Updated population minimal eliciting dose distributions for use in risk assessment of 14 priority food allergens.
Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were published for 11 allergenic foods in 2014. Systematic data collection has continued (2011-2018) and the dataset now contains over 3400 data points. The current study provides new and updated EDp values for 14 allergenic foods and incorporates a newly developed Stacked Model Averaging statistical method for interval-censored data. ED01 and ED05 values, the doses at which 1%, and respectively 5%, of the respective allergic population would be predicted to experience any objective allergic reaction were determined. The 14 allergenic foods were cashew, celery, egg, fish, hazelnut, lupine, milk, mustard, peanut, sesame, shrimp (for crustacean shellfish), soy, walnut, and wheat. Updated ED01 estimates ranged between 0.03 mg for walnut protein and 26.2 mg for shrimp protein. ED05 estimates ranged between 0.4 mg for mustard protein and 280 mg for shrimp protein. The ED01 and ED05 values presented here are valuable in the risk assessment and subsequent risk management of allergenic foods.
Identification and in silico bioinformatics analysis of PR10 proteins in cashew nut.
Proteins from cashew nut can elicit mild to severe allergic reactions. Three allergenic proteins have already been identified, and it is expected that additional allergens are present in cashew nut. PATHOGENESIS-RELATED PROTEIN 10 (PR10) allergens from pollen have been found to elicit similar allergic reactions as those from nuts and seeds. Therefore, we investigated the presence of PR10 genes in cashew nut. Using RNA-seq analysis, we were able to identify several PR10-like transcripts in cashew nut and clone six putative PR10 genes. In addition, PR10 protein expression in raw cashew nuts was confirmed by immunoblotting and LC-MS/MS analyses. An in silico allergenicity assessment suggested that all identified cashew PR10 proteins are potentially allergenic and may represent three different isoallergens.
A Single Monoclonal Antibody against the Peanut Allergen Ara h 2 Protects against Systemic and Local Peanut Allergy.
Background: Peanut allergy is the most prevalent and dangerous food allergy. Peanuts consist of a large number of different allergens and peanut-allergic patients are frequently sensitized to multiple allergens. Hence, conventional desensitization approaches aim at targeting as many allergens as possible. Methods: The monoclonal anti-Ara h 2 antibody (mAb) was produced by hybridoma cells derived from WT BALB/c mice after immunization with a vaccine based on virus-like particles coupled to Ara h 2. BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to alum and mAbs were applied i.v. Challenge was performed the next day with the whole peanut extract intravenously and via skin prick test. Results: Here we show in peanut-allergic mice that a single high-affinity mAb specific for Ara h 2 is able to block systemic and local allergic reactions induced by the complex peanut extract. We confirm in vitro binding of the mAb to the inhibitory low-affinity FcγRIIb receptor using a sensitive biosensor and demonstrate in vivo that protection was dependent on FcγRIIb. Conclusion: A single mAb specific for Ara h 2 is able to improve local and systemic allergic symptoms induced by the whole allergen mixture.
Can my child with IgE‐mediated peanut allergy introduce foods labeled with “may contain traces”?.
Peanut IgE-mediated food allergy is one of the most common food allergies in children with a prevalence that has increased in the past decades in westernized countries. Peanut allergies can trigger severe reactions and usually persist over time. Peanut-allergic children and their families are often confronted to processed foods with precautionary allergen labeling (PAL) such as "may contain traces of peanuts", which are frequently used by the food industry. Patients are generally confused as to whether eating such foods entails a risk of allergic reaction, which can ultimately lead to dietary restrictions and decreased quality of life. Thus, guidance towards eviction of foods with PALs such as "may contain traces of peanuts" is a recurring problem that peanut-allergic patients address during pediatric allergy consultations with varying attitudes among allergists. Many studies have evaluated peanut contamination in foods with PALs, with generally less than 10% of foods containing detectable levels of peanuts, albeit heterogeneous amounts, with in rare occasions levels that could trigger allergic reactions in certain patients. The risk of reacting to foods with traces varies significantly with threshold, with patients with the lowest reaction thresholds at highest risk, and a dramatic reduction of risk as threshold increases. Thus, risk stratification based on individual reaction threshold may help stratify patients' risk of reacting to foods with PAL. In clinical practice, a single dose 30 mg peanut protein oral food challenge may be an option to stratify peanut-allergic patients' risk when introducing foods with PAL, as illustrated by 3 clinical cases.
Tree Nuts Anaphylaxis in Preschool Age Children.
Introduction. The incidence of food-induced anaphylaxis (FIA) is increasing in young children. Although the commonest culprits are cow's milk and egg, FIA to tree nuts (TNs) have been increasing. Objective. Characterization of children referred to our allergy department due to TNs-induced anaphylaxis (TNs-FIA) during preschool age. Materials and methods. We have retrospectively included 25 children with clinical history of preschool TNs-FIA, proven by allergological work-up. TNs sensitization was assessed by skin prick tests and/or specific IgE. Results. The mean age of the first anaphylactic episode was 3.1±1.2 years. The majority (92%) had an allergic disease (52% asthma). The implicated TNs were cashew (11 children), walnut (8), pine nut (5), hazelnut (2) and almond (1). The reaction occurred after the first known ingestion in 68%. In 92%, symptoms appeared within 30 minutes after exposure. The most frequent clinical symptoms were mucocutaneous (96%), respiratory (80%) and gastrointestinal (52%). Twenty-one children were admitted to the emergency department, although only 48% were treated with epinephrine. An underneath IgE-mediated mechanism was proven in all cases. Immunologic cross-reactivity with other TNs was identified in 84%, and with peanut in 36%. Overall, in our center, TNs-FIA represents 18% of all causes of FIA. Conclusions. In preschool age children with TNs-FIA, cashew and walnut were the commonest implicated nuts. Most reactions occurred briefly after exposure to minimal amounts of TNs, demonstrating the high potency of these allergens. About one-third also had peanut sensitization. Potentially life-threatening TNs allergy can occur early in childhood and adequate management should be undertaken.
A 5-year retrospective review of children with peanut allergy in the largest paediatric hospital in Singapore.
Background: The prevalence of peanut allergy (PA) among children has increased significantly over the past decade. Even though the prevalence of PA in Singapore is considered low, peanut is the top trigger for food-induced anaphylaxis in Singaporean children. Objective: To describe the demographic characteristics and clinical features of children with PA. Methods: This is a 5-year retrospective review of children diagnosed with PA based on clinical history coupled with a positive skin prick test to peanut or positive oral food challenge results. Results: There were 269 patients (53.9% males) with a clinical diagnosis of PA. The median age at first allergic presentation for the PA group was 24 months old, with interquartile range of 13-39 months. The most common form of peanut introduced was roasted peanut. The rate of peanut anaphylaxis was 7.1%. Concomitant tree nut sensitization was found in 32.3% of this cohort, predominantly to cashew nut. Majority of them have a personal history of atopy - 75.8% with eczema, 63.6% with allergic rhinitis, and 19.7% with asthma. Conclusion: This is the first large review of peanut-allergic children in Singapore. Prospective population-based studies are needed to establish the true prevalence and risk factors associated with the development of this potentially life-threatening condition.
Predictive factors of allergy to pistachio in children allergic to cashew nut.
Background: Cashew nut (CN) allergy prevalence has increased over the last few years. In children allergic to CN, complete avoidance of pistachio is usually recommended, but recent study showed that only one third of children allergic to CN were also allergic to pistachio. The aim of our study was to identify predictive factors of allergy to pistachio in children allergic to CN. Methods: All children who had a positive oral food challenge (OFC) to CN between November 2013 and October 2017 in the Paediatric Allergy Department of the University Hospital of Nancy were included. Logistic regression models were used to predict the probability of allergy to pistachio. Results: Among the 147 children included, tolerance or allergy to pistachio was known for 51. Out of these, 40 were allergic to pistachio (78.4%). Children allergic to pistachio had a larger weal size of skin prick test to CN (P = .01) and pistachio (P = .0007) and a lower reaction dose to CN (P < .0001). In multivariate analysis, only the reaction dose to CN was significantly associated with allergy to pistachio. Children with a low reaction dose to CN were significantly more at risk to have an allergy to pistachio (P = .01). Conclusion: A low reaction dose to CN seems to be a predictive factor of allergy to pistachio in children allergic to CN. In order to limit unnecessary food eviction, a pistachio OFC should be performed in children having high reaction dose whatever the importance of the skin or the specific IgE sensitization to pistachio.
Immunoglobulin E-Mediated Food Allergies Differ in East Mediterranean Children Aged 0–2 Years.
Objective: Precise diagnosis of allergy requires knowledge of the population's food allergy (FA) spectrum and predictors. Methods: Medical charts of Turkish children aged 0-2 years with FA and/or atopic dermatitis (AD) were reviewed. Results: A total of 1,389 patients, 912 with FA and 1,140 with AD, were included. In the FA group, the most frequently diagnosed FAs were egg white (75.9%), cow's milk (55.7%), tree nuts (31.5%) and sesame (20.6%). The detection of FA in 99% of children with any kind of FA necessitate testing with egg white, cow's milk, hazelnut, sesame, walnut, cashew, and pistachio. In the FA group, 72.7 and 56.8% had AD and multiple FA respectively. Multiple FA (56.8 vs. 49.8%) and hen's egg allergy (85.5 vs. 50.2%, p < 0.005) were more common and cow's milk allergy (51.4 vs. 67.1%, p < 0.005) less common in the AD subgroup of the FA group than in the non-AD subgroup. Multiple FA likelihood increases parallel to the severity of AD (p < 0.05). In the AD group, 58.2% had an immunoglobulin E-mediated FA. The risk of concomitant FA increased as the age at symptom onset of AD decreased (OR 0.800 [95% CI 0.731-0.875]; p < 0.001) and the severity of AD increased (OR 2.350 [95% CI 1.898-2.911]; p < 0.001). Conclusion: Although severe and early-onset AD is a predictor of the presence and magnitude of FA in infancy, the spectrum of FA is a reflection of cultural characteristics. The clinical presentations of both AD and FA may in fact be an expression of the extent of the immune dysregulation underlying atopy and allergy.
Children with nut allergies have impaired gene expression of toll‐like receptors pathway.
Background: Trends in food allergies prompted investigation into the underlying mechanisms. Genetic and epigenetic factors are of high interest and, in particular, the interplay between genes relating to immune factors directly and indirectly involved in food allergy pathogenesis. We sought to determine potential links between gene expression and epigenetic factors relating to Toll-like receptor (TLR) pathways and childhood food allergies. Methods: In a cross-sectional study, samples from 80 children with and without food allergies were analysed for gene expression, DNA methylation, and a range of immune factors relating to TLR pathways. TLR2, TLR4, CD14, IL5, IL13 and vitamin D were explored. Results: The importance of these immune factors appeared to vary between the differing types of food allergies. Expression of TLR2 (p<0.001), TLR4 (p=0.014) and CD14 (p=0.028) varied significantly between children with no food allergy, allergy to nuts and peanuts, and allergy to eggs. DNA methylation in the promoter regions of these genes had a significant association with gene expression. These trends persisted when subjects were stratified by nut allergy versus no nut allergy. Furthermore, TLR2 (p=0.001) and CD14 (p=0.007) expression were significantly lower in children with food allergies when compared to those without. Conclusion: Gene expression of TLR pathway genes was directly related to food allergy type, and DNA methylation had an indirect effect. TLR2 pathways are of significant interest in nut allergies.
A genome-wide identification, characterization and functional analysis of salt-related long non-coding RNAs in non-model plant Pistacia vera L. using transcriptome high throughput sequencing.
Long non-coding RNAs (lncRNAs) play crucial roles in regulating gene expression in response to plant stresses. Given the importance regulatory roles of lncRNAs, providing methods for predicting the function of these molecules, especially in non-model plants, is strongly demanded by researchers. Here, we constructed a reference sequence for lncRNAs in P. vera (Pistacia vera L.) with 53220 transcripts. In total, we identified 1909 and 2802 salt responsive lncRNAs in Ghazvini, a salt tolerant cultivar, after 6 and 24 h salt treatment, respectively and 1820 lncRNAs in Sarakhs, a salt sensitive cultivar, after 6 h salt treatment. Functional analysis of these lncRNAs by several hybrid methods, revealed that salt responsive NAT-related lncRNAs associated with transcription factors, CERK1, LEA, Laccase genes and several genes involved in the hormone signaling pathways. Moreover, gene ontology (GO) enrichment analysis of salt responsive target genes related to top five selected lncRNAs showed their involvement in the regulation of ATPase, cation transporter, kinase and UDP-glycosyltransferases genes. Quantitative real-time PCR (qRT-PCR) experiment results of lncRNAs, pre-miRNAs and mature miRNAs were in accordance with our RNA-seq analysis. In the present study, a comparative analysis of differentially expressed lncRNAs and microRNA precursors between salt tolerant and sensitive pistachio cultivars provides valuable knowledge on gene expression regulation under salt stress condition.