Rapidly detecting major peanut allergen-Ara h2 in edible oils using a new immunomagnetic nanoparticle-based lateral flow assay.
Ara h2 is a major peanut allergen that induces rashes, vomiting, diarrhea, and anaphylactic shock. Since peanut is a major source in producing edible oils globally, Ara h2 residues can be present in various edible oils. In this work, an immunomagnetic nanoparticle-based lateral flow assay for identifying Ara h2 in edible oils is developed. This assay exhibits high sensitivity with a visual detection limit of 0.1 mg/kg Ara h2 in oil, and favorable specificity in differentiating peanut from seeds and nuts. The calculated CV values of intra- and inter-assay were 6.73-10.21% and 4.75-8.57%, respectively, indicating high reproducibility. In an analysis of 26 oil products, Ara h2 was detected in two peanutoils as 0.122 ± 0.026 mg/kg and 0.247 ± 0.027 mg/kg. The entire method takes 5 h, including a 3.5-h sample preparation. Hence, this method has the potential to be an effective way to screen edible oils for Ara h2.
Effects of different thermal processing methods on the structure and allergenicity of peanut allergen Ara h 1.
Boiling and frying can alter the structure of peanut allergens and therefore change the IgE-binding capacity of the Ara h 1. In this research, we aim to clarify the connections between structural changes and the allergenicity alteration, and recommend an effective thermal method to minimize the allergenicity of Ara h 1. Anion exchange chromatography was used to isolate Ara h 1 from non/heat-treated peanuts. Ara h 1 in boiled peanuts has a relatively low hydrophobic index, reduced maximum emission wavelength in the fluorescence, less content of α-helix, and the lowest IgE-binding efficiency. On the contrary, Ara h 1 in fried peanuts present a much higher degeneration degree, a red shift in fluorescence, and a decrease in the content of α-helix. These data indicate that boiling can reduce the allergenicity of Ara h 1, thus can be utilized in peanut processing from a security point of view.
Long-term Outcome of Peanut Oral Immunotherapy Facilitated Initially by Omalizumab.
BACKGROUND: We successfully used omalizumab to faciliate peanut oral immunotherapy (OIT) in children with reactivity to ≤50mg peanut protein and with high peanut-IgE (median 229 kU/L). OBJECTIVE: We report on long-term OIT outcomes in these patients, including dosing changes, adverse events, peanut immunoglobulin changes and quality of life (QoL). METHODS: Patients were followed for up to 72 months (67 months maintenance). Outcomes were collected on peanut dose amount, form and frequency, as well as adverse events, (QoL), and laboratory studies. RESULTS: Of 13 patients initially enrolled, 7 patients (54%) continued on peanut OIT through month 72; 6 (46%) discontinued therapy because of adverse reactions. Maintenance peanut protein dose varied between 500-3,500mg. Most patients consumed different peanut-containing products. All patients experienced at least one adverse event, and one patient developed eosinophilic eosphagitis. Peanut- IgE, Arah1-IgE and Arah2-IgE, peanut-SPT, Peanut-IgE:IgE ratio, and Arah2-IgE:Arah2-IgG4 ratio decreased on OIT. Peanut-IgG4, Arah1-IgG4, Arah2-IgG4 initially increased on OIT then decreased, though not falling to baseline levels. In patients who stopped OIT, there was a trend for reversal of these biomarker changes. Higher peanut-IgE and Arah2-IgE at study month 12 was associated with discontinuation. Patient and parent QoL improved from baseline, even in patients who discontinued OIT. CONCLUSION: While adjunctive omalizumab allowed for faster and successful desensitization in patients with high peanut-IgE, almost half of patients discontinued OIT within 72 months because of reactions. Patients who stopped therapy had higher month 12 peanut-IgE and Arah2-IgE. It is possible that these patients might benefit from longer omalizumab administration.
Early introduction of foods to prevent food allergy.
Food allergy is a growing public health problem, and in many affected individuals, the food allergy begins early in life and persists as a lifelong condition (e.g., peanut allergy). Although early clinical practice guidelines recommended delaying the introduction of peanut and other allergenic foods in children, this may have in fact contributed to the dramatic increase in the prevalence of food allergy in recent decades. In January 2017, new guidelines on peanut allergy prevention were released which represented a significant paradigm shift in early food introduction. Development of these guidelines was prompted by findings from the Learning Early About Peanut Allergy study-the first randomized trial to investigate early allergen introduction as a strategy to prevent peanut allergy. This article will review and compare the new guidelines with previous guidelines on food introduction, and will also review recent evidence that has led to the paradigm shift in early food introduction.
Peanut allergy–individual molecules as a key to precision medicine.
Peanut allergy is one of the most severe food allergies affecting millions of individuals worldwide. In German-speaking countries, peanutallergy is the most important cause of anaphylaxis in children and adolescents. This Editorial highlights the impact of individual peanutallergens on the severity of symptoms and summarizes the allergens' biological characteristics and usefulness as tools for precision diagnostic tests.
Food Allergy: A Comprehensive Population-Based Cohort Study.
OBJECTIVE: To determine the incidence and temporal trends of food allergies. PATIENTS AND METHODS:
We performed a historical cohort study to describe the epidemiology of food allergies among residents of all ages in Olmsted County, Minnesota, during a 10-year period from January 2, 2002, through December 31, 2011, using the Rochester Epidemiology Project database. Overall incidence and trends in biannual incidence rates over time were evaluated. RESULTS: During the 10-year study period, 578 new cases of food allergies were diagnosed. The average annual incidence rate was significantly higher among males compared with females (4.1 [95% CI, 3.6-4.5] vs 3.0 [95% CI, 2.7-3.4]; P<.001; per 10,000 person-years; 3.6 per 10,000 person-years overall). The pediatric incidence rate of food allergy increased from 7.0 (95% CI, 6.2-8.9) to 13.3 (95% CI, 10.9-15.7) per 10,000 person-years between the 2002-2003 and 2006-2007 calendar periods and then stabilized at 12.5 and 12.1 per 10,000 person-years in the last 2 calendar periods. Milk, peanut, and seafood were the most common allergen in infancy, in children between ages 1 and 4 years, and in the adult population, respectively. CONCLUSION: This is one of the first population-based studies to examine the temporal trends of food allergies. The incidence of food allergies increased markedly between 2002 and 2009, with stabilization afterward. Additional longitudinal studies are warranted to assess for epidemiological evidence of changes in food allergy incidence with changing recommendations for allergenic food introduction.
Release of Major Peanut Allergens from Their Matrix under Various pH and Simulated Saliva Conditions—Ara h2 and Ara h6 Are Readily Bio-Accessible.
The oral mucosa is the first immune tissue that encounters allergens upon ingestion of food. We hypothesized that the bio-accessibility of allergens at this stage may be a key determinant for sensitization. Light roasted peanut flour was suspended at various pH in buffers mimicking saliva. Protein concentrations and allergens profiles were determined in the supernatants. Peanut protein solubility was poor in the pH range between 3 and 6, while at a low pH (1.5) and at moderately high pHs (>8), it increased. In the pH range of saliva, between 6.5 and 8.5, the allergens Ara h2 and Ara h6 were readily released, whereas Ara h1 and Ara h3 were poorly released. Increasing the pH from 6.5 to 8.5 slightly increased the release of Ara h1 and Ara h3, but the recovery remained low (approximately 20%) compared to that of Ara h2 and Ara h6 (approximately 100% and 65%, respectively). This remarkable difference in the extraction kinetics suggests that Ara h2 and Ara h6 are the first allergens an individual is exposed to upon ingestion of peanut-containing food. We conclude that the peanut allergens Ara h2 and Ara h6 are quickly bio-accessible in the mouth, potentially explaining their extraordinary allergenicity.
Feasibility of desensitizing children highly allergic to peanut by high‐dose oral immunotherapy.
BACKGROUND: There is limited data on feasibility, efficacy and safety of high-dose oral immunotherapy (OIT) in children highly allergic to peanuts. OBJECTIVE: In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000 mg peanut protein or alternatively, a lower individual maintenance dose (IMD), by OIT up-dosing. Secondarily, we aimed to identify adverse events (AEs), and determine factors associated with reaching a maintenance dose. METHODS: The TAKE-AWAY peanut OIT trial enrolled 77 children 5-15 years -old, with a positive oral peanut challenge. Fifty-seven were randomized to OIT with bi-weekly dose step-up until reaching MMD or IMD, and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocol-deviations were explored for associations with reaching maintenance dose. RESULTS: All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s-IgG₄/s-IgE ratio (OR (95% CI)) 1.02 (1.00, 1.04) was associated with reaching MMD. CONCLUSION: Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25 - 5 g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited feasibility of reaching MMD.
Tree nut allergens.
Tree nuts are considered as part of a healthy diet due to their high nutritional quality. However, they are also a potent source of allergenic proteins inducing IgE mediated hypersensitivity often causing serious, life-threatening reactions. The reported prevalence of tree nut allergy is up to 4.9% worldwide. The general term "tree nuts" comprises a number of nuts, seeds, and drupes, derived from trees from different botanical families. For hazelnut and walnut several allergens have been identified which are already partly applied in component resolved diagnosis, while for other tree nuts such as macadamia, coconut, and Brazil nut only individual allergens were identified and data on additional allergenic proteins are missing. This review summarizes the current knowledge on tree nut allergens and describes their physicochemical and immunological characterization and clinical relevance.
Evidence of Cross-Reactivity between Different Seed Storage Proteins from Hazelnut (Corylus avellana) and Walnut (Juglans regia) Using Recombinant Allergen Proteins.
Seed storage proteins are extremely stable allergens in nuts, seeds, and legumes and are responsible for the most severe allergic reactions to these foods. The cross-reactivity between seed storage proteins from different sources has not been studied at a molecular level so far. This study aimed to ascertain the cross-reactivity between walnut and hazelnut seed storage proteins using recombinant allergens. Sera from 13 consecutive patients with severe primary walnut and/or hazelnut allergy and hypersensitive to both nuts were studied. IgE specific for rCor a 9, rCor a 14, and rJug r 1 was measured, and inhibition experiments were carried out by measuring IgE reactivity after absorption of patients' sera with freshly prepared walnut extract. All 13 sera showed strong IgE reactivity against walnut 2S albumin, Jug r 1, 12 reacted to hazelnut 2S albumin, Cor a 14, and 8 to the hazelnut legumin, Cor a 9. In inhibition experiments, absorption of sera with whole walnut extract led to the complete disappearance of IgE reactivity to Jug r 1 in 12/13 cases, as expected, but also to the complete disappearance of specific IgE to Cor a 14 in 9/12 sera, and of IgE reactivity to Cor a 9 in 7/8. In the remaining cases a dramatic drop in IgE reactivity was observed. The study shows that patients primarily allergic to either walnut or hazelnut showing a skin or serological reactivity to the other nut also are potentially at risk of severe allergic reactions caused by cross-reactivity between 2S albumins and legumins.