Latest Developments in the Management of Nut Allergies.
Purpose of review. In this review, we sought to describe the most recent advances in the dietary and medical management of peanut and tree nut allergy, including selective introduction and immunotherapy. Recent findings. Dietary updates include changes to labeling laws, improved information sources, and new apps for buying foods in shops and overseas to better protect individuals with nut allergies. There are still issues in the management of nut allergies in schools, such as parents having to resort to packed lunches instead of school meals and patients experiencing bullying. Air travel also poses concern, but additional resources are now available to travelers, and recent evidence suggest limited airborne exposure to nuts. The medical management of anaphylaxis is use of epinephrine; however, this remains underutilized. Needle length and administration devices have been recently debated considering the risk of bone penetration vs subcutaneous administration, and autoinjectors seem to deliver higher peak concentrations than syringes. Selective nut introduction has gained momentum in the last 5 years, demonstrating improved quality of life but with the need for motivated parents for continued consumption and available resources for challenges. Immunotherapy to nuts is also a rapidly developing field, with the balance of efficacy and safety being important considerations in the differing modes of administration. Summary. The management of nut allergies is a rapidly developing field, and dietary and medical management have progressed significantly in the last 5 years. Future research directions include improving safety and efficacy of food immunotherapy and examining patients’ goals for therapy and treatment outcomes. https://doi.org/10.1007/s40521-021-00290-2
Electrochemical and optical biosensing platforms for the immunorecognition of hazelnut Cor a 14 allergen
Two immunosensors were advanced to target hazelnut Cor a 14 based on electrochemical and optical transduction. Both approaches were developed with two types of custom-made antibodies, namely anti-Cor a 14 IgG (rabbit) and anti-Cor a 14 IgY (hen's egg) targeting the Cor a 14 allergen. Antibody immobilisation was performed via EDC/NHS onto disposable screen-printed electrodes. The detection limit (LOD) of the electrochemical immunoassay for Cor a 14 was 5-times lower than the optical, being down to 0.05 fg mL-1 with a dynamic range of 0.1 fg mL-1 to 0.01 ng mL-1. Antibody selectivity was verified against non-target 2S albumins (potential cross-reactive plant species). Anti-Cor a 14 IgY exhibited the best specificity, presenting minor cross-reactivity with peanut/walnut. Preliminary results of the application of anti-Cor a 14 IgY electrochemical immunosensor to incurred foods established a LOD of 1 mg kg-1 of hazelnut in wheat (0.16 mg kg-1 hazelnut protein).
https://doi.org/10.1016/j.foodchem.2021.130122
Unusual and Unexpected Allergic Reactions Can Be Unraveled by Molecular Allergy Diagnostics
The fifth class of immunoglobulin, immunoglobulin E (IgE) was discovered in 1967 and has had immense importance for the understanding, diagnosis, and treatment of allergic disease. More than 50 years have passed and efforts to characterize, standardize, and refine allergens with the aim to improve clinical diagnosis and allergen-specific immunotherapy are still ongoing. Another important breakthrough was made in 1999 with the introduction of component-resolved diagnostics (CRD), making it possible to quantify IgE antibodies against individual allergen proteins for diagnostic purposes at a molecular level. The progress and developments made in allergy diagnosis often originate from clinical observations and case studies. Observant physicians and health-care personnel have reported their findings in the medical literature, which in turn has inspired researchers to become involved in clinical research. Allergists continuously encounter new allergies and are often asked by their patients how to prevent new reactions. In the current article, we focus on recent clinical observations that can now be explained by CRD. The examples taken concern allergic reactions toward peanuts, tree nuts, lemon kernels, health drinks, meat, insects, dog dander, cannabis, and semen. We now have an improved understanding of why patients may react in a serious or unexpected way, as illustrated by these examples, yet many other clinical observations remain unexplained. The aim of this review is to highlight the importance of clinical observations among allergic patients, focusing on systemic, or unusual and unexpected allergic reactions, where component-testing has further refined the diagnosis of IgE-mediated allergy.
https://doi.org/10.1159/000515708
Peanut and hazelnut occurrence as allergens in foodstuffs with precautionary allergen labeling in Canada.
Precautionary allergen labeling (PAL) is widely used by food industries. Occurrence studies revealed that few analyzed products contained the allergen(s) present in the statement, but little is known in Canada. To improve manufacturing practices and better manage allergen cross-contamination, occurrence data is needed to determine the exposure of allergic individuals eating those products. Samples were analyzed for peanuts (n = 871) and hazelnuts (n = 863) using ELISA methods. Within samples analyzed for peanuts, 72% had a PAL (n = 628), 1% had peanuts as a minor ingredient (n = 9) and 27% were claimed "peanut-free" (n = 234). Most hazelnut samples had a PAL for tree nuts/hazelnuts (94%; n = 807) with 6% claimed "nut-free" (n = 56). Peanuts and hazelnuts were found in 4% (0.6-28.1 ppm) and 9% (0.4-2167 ppm) of all samples, respectively. Chocolates were mostly impacted; they should be treated apart from other foods and used in risk assessments scenarios to improve manufacturing practices, reducing unnecessary PAL use.
https://doi.org/10.1038/s41538-021-00093-4
Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study
Background: Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. Objective: To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. Methods: This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Results: Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non-IgE mediated in 15.5%, and mixed IgE/non-IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0-2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13-18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non-IgE-mediated FA in multivariate regression analysis. Conclusion: This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.
https://doi.org/10.2500/aap.2021.42.210005
Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.
Background: The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis; yet the immunologic mechanism of this strain's susceptibility is not known. Objective: We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain as both genes have been associated with food allergy. Methods: We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome and biomarkers of gut permeability. Results: In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis following oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring TLR4 or DOCK8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice when compared with C57BL/6 mice, which correlated with increased number of goblet cells in the small intestine. Conclusions: Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens and that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.
https://doi.org/10.1016/j.jaci.2021.05.015
Accurate and reproducible diagnosis of peanut allergy using epitope mapping
Background: Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts. Methods: The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years. Results: In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%. Conclusions: In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing.
https://doi.org/10.1111/all.14905
A positive feedback loop reinforces the allergic immune response in human peanut allergy.
Food allergies are a leading cause of anaphylaxis, and cellular mechanisms involving antigen presentation likely play key roles in their pathogenesis. However, little is known about the response of specific antigen-presenting cell (APC) subsets to food allergens in the setting of food allergies. Here, we show that in peanut-allergic humans, peanut allergen drives the differentiation of CD209+ monocyte-derived dendritic cells (DCs) and CD23+ (FcєRII) myeloid dendritic cells through the action of allergen-specific CD4+ T cells. CD209+ DCs act reciprocally on the same peanut-specific CD4+ T cell population to reinforce Th2 cytokine expression in a positive feedback loop, which may explain the persistence of established food allergy. In support of this novel model, we show clinically that the initiation of oral immunotherapy (OIT) in peanut-allergic patients is associated with a decrease in CD209+ DCs, suggesting that breaking the cycle of positive feedback is associated with therapeutic effect.
https://doi.org/10.1084/jem.20201793
Increased Rates of Peanut and Tree Nut Aspiration as a Possible Consequence of Allergy Prevention by Early Introduction
Background: Pediatric airway foreign bodies (FBs) are a surgical emergency, and peanuts and tree nuts (PN/TNs) can pose a significant aspiration risk in young children. In 2015, the Learning Early About Peanut allergy (LEAP) trial established that early introduction of peanuts in high-risk infants reduced the risk of developing a peanut allergy. Infant feeding guidelines were subsequently modified to actively encourage the introduction of allergenic foods for all infants. The impact of this shift in feeding advice on the incidence of PN/TN inhalation has not been previously studied. Objective: To determine the incidence of PN/TN inhalation presentations to a quaternary pediatric hospital between 2008 and 2018. Methods: A retrospective cohort study of children who were diagnosed with an airway FB by rigid bronchoscopy. Results: There were 200 cases of FB inhalation (35% PN/TN, 34% other foods, and 31% inorganic material). There was a rise in the total incidence of FB inhalation over the study period (incidence ratio rate [IRR], 1.09; P < .001). The rise was due to PN/TN (IRR, 1.16; P < .002) and other food inhalation (IRR, 1.12; P = .01), with no significant increase in inorganic FB aspiration (IRR, 1; P = .94). Between pre-LEAP (2008-2014) and post-LEAP (2015-2018) periods, there was a trebling, doubling, and no increase in the rate of PN/TN, other food, and inorganic FB inhalation, respectively. Conclusions: Since the publication of the LEAP study, there has been a rise in PN/TN and other hard solid food inhalation at our institution. This study highlights the urgent need to engage the public to promote safe introduction of hard foods in young children.
https://doi.org/10.1016/j.jaip.2021.03.052