy: observations of 42 children without associated peanut allergy. Allergy. 58:1311–1314.
Background: Cashew allergy seems to be increasingly frequent. The goal of the present study was to analyse the clinical features and results of investigations of 42 children with cashew allergy. Methods: The clinical features and results of skin prick tests, specific IgE assays, and food challenges were analysed. Results: The mean age at first allergic reaction was 2 years and the mean age at diagnosis of cashew allergy was 2.7 years. One in five children (12%) had a prior history of exposure to cashew nuts. Fifty-six per cent had skin symptoms, 25% had respiratory signs and 17% had digestive signs. Eighteen children had proven, associated food allergies (pistachio, seven; egg, five; mustard, three; shrimp, two; cow milk, one). The mean wheal diameter of the skin prick tests was 7 mm (3–16 mm) and the mean specific IgE level was 3.1 kUA/L (<0.35–>100 kUA/L). Eight children had positive food challenges. Conclusion: The increase in cashew allergy is worrying because it affects young children who may have a reaction without ever having been exposed to cashews. Almost one-third of children are allergic to pistachios, which belong to the same botanical family as cashews. Clinical history is generally and sufficiently suggestive to diagnose cashew allergy without recourse to food challenges.
Clark A.T., P.W. Ewan, 2003. Interpretation of tests for nut allergy in one thousand patients, in relation to allergy or tolerance. Clin Exp Allergy. 33(8):1041-1045.
BACKGROUND: Peanut and tree nut allergy are common, increasing in prevalence and the commonest food cause of anaphylaxis. In the USA, 7.8% are sensitized (have nut-specific IgE), but not all those sensitized are allergic. Lack of data makes interpretation of tests for nut-specific IgE difficult. OBJECTIVES: This is the first study to investigate the clinical significance of test results for peanut and tree nut allergy in allergic or tolerant patients. Findings are related to the severity of the allergy. METHOD: An observational study of 1000 children and adults allergic to at least one nut. History of reactions (severity graded) or tolerance to up to five nuts was obtained and skin prick test (SPT)/serum-specific IgE (CAP) performed. RESULTS: There was no correlation between SPT size and graded severity of worst reaction for all nuts combined or for peanut, hazelnut, almond and walnut. For CAP, there was no correlation for all nuts. Where patients tolerated a nut, 43% had positive SPT of 3-7 mm and 3% ≥ 8 mm. For CAP, 35% were positive (0.35-14.99 kU/L) and 5% ≥ 15 kU/L. In SPT range 3-7 mm, 54% were allergic and 46% were tolerant. There was poor concordance between SPT and CAP (66%). Of patients with a clear nut-allergic history, only 0.5% had negative SPT, but 22% negative CAP. CONCLUSIONS: Magnitude of SPT or CAP does not predict clinical severity, with no difference between minor urticaria and anaphylaxis. SPT is more reliable than CAP in confirming allergy. Forty-six per cent of those tolerant to a nut have positive tests > or = 3 mm (sensitized but not allergic). One cannot predict clinical reactivity from results in a wide ‘grey area’ of SPT 3-7 mm; 22% of negative CAPs are falsely reassuring and 40% of positive CAPs are misleading. This emphasizes the importance of the history. Understanding this is essential for accurate diagnosis. Patients with SPT > or = 8 mm and CAP ≥ 15 kU/L were rarely tolerant so these levels are almost always (in ≥ 95%) diagnostic.
Wang, F., J.M. Robotham, S.S. Teuber, S.K. Sathe, K.H. Roux, 2003. Ana o 2, a major cashew (Anacardium occidentale L.) nut allergen of the legumin family. Int Arch Allergy Immunol. 132:27–39.
Background: We recently cloned and described a vicilin and showed it to be a major cashew allergen. Additional IgE-reactive cashew peptides of the legumin group and 2S albumin families have also been reported. Here, we attempt to clone, express and characterize a second major cashew allergen. Methods: A cashew cDNA library was screened with human IgE and rabbit IgG anticashew extract antisera, and a reactive nonvicilin clone was sequenced and expressed as a fusion protein in Escherichia coli. Immunoblotting was used to screen for reactivity with patients’ sera, and inhibition of immunoblotting was used to identify the corresponding native peptides in cashew nut extract. The identified allergen was subjected to linear epitope mapping using SPOTs solid-phase synthetic peptide technology. Results: Sequence analysis showed the selected clone, designated Ana o 2, to encode for a member of the legumin family (an 11S globulin) of seed storage proteins. By IgE immunoblotting, 13 of 21 sera (62%) from cashew-allergic patients were reactive. Immunoblot inhibition data showed that the native Ana o 2 constitutes a major band at approximately 33 kD and a minor band at approximately 53 kD. Probing of overlapping synthetic peptides with pooled human cashew-allergic sera identified 22 reactive peptides, 7 of which gave strong signals. Several Ana o 2 epitopes were shown to overlap those of the peanut legumin group allergen, Ara h 3, in position but with little sequence similarity. Greater positional overlap and identity was observed between Ana o 2 and soybean glycinin epitopes. Conclusions: We conclude that this legumin-like protein is a major allergen in cashew nut.
Akkerdaas, J.H., M. Wensing, A.C. Knulst, M. Krebitz, H. Breiteneder, S. de Vries, A.H. Penninks, R.C. Aalberse, S.L. Hefle, R. van Ree, 2003. How accurate and safe is the diagnosis of hazelnut allergy by means of commercial skin prick test reagents? Int Arch Allergy Immunol. 132:132–140.
Background: Allergy to tree nuts, like hazelnuts, ranks among the most frequently observed food allergies. These allergies can start at early childhood and are, in contrast to other food allergies, not always outgrown by the patient. Tree nut allergy is frequently associated with severe reactions. Diagnosis partially relies on in vivo testing by means of a skin prick test (SPT) using commercially available SPT reagents. Methods: Protein and allergen composition of nine commercial SPT solutions was evaluated using standard protein detection methods and specific immunoassays for measurement of five individual allergens. Diagnostic performance was assessed by SPT in 30 hazelnut-allergic subjects, of which 15 were provocation proven. Results: Protein concentrations ranged from 0.2–14 mg/ml. SDS-PAGE/silver staining revealed clear differences in protein composition. The major allergen Cor a 1 was present in all extracts but concentrations differed up to a factor 50. An allergen associated with severe symptoms, Cor a 8 (lipid transfer protein), was not detected on immunoblot in three products, and concentrations varied by more than a factor 100 as was shown by RAST inhibition. Similar observations were made for profilin, thaumatin-like protein and a not fully characterized 38-kD allergen. Ratios of individual allergens were variable among the nine extracts. SPT showed significant difference, and 6/30 patients displayed false-negative results using 3/9 products. Conclusion: Variability in the composition of products for the diagnosis of hazelnut allergy is extreme. Sometimes, allergens implicated in severe anaphylaxis are not detected by immunoblotting. These shortcomings in standardization and quality control can potentially cause a false-negative diagnosis in subjects at risk of severe reactions to hazelnuts.
