Oral food challenge outcomes in a pediatric tertiary care center
BACKGROUND: Oral food challenges are the clinical standard for diagnosis of food allergy. Little data exist on predictors of oral challenge failure and reaction severity. METHODS: A retrospective chart review was done on all pediatric patients who had oral food challenges in a tertiary care pediatric allergy clinic from 2008 to 2010. RESULTS: 313 oral challenges were performed, of which the majority were to peanut (105), egg (71), milk (41) and tree nuts (29). There were 104 (33%) oral challenge failures. Children were more likely to fail an oral challenge if they were older (P = .04), had asthma (P = .001) or had atopic dermatitis (P = .03). Risk of challenge failure was significantly different between food allergens, with more failures noted for peanut than for tree nuts, milk or egg (P = .001). Among challenge failures, 19% met criteria for anaphylaxis. Significantly more tree nut and peanut challenges met criteria for anaphylaxis than milk or egg (P < .001). Skin test size and specific IgE level were significantly higher in those who failed oral challenges (P < .001). The highest rate of challenge failure and severity of failure was to cashew, with 63% of cashew challenges reacting, of which 80% met clinical criteria for anaphylaxis. CONCLUSION: The risk of challenge failure differed with type of food studied, with peanut and tree nut having a higher risk of challenge failure and anaphylaxis. Cashew in particular carried a high risk and caution must be exercised when performing these types of oral challenges in children.
Pistachio nut allergy: an updated overview.
Pistachio nut (Pistacia vera) is highly appreciated for its organoleptic characteristics and potential health benefits. However, this tree nut is also responsible for triggering moderate to severe IgE-mediated reactions in allergic individuals. Currently, pistachio nut allergy has gained some special attention, mainly due to its intrinsic relation with cashew nut allergy. Like for other nuts, the prevalence of pistachio nut allergy seems to be increasing at a global scale. Until now, there are five allergenic proteins officially listed for pistachio nut (Pis v 1, Pis v 2, Pis v 3, Pis v 4 and Pis v 5). Relevant data on their biochemical classification has become available, enabling establishing a correlation with the respective clinical symptoms. The establishment of an effective allergen risk assessment is a key issue for the food industry, policy makers and regulatory agencies. Thus, the availability of fast, specific and sensitive methods to detect trace amounts of allergens in processed foods is crucial. In the specific case of pistachio nut, there are some protein- and DNA-based methods for its detection/quantification in foods, which can aid to verify label information. Accordingly, all relevant research advances on this topic were summarised, updated and critically discussed in this review.
Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy
BACKGROUND. The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy. METHODS. We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test — one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age. RESULTS. Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy. CONCLUSIONS. The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.)
Sensitization profiles to peanut allergens across the United States.
BACKGROUND: Measurement of IgE antibody to peanut components can aid in the prediction of allergic responses the food. OBJECTIVE: To investigate the association between patient demographics (age, location) and allergic sensitization to peanut components across the United States. METHODS: Serum samples from 12,155 individuals with peanut extract specific IgE levels of 0.35 kUA/L or higher were analyzed for IgE antibodies to Ara h 1, 2, 3, 8, and 9 by ImmunoCAP. RESULTS: Among this population of peanut sensitized individuals, 79.1% of children (<3 years old) were sensitized to one or more peanut storage proteins (Ara h 1, 2, and/or 3), in contrast to 64.2% of adolescents (12-15 years old) and 22.1% of adults (>20 years old). Although sensitization was more prevalent to Ara h 2 than to the other storage proteins, a sizable fraction of patients were sensitized to Ara h 1 and/or 3 but not to Ara h 2 (eg, 13% of children <3 years old). Moreover, 9.6% of children, 10.2% of adolescents, and 10.5% of adults were sensitized to Ara h 9, whereas 2.4% of children, 49.4% of adolescents, and 42.9% of adults produced IgE to Ara h 8 (pathogenesis-related protein 10). Sensitization to Ara h 8 alone was markedly higher in the Northeastern United States relative to other regions of the country. CONCLUSION: We conclude that sensitization to individual peanut components is highly dependent on age and geographic location. Given that a severe allergic reaction to peanut is unlikely in individuals with isolated sensitization to Ara h 8, a sizable fraction of patients, in particular adolescents and adults, may be at lower risk than anticipated based only on demonstration of sensitization to whole peanut extract.
Immune mechanisms of food allergy and its prevention by early intervention.
The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants diet and conveyed more information regarding the evolution of IgE and IgG4 antibody responses to food antigens over time.
Reduced risk of peanut sensitization following exposure through breast-feeding and early peanut introduction.
BACKGROUND: Recent trials have shown that avoiding peanuts during infancy increases the risk of peanut allergy; however, these studies did not address maternal peanut consumption. OBJECTIVE: We sought to investigate the relationship between maternal peanut consumption while breast-feeding, timing of direct peanut introduction, and peanut sensitization at age 7 years. METHODS: Secondary analysis of a nested cohort within the 1995 Canadian Asthma Primary Prevention Study intervention study was performed. Breast-feeding and maternal and infant peanut consumption were captured by repeated questionnaires during infancy. Skin prick testing for peanut sensitization was performed at age 7 years. RESULTS: Overall, 58.2% of mothers consumed peanuts while breast-feeding and 22.5% directly introduced peanuts to their infant by 12 months. At 7 years, 9.4% of children were sensitized to peanuts. The lowest incidence (1.7%) was observed among children whose mothers consumed peanuts while breast-feeding and directly introduced peanuts before 12 months. Incidence was significantly higher (P < .05) if mothers consumed peanuts while breast-feeding but delayed introducing peanuts to their infant beyond 12 months (15.1%), or if mothers avoided peanuts themselves but directly introduced peanuts by 12 months (17.6%). Interaction analyses controlling for study group and maternal atopy confirmed that maternal peanut consumption while breast-feeding and infant peanut consumption by 12 months were protective in combination, whereas either exposure in isolation was associated with an increased risk of sensitization (P interaction = .003). CONCLUSIONS: In this secondary analysis, maternal peanut consumption while breast-feeding paired with direct introduction of peanuts in the first year of life was associated with the lowest risk of peanut sensitization, compared with all other combinations of maternal and infant peanut consumption.
Nut Allergy in Two Different Areas of Spain: Differences in Clinical and Molecular Pattern.
INTRODUCTION: Different clinical and molecular patterns of food allergy have been reported in different areas of the world. The aim of the study is to evaluate differences in allergen patterns among nut-allergic patients in two different areas of Spain. MATERIAL AND METHODS: A total of 77 patients with nut allergy from two different regions of Spain (Madrid and Asturias) were evaluated. RESULTS: Hazelnut, peanut, and walnut were the three most frequent nuts eliciting allergy in both regions, but in a different order. Patients from Madrid experienced systemic reactions more often than patients from Asturias (73.5% Madrid vs. 50.0%, p < 0.05). The percentage of sensitizations to LTP (Lipid Transfer Protein) was higher than Bet v 1 (p < 0.05) in the Madrid area. The percentage of sensitizations in Asturias area was similar to LTP than Bet v 1 (Pru p 3 46.4%, Bet v 1 42.9%, ns). Bet v 1 was the predominant allergen involved among hazelnut-allergic patients (56.2%), while LTP was more common in peanut-allergic patients (61.5%). CONCLUSION: Walnut, hazelnut, and peanut were the most frequent nuts eliciting allergy in Spain. Despite this, important differences in molecular pattern were appreciated not only between both regions, but also among nut-allergic patients in Asturias. The different molecular pattern was linked to the frequency of systemic symptoms.
Identification and characterization of the proteins bound by specific phage‐displayed recombinant antibodies (scFv) obtained against Brazil nut and almond extracts.
BACKGROUND: Almonds and Brazil nuts are widely consumed allergenic nuts whose presence must be declared according to food labelling regulations. Their detection in food products has been recently achieved by ELISA methods with recombinant antibodies (scFv) isolated against complete Brazil nut and almond protein extracts. The screening of phage-scFv libraries against complete protein extracts confers a series of advantages over the use of purified proteins, as recombinant proteins might alter their native folding. However, using this strategy, the nature of the target detected by phage-displayed antibodies remains unknown, and requires further research to identify whether they are nut allergens or other molecules present in the extract, but not related to their allergenic potential. RESULTS: Electrophoretic, chromatographic, immunological and spectrometric techniques revealed that the Brazil nut (BE95) and almond (PD1F6 and PD2C9) specific phage-scFvs detected conformational epitopes of the Brazil nut and almond 11S globulins, recognized by WHO/IUIS as Ber e 2 and Pru du 6 major allergens. Circular dichroism data indicated that severe heat treatment would entail loss of epitope structure, disabling scFv for target detection. CONCLUSIONS: The presence of important Brazil nut and almond allergens (Ber e 2 and Pru du 6) in foodstuffs can be determined by using phage-display antibodies BE95, PD1F6 and PD2C9 as affinity probes in ELISA.
BSACI guideline for the diagnosis and management of peanut and tree nut allergy.
Peanut nut and tree nut allergy are characterised by IgE mediated reactions to nut proteins. Nut allergy is a global disease. Limited epidemiological data suggest varying prevalence in different geographical areas. Primary nut allergy affects over 2% of children and 0.5% of adults in the UK. Infants with severe eczema and/or egg allergy have a higher risk of peanut allergy. Primary nut allergy presents most commonly in the first five years of life, often after the first known ingestion with typical rapid onset IgE-mediated symptoms. The clinical diagnosis of primary nut allergy can be made by the combination of a typical clinical presentation and evidence of nut specifc IgE shown by a positive skin prick test (SPT) or specific IgE (sIgE) test. Pollen food syndrome is a distinct disorder, usually mild, with oral/pharyngeal symptoms, in the context of hay fever or pollen sensitisation, which can be triggered by nuts. It can usually be distinguish clinically from primary nut allergy. The magnitude of a SPT or sIgE relates to the probability of clinical allergy, but does not relate to clinical severity. SPT of ≥ 8 mm or sIgE ≥ 15 KU/L to peanut is highly predictive of clinical allergy. Cut off values are not available for tree nuts. Test results must be interpreted in the context of the clinical history. Diagnostic food challenges are usually not necessary but may be used to confirm or refute a conflicting history and test result. As nut allergy is likely to be a long-lived disease, nut avoidance advice is the cornerstone of management. Patients should be provided with a comprehensive management plan including avoidance advice, patient specific emergency medication and an emergency treatment plan and training in administration of emergency medication. Regular re-training is required.
Cross-reactivity profiles of legumes and tree nuts using the xMAP® multiplex food allergen detection assay.
The homology between proteins in legumes and tree nuts makes it common for individuals with food allergies to be allergic to multiple legumes and tree nuts. This propensity for allergenic and antigenic cross-reactivity means that commonly employed commercial immunodiagnostic assays (e.g., dipsticks) for the detection of food allergens may not always accurately detect, identify, and quantitate legumes and tree nuts unless additional orthogonal analytical methods or secondary measures of analysis are employed. The xMAP® Multiplex Food Allergen Detection Assay (FADA) was used to determine the cross-reactivity patterns and the utility of multi-antibody antigenic profiling to distinguish between legumes and tree nuts. Pure legumes and tree nuts extracted using buffered detergent displayed a high level of cross-reactivity that decreased upon dilution or by using a buffer (UD buffer) designed to increase the stringency of binding conditions and reduce the occurrence of false positives due to plant-derived lectins. Testing for unexpected food allergens or the screening for multiple food allergens often involves not knowing the identity of the allergen present, its concentration, or the degree of modification during processing. As such, the analytical response measured may represent multiple antigens of varying antigenicity (cross-reactivity). This problem of multiple potential analytes is usually unresolved and the focus becomes the primary analyte, the antigen the antibody was raised against, or quantitative interpretation of the content of the analytical sample problematic. The alternative solution offered here to this problem is the use of an antigenic profile as generated by the xMAP FADA using multiple antibodies (bead sets). By comparing the antigenic profile to standards, the allergen may be identified along with an estimate of the concentration present. Cluster analysis of the xMAP FADA data was also performed and agreed with the known phylogeny of the legumes and tree nuts being analyzed. Graphical abstract The use of cluster analysis to compare the multi-antigen profiles of food allergens.