Gastrointestinal digestion of hazelnut allergens on molecular level: Elucidation of degradation kinetics and resistant immunoactive peptides using mass spectrometry.
SCOPE: Allergy to hazelnut seeds ranks among the most prevalent food allergies in Europe. The aim of this study was to elucidate the gastrointestinal digestion of hazelnut allergens on molecular level. METHODS AND RESULTS: Hazelnut flour was digested in vitro following the Infogest consensus model. For six allergenic proteins, the time-dependent course of digestion was monitored by SDS-PAGE and HPLC-MS/MS, and degradation products were characterized by a bottom-up proteomics approach. Depending on the molecular structure, a specific biochemical fate was observed for each allergen, and degradation kinetics were traced back to the peptide level. 1183 peptides were characterized, including 130 peptides that carry known IgE-binding epitopes and may represent sensitizers for hazelnut allergy. The kinetics of peptide formation and degradation were determined by label free quantification and follow a complex multi-stage mechanism. CONCLUSION: We present a comprehensive survey on the gastrointestinal digestion of a relevant allergenic food on level of the peptidome, including the first systematic characterization and quantification of degradation products. This provides information on the differential resistance of plant food allergens and their structural elements undergoing digestion and forms the basis for a deeper understanding of the molecular principles responsible for sensitization to food allergy.
Prediction of cashew nut allergy in sensitised children.
As an alternative to the costly, time-consuming and possibly stressful double-blind, placebo-controlled challenge (DBPCFC) test, a model to predict the risk of cashew nut allergy was studied incorporating patient characteristics, standard diagnostic parameters (specific IgE (sIgE) and Skin Prick Test (SPT)) as well as component resolved diagnosis (CRD).
Characteristics of tree nut challenges in tree nut allergic and tree nut sensitized individuals.
BACKGROUND: Characteristics and outcomes of tree nut (TN) oral food challenges (OFCs) in patients with TN allergy or sensitization alone are poorly studied. OBJECTIVE: To determine the relation between TN sensitization levels and OFC outcomes. METHODS: Open TN OFCs performed from 2007 through 2015 at a referral center were analyzed to compare outcome based on skin prick test (SPT) wheal size, food-specific immunoglobulin E (sIgE), peanut co-allergy, and TN sensitization only vs TN allergy with sensitization to other TNs. Delayed OFC was defined as longer than 12 months from the time of an sIgE level lower than 2 kUA/L. RESULTS: Overall passage rate was 86% for 156 TN OFCs in 109 patients (54 almond, 28 cashew, 27 walnut, 18 hazelnut, 14 pecan, 13 pistachio, and 2 Brazil nut). Passage rates were 76% (n = 67) in patients with a history of TN allergy who were challenged to another TN to which they were sensitized and 91% (n = 65) in those with TN sensitization only (mean sIgE 1.53 kUA/L; range 0.35-9.14). Passage rates were 89% (n = 110 of 124) for a TN sIgE level lower than 2 kUA/L and 69% (11 of 16) for a TN sIgE level of at least 2 kUA/L. In 44 challenges in patients with peanut allergy and TN co-sensitization, the TN OFC passage rate was 96%. In 41 TN OFCs with a TN SPT wheal size of at least 3 mm, 61% passed, with a mean wheal size of 4.8 mm (range 3-11) in those passing vs 9 mm (range 3-20) in those failing. CONCLUSION: TN challenges are frequently passed in patients with TN sensitization with or without a history of TN reactivity despite a TN SPT wheal of at least 3 mm or a TN sIgE level of at least 2 kUA/L. Nearly all patients with peanut allergy and TN co-sensitization passed the TN challenge, questioning the clinical relevance of "co-allergy."
Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children.
BACKGROUND: Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically. OBJECTIVE: We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs). METHODS: Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat. RESULTS: Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies. CONCLUSIONS: Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.
Peanut oleosins associated with severe peanut allergy-Importance of lipophilic allergens for comprehensive allergy diagnostics.
BACKGROUND: Peanut allergy is one of the most common and most severe food allergies in Western countries and its accurate diagnosis to prevent potential life-threatening allergic reactions is crucial. However, aqueous extracts used for routine diagnostic measurements are devoid of lipophilic allergens such as oleosins. We have recently succeeded in the isolation and purification of these unique proteins, and the current study evaluates their allergenic potential and clinical relevance. OBJECTIVE: We sought to assess allergenicity and sensitization prevalence of oleosins obtained from both raw and in-shell roasted peanuts. Additionally, we tested the utilization of natural and recombinant oleosins for allergy diagnostic purposes. METHODS: Oleosin sensitization, prevalence, and impact of thermal processing were analyzed by immunoblot with sera from 52 peanut-allergic individuals displaying different clinical phenotypes. The application of natural and recombinant oleosins for allergy diagnostics was investigated by basophil activation test (BAT). IgE-binding epitopes were identified by oligopeptide microarray. RESULTS: Sensitization to oleosins was observed exclusively in peanut-allergic subjects suffering from severe systemic reactions. IgE-binding capacity of oleosins derived from in-shell roasted peanuts was increased as shown by immunoblot analysis and BAT. Both natural and recombinant molecules can be used to identify oleosin-sensitized patients by BAT. A linear epitope of Ara h 15 was determined which displays high similarity to other seed-derived oleosins. CONCLUSION: Oleosins are clinically relevant peanut allergens and most likely associated with severe allergic symptoms. In-shell roasting increases their allergenicity, which is consistent with the observation that most allergic reactions are in connection with roasted peanuts.
Update on Timing and Source of ‘Allergenic' Foods.
As the prevalence of food allergies in many communities continues to rise, the question of when in infancy to introduce any solid foods, or specific 'more allergenic' foods, as a food allergy prevention strategy has been debated. Observational studies have found that introducing any solid foods prior to 4 months of age was associated with an increased risk of allergic disease. Hence, the current allergy prevention consensus recommendation is that the introduction of any solid foods should commence after 4 months of age. Over recent years, several randomized controlled trials have been conducted to investigate the 'ideal' timing of introduction of some specific 'more allergenic' foods (including peanuts and eggs) into infant diets. To date, the results from three of these trials have determined that there is no reason to delay the introduction of the 'more allergenic' foods into the infant's diet after solid foods have commenced. However, these trials have also highlighted the finding that some infants are sensitized to food allergens before any known ingestion of solid foods. Thus, future research needs to focus on strategies to prevent early-life food allergen sensitization prior to complementary feeding.
The role of dietary interventions in the prevention of IgE‐mediated food allergy in children.
Over the last 30 years, the prevalence of food allergy has been on the rise and remains a disease that can have a significant impact on the quality of life of children and their families. There are several hypotheses that have been suggested to account for the increasing prevalence, but this review will focus on the impact that dietary factors have on food allergy development. In the past food allergy, prevalence has largely focused on allergen avoidance; however, there is increasing evidence from interventional studies that have shown that early introduction to potential food allergens may have a beneficial role in allergy prevention. This review aims to look at the evidence in support of early introduction of allergens into infant diets to prevent against the development of food allergy.
Phenotypical characterization of peanut allergic children with differences in cross‐allergy to tree nuts and other legumes.
BACKGROUND: Peanut allergy in children is often associated with allergies to tree nuts and/or legumes. The aim of the present study was to analyze in cluster a cohort of children allergic to peanuts and assessed for cross-reactivity to nuts and legumes and to identify different phenotypes. METHODS: We included retrospectively 317 children with peanut allergy evaluated at the Allergy Unit of the Saint Vincent Hospital of Lille in the last 12 years. A complete work-up for peanut allergy and nuts and legumes was carried out for each patient. A hierarchical agglomerative clustering method was used to search for clusters of individuals in the evaluated cohort. RESULTS: Cross-allergy to TN and/or other legumes was identified in 137 patients (43.2%), atopic dermatitis being a major risk factor (adjusted OR = 16 [95%CI: 7.4-37]; p<0.001). Three phenotypes emerged from cluster analysis. Cluster 1 (72 patients) is characterized by high level of rAra h 2, low threshold reactive doses for peanut and high proportion of asthma; Cluster 2 (93 patients) is characterized by high threshold reactive doses for peanut and the lowest proportion of cross-allergy to TN and/or legumes; Cluster 3 (152 patients) has a high risk of cross-allergy to TN and/or legumes and most patients suffer from eczema. CONCLUSIONS: The three phenotypes highlighted by the present study could be useful to identify children with high risk of cross-allergic reaction to TNs and legumes early after PA diagnosis.
Can pan-allergens affect the sensitization pattern?
The present study tested the hypothesis that a pan-allergen sensitization may affect the sensitization pattern. For this reason, 22 sensitization pattern allergens (SPA), common in Genoa (Italy), were selected for analyses. Successively, five of them, such as Pru p 3 as representative for LTP family, Bet v 1 and Pru p 1 for PR-10, and Bet v 2 and Pru p 4 for Profilin, were used as target allergens (TA). This retrospective study included 1059 subjects, (396 males and 663 females, mean age 42.8 years). The current study showed that sensitization to a pan-allergen entails higher odds to have other sensitizations. In addition, the co-sensitization pattern depends on the basis of the sensitizing pan-allergen family. LTP-sensitization is strongly associated with peanut sensitization, PR10 and profiling sensitization with hazelnut positivity. This study shows that a pan-allergen sensitization is frequently associated with co-sensitizations and the sensitization pattern depends on the sensitizing pan-allergen.
Review suggests that the immunoregulatory and anti‐inflammatory properties of allergenic foods can provoke oral tolerance if introduced early to infants’ diets.
For years, the advice was to postpone introducing allergenic foods, in order to prevent food allergies. However, food allergies have escalated rather than declined and our review of the latest epidemiological, immunological and nutritional research suggests that early weaning practices may be beneficial. The most allergenic foods, such as fish, eggs and peanuts, have proved to be inherently rich in tolerogenic substances that can play a significant role in preventing allergies. CONCLUSION: We found evidence that the immunoregulatory and anti-inflammatory properties of allergenic foods can provoke oral tolerance if introduced early to both low-risk and high-risk infants.