Risk Factor For Peanut Allergy Research Articles

Different airborne particulates trigger distinct immune pathways leading to peanut allergy in a mouse model.

Environmental exposure to peanut through non-oral routes is a risk factor for peanut allergy. Early-life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model. C57BL/6J mice were co-exposed to peanut and either urban particulate matter (UPM) or diesel exhaust particles (DEP) via the airways and assessed for peanut sensitization and development of anaphylaxis following peanut challenge. Peanut-specific CD4+ T helper (Th) cell responses were characterized by flow cytometry and Th cytokine production. Mice lacking select innate immune signaling genes were used to study mechanisms of PM-induced peanut allergy. Airway co-exposure to peanut and either UPM- or DEP-induced systemic sensitization to peanut and anaphylaxis following peanut challenge. Exposure to UPM or DEP triggered activation and migration of lung dendritic cells to draining lymph nodes and induction of peanut-specific CD4+ Th cells. UPM- and DEP-induced distinct Th responses, but both stimulated expansion of T follicular helper (Tfh) cells essential for peanut allergy development. MyD88 signaling was critical for UPM- and DEP-induced peanut allergy, whereas TLR4 signaling was dispensable. DEP-induced peanut allergy and Tfh-cell differentiation depended on IL-1 but not IL-33 signaling, whereas neither cytokine alone was necessary for UPM-mediated sensitization. Environmental co-exposure to peanut and PM induces peanut-specific Tfh cells and peanut allergy in mice.

A Survey of Canadian Dietitians on Identification of Infants at High Risk of Food Allergy and Frequency of Allergenic Food Consumption.

Purpose: To assess knowledge of Canadian dietitians on the topics of food allergy and food allergy prevention guidelines, including introduction of allergenic solids to infants at risk of food allergy.Methods: An online survey was distributed via email listservs targeting Canadian dietitians.Results: In total, 144 of 261 dietitians completed the survey (60.5%). Respondents recommend introduction of peanut (89.5%) and allergenic solids (91.2%) within the recommended age of 4-6 months for infants at high risk of food allergy, but only 26.2% recommend offering peanut three times per week once it has been introduced. In identifying what constitutes an infant at high risk of developing peanut allergy, dietitians expressed lower comfort levels and lower number of correct responses.Conclusions: Dietitians demonstrated they are up to date regarding the timing of introduction of allergenic solids, but not the frequency of consumption once introduced, for infants at high risk of food allergy. They also expressed low comfort level identifying risk factors for peanut allergy. There are opportunities for further education of dietitians, as well as potential to further utilize dietitian services for the benefit of patients with food allergy or who are at risk for food allergy.

Early-life predictors and risk factors of peanut allergy, and its association with asthma in later-life: Population-based birth cohort study.

BackgroundUnderstanding risk factors for peanut allergy (PA) is essential to develop effective preventive measures.ObjectiveThe objective was to ascertain associates and predictors of PA, and the relationship between PA and asthma severity.MethodsIn a population‐based birth cohort, we investigated the association between objectively confirmed PA with early‐life environmental exposures, filaggrin (FLG)‐loss‐of‐function mutations and other atopic disease. We then examined the association of PA with longitudinal trajectories of sensitization, wheeze and allergic comorbidities, which were previously derived using machine learning. Finally, we ascertained the relationship between PA and asthma severity.ResultsPA was confirmed in 30/959 participants with evaluable data. In the multivariate analysis, eczema in infancy (OR = 4.4, 95% CI 1.5–13.2, p = 0.007), egg sensitization at age 3 years (OR = 9.7, 95% CI 3.3–29.9, p < 0.001) and early‐life cat ownership (OR = 3.0, 95% CI 1.1–8.4, p = 0.04) were independent associates of PA. In the stratified analysis among 700 participants with genetic information, in children with early‐life eczema there was no difference in FLG mutations between children with and without PA (3/18 [16.7%] vs. 42/220 [19.1%], p = 1.00). In contrast, among children without eczema, those with PA were almost eight times more likely to have FLG mutations (2/6 [33.3%] vs. 27/456 [5.9%], p = 0.049). We observed associations between PA and multiple allergic sensitization profiles derived using machine learning, with ~60‐fold increase in risk among individuals assigned to multiple early sensitization. PA was significantly associated with persistent wheeze (but not other wheeze phenotypes), and with trajectories of atopic disease characterized by co‐morbid persistent eczema and wheeze (but not with transient phenotypes). Children with PA were more likely to have asthma, but among asthmatics we found no evidence of an association between PA and asthma severity.ConclusionsPeanut allergy is associated with multiple IgE sensitization and early‐onset persistent eczema and wheeze. FLG loss‐of‐function mutations were associated with peanut allergy in children without eczema.

Age and Eczema Severity, but Not Family History, Are Major Risk Factors for Peanut Allergy in Infancy

Since the publication of the Learning Early About Peanut Allergy (LEAP) study in 2015 and the addendum guidelines for the prevention of peanut allergy in 2017, there has been controversy regarding the need and value of performing screening tests in infants at a high risk of developing peanut allergy.In the study, the researchers included 321 infants aged 4 to 11 months with no history of peanut ingestion, testing, or reaction and at least 1 of the following risk factors for the development of peanut allergy: moderate to severe eczema, another food allergy, and/or a first-degree relative with peanut allergy.After a careful history regarding risk factors and a physical examination focused on eczema severity, the infants underwent peanut skin-prick testing and, depending on the skin-prick test wheal size, a graded oral peanut challenge or an observed feeding with a full serving of peanut.The median age of the participants was 7.2 months, and 58% were boys. A total of 78 had eczema only, 11 had other food allergies only, 107 had a family history only, and 125 had multiple risk factors. Overall, 37 (11%) were found to have a peanut allergy, including 18% of 195 with eczema, 19% of 59 with other food allergies, and 4% of 201 with a family history. Only 1% of 115 with a family history and no eczema had a peanut allergy. Among those with eczema, older age (odds ratio [OR]: 1.3; 95% confidence interval [CI]: 1.04 to 1.68 per month), higher severity of atopic dermatitis (OR: 1.19; 95% CI: 1.06 to 1.34 per 5 points on the Scoring Atopic Dermatitis), Black (OR: 5.79; 95% CI: 1.92 to 17.4, compared with White), or Asian American race (OR: 6.98; 95% CI: 1.92 to 25.44) and suspected or diagnosed other food allergy (OR: 3.98; 95% CI: 1.62 to 9.80) were associated with peanut allergy.In the study, researchers found that peanut allergy is common in infants with moderate to severe eczema and/or a history of other food allergies, whereas family without eczema is not a major risk factor. This strongly suggests that there is value in screening those with significant eczema and/or other food allergies. Even within the first year of life, introduction at later ages is associated with a higher risk of peanut allergy among those with eczema, supporting introduction of peanut as early as possible.With this study, the authors provide new and valuable information on an important and timely topic. First, there is value in screening infants at high risk, especially those with severe eczema with or without other food allergies. Second, as was suggested by the LEAP study, earlier introduction appears to be important for these infants at the highest risk. The window of protection may truly be closing by 6 to 7 months of age. Third, and one of the most common questions encountered in day to day practice, family history of peanut allergy without other risk factors does not impart increased risk, providing reassurance that those infants to do need to be tested before peanut introduction.

A Synopsis of the Synopses, 2020–2021

A Synopsis of the Synopses, 2020–2021

History of Eczema Among Black and White Peanut Allergic Children

Eczema is a risk factor for peanut allergy (PA) development. Racial differences in eczema and food allergy outcomes exist. This study aims to explore potential racial differences in eczema history among peanut allergic children.

Age and eczema severity, but not family history, are major risk factors for peanut allergy in infancy

Whether to screen high-risk groups before early peanut introduction is controversial. We sought to determine the risk of peanut allergy (PA) before peanut introduction for infants with (1) moderate-severe eczema, (2) another food allergy (FA), and/or (3) a first-degree relative with peanut allergy (FH). Infants aged 4 to 11 months with no history of peanut ingestion, testing, or reaction and at least 1 of the above risk factors received peanut skin prick test and, depending on skin prick test wheal size, oral food challenge or observed feeding. A total of 321 subjects completed the enrollment visit (median age, 7.2 months; 58% males); 78 had eczema only, 11 FA only, 107 FH only, and 125 had multiple risk factors. Overall, 18% of 195 with eczema, 19% of 59 with FA, and 4% of 201 with FH had PA. Only 1% of 115 with FH and no eczema had PA. Among those with eczema, older age (odds ratio [OR], 1.3; 95% CI, 1.04-1.68 per month), higher SCORing Atopic Dermatitis score (OR, 1.19; 95% CI, 1.06-1.34 per 5 points), black (OR, 5.79; 95% CI, 1.92-17.4 compared with white), or Asian race (OR, 6.98; 95% CI, 1.92-25.44) and suspected or diagnosed other FA (OR, 3.98; 95% CI, 1.62-9.80) were associated with PA. PA is common in infants with moderate-severe eczema, whereas FH without eczema is not a major risk factor, suggesting screening only in those with significant eczema. Even within the first year of life, introduction at later ages is associated with a higher risk of PA among those with eczema, supporting introduction of peanut as early as possible.

The MALT1 locus and peanut avoidance in the risk for peanut allergy

The MALT1 locus and peanut avoidance in the risk for peanut allergy

A Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma

_To the Editor:_ Previously, we identified the HLA region as a risk factor forpeanut allergy (PA); this observation is supported further by 2 independent genome-wide association studies (GWASs). The HLA class II genes (including HLA-DR, HLA-DQ, and HLADP) encode molecules involved in presentation of extracellular antigens, such as peanut allergens, to T lymphocytes, which in turn mediates B-cell antibody production.We used the Canadian Peanut Allergy Registry (CanPAR) and the Busselton Health Study to conduct the largest GWAS for PA to date. Here we report analysis of the HLA region and a meta-analysis with data from 6 additional studies, which confirms and narrows the region of interest to HLA-DQB1 and establishes independence from asthma loci. [...]

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. We sought to investigate genetic susceptibility to PA. Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. Ameta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10-8), whereas SNPs associated with Src kinase-associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P ≤ 1.49 × 10-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P ≤ 1.49 × 10-6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (P = 7.50 × 10-11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P ≤ 1.49 × 10-6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30. This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

No impact of filaggrin deficiency on the efficacy of epicutaneous immunotherapy in a murine model

Background: Epicutaneous immunotherapy (EPIT®), currently investigated in the treatment of food allergy, needs the integrity of the skin to warrant safety and efficacy. Mutations in the gene encoding the key epidermal protein filaggrin (FLG) are risk factors for peanut allergy and disrupt the skin intergrity. We investigated the association between FLG deficiency and peanut EPIT® efficacy in a murine model. Methods: FLG mutant mice deficient in filaggrin (FLG-/-) or wild-type (WT) mice were sensitized with peanut protein extract (peanut protein) and cholera toxin. Sensitized mice received a patch per week during 8 weeks for EPIT®, using Viaskin®, and were then submitted to sustained peanut oral exposure. We assessed blood humoral and cellular responses and evaluated eosinophil infiltration in the gut mucosa. The different steps of allergen capture and transportation following deposition on the skin was also analyzed in sensitized mice. Results: Sensitization of mice was confirmed by a significant increase of specific Th2 biaised immunological responses. In sensitized mice, EPIT® significantly reduced IgE levels, splenocytes secretion of Th2 cytokines and recruitment of eosinophils in esophagus, compared to sensitized mice without epicutaneous immunotherapy. The allergen applied onto the skin of FLG-/- mice did not undergo passive skin passage or systemic delivery. Instead, the allergen was captured by skin CD205high DCs, which migrated to afferent lymph nodes, as already described in WT mice. Conclusions: EPIT® was efficient and safe in FLG-/- mice, suggesting that in Humans EPIT® keeps efficacy and safety in the presence of loss of function of FLG.

The Epidemiology of Food Allergy

The past few years have seen an exponential increase in publications on the topic of IgE-mediated food allergy. Recent publications have greatly advanced our understanding of the global prevalence of food allergy, and have revealed new insights into risk factors for food allergy. In this article, we will review these recent developments, summarise the current state of knowledge of the epidemiology of IgE-mediated food allergy, and outline areas of ongoing research where gaps in evidence remain. Recent publications reveal substantial differences in food allergy prevalence between countries. Data show that the incidence of food-induced anaphylaxis in developed countries continues to rise, particularly in children, although it remains unclear to what extent this is due to an increase in food allergy prevalence, or an increase in severe reactions among allergic individuals, or both. There has been considerable progress in understanding risk factors for food allergy. In particular, there is now good evidence that delayed introduction of peanut increases the risk of developing peanut allergy in infants with pre-existing risk factors for peanut allergy. A shift towards earlier introduction of peanut in these infants, now starting to be recommended in allergy prevention guidelines, may help to prevent peanut allergy in future generations. Recent studies have defined the prevalence of food allergy in different regions of the world. These studies provide strong baseline data to measure the extent to which new food allergy prevention strategies, including recommending timely peanut introduction for high-risk infants, change the prevalence of childhood food allergy.

Does LEAP change the screening paradigm for food allergy in infants with eczema?

The LEAP randomized controlled trial provides the first direct evidence that delayed introduction of peanut in an infant's diet significantly increases the risk of peanut allergy. However, as often is the case in ground-breaking research, the LEAP study raises almost as many questions as it resolves. Although the quality of design and excellence in study execution is unquestioned, the particular difficulty this study raises is how to generalize results from a trial of high-risk infants, which screened infants for the presence of peanut allergy prior to peanut introduction, to the general population. Although many existing infant feeding guidelines already allow for the introduction of allergenic foods from 4 to 6months of age irrespective of co-existent risk factors for peanut allergy, these will now need to be revised to more strongly state that avoidance may be harmful. Interim guidelines have already been published which incorporate these recommendations. However, the question as to how to achieve timely introduction of peanut into an infant's diet in a safe and cost-effective way, particularly in high-risk infants, remains unresolved.

Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy

BackgroundHistory and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy.ObjectiveWe sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk.MethodsPeanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study.ResultsThere was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01).ConclusionExposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA.

Predictive value of specific IgE for clinical peanut allergy in children: relationship with eczema, asthma, and setting (primary or secondary care)

The usefulness of peanut specific IgE levels for diagnosing peanut allergy has not been studied in primary and secondary care where most cases of suspected peanut allergy are being evaluated. We aimed to determine the relationship between peanut-specific IgE levels and clinical peanut allergy in peanut-sensitized children and how this was influenced by eczema, asthma and clinical setting (primary or secondary care). We enrolled 280 children (0–18 years) who tested positive for peanut-specific IgE (> 0.35 kU/L) requested by primary and secondary physicians. We used predefined criteria to classify participants into three groups: peanut allergy, no peanut allergy, or possible peanut allergy, based on responses to a validated questionnaire, a detailed food history, and results of oral food challenges.Fifty-two participants (18.6%) were classified as peanut allergy, 190 (67.9%) as no peanut allergy, and 38 (13.6%) as possible peanut allergy. The association between peanut-specific IgE levels and peanut allergy was significant but weak (OR 1.46 for a 10.0 kU/L increase in peanut-specific IgE, 95% CI 1.28-1.67). Eczema was the strongest risk factor for peanut allergy (aOR 3.33, 95% CI 1.07-10.35), adjusted for demographic and clinical characteristics. Asthma was not significantly related to peanut allergy (aOR 1.93, 95% CI 0.90-4.13). Peanut allergy was less likely in primary than in secondary care participants (OR 0.46, 95% CI 0.25-0.86), at all levels of peanut-specific IgE.The relationship between peanut-specific IgE and peanut allergy in children is weak, is strongly dependent on eczema, and is weaker in primary compared to secondary care. This limits the usefulness of peanut-specific IgE levels in the diagnosis of peanut allergy in children.

Antenatal risk factors for peanut allergy in children

BackgroundPrenatal factors may contribute to the development of peanut allergy. We evaluated the risk of childhood peanut allergy in association with pregnancy exposure to Rh immune globulin, folic acid and ingestion of peanut-containing foods.MethodsWe conducted a web-based case-control survey using the Anaphylaxis Canada Registry, a pre-existing database of persons with a history of anaphylaxis. A total of 1300 case children with reported peanut allergy were compared to 113 control children with shellfish allergy. All were evaluated for maternal exposure in pregnancy to Rh immune globulin and folic acid tablet supplements, as well as maternal avoidance of dietary peanut intake in pregnancy.ResultsReceipt of Rh immune globulin in pregnancy was not associated with a higher risk of peanut allergy (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.51 to 1.45), nor was initiation of folic acid tablet supplements before or after conception (OR 0.53, 95% CI 0.19 to 1.48). Complete avoidance of peanut-containing products in pregnancy was associated with a non-significantly lower risk of peanut allergy (OR 0.53, 95% CI 0.27 to 1.03).ConclusionThe risk of childhood peanut allergy was not modified by the following common maternal exposures in pregnancy: Rh immune globulin, folic acid or peanut-containing foods.Clinical implicationsRh immune globulin, folic acid supplement use and peanut avoidance in pregnancy have yet to be proven to modulate the risk of childhood anaphylaxis to peanuts.Capsule SummaryIdentification of prenatal factors that contribute to peanut allergy might allow for prevention of this life-threatening condition. This article explores the role of three such factors.

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Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

BackgroundIgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy.ObjectiveTo investigate the association between filaggrin loss-of-function mutations and peanut allergy.MethodsCase-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis.ResultsFilaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients (P = 3.0 × 10−6; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10−5; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis.ConclusionFilaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.

NEWS AND VIEWS: Government advice revised - early life exposure to peanut no longer a risk factor for peanut allergy

NEWS AND VIEWS: Government advice revised - early life exposure to peanut no longer a risk factor for peanut allergy

Maternal peanut exposure during pregnancy and lactation reduces peanut allergy risk in offspring

Maternal allergy is believed to be a risk factor for peanut allergy (PNA) in children. However, there is no direct evidence of maternal transmission of PNA susceptibility, and it is unknown whether maternal peanut exposure affects the development of PNA in offspring. To investigate the influence of maternal PNA on offspring reactions to the first peanut exposure, and whether maternal low-dose peanut exposure during pregnancy and lactation influences these reactions and peanut sensitization in a murine model. Five-week-old offspring of PNA C3H/HeJ mothers (PNA-Ms) were challenged intragastrically with peanut (first exposure), and reactions were determined. In a subset of the experiment, PNA-Ms were fed a low dose of peanut (PNA-M/PN) or not fed peanut (PNA-M/none) during pregnancy and lactation. Their 5-week-old offspring were challenged intragastrically with peanut, and reactions were determined. In another subset of the experiment, offspring of PNA-M/PN or PNA-M/none were sensitized with peanut intragastrically for 6 weeks, and serum peanut-specific antibodies were determined. PNA-M offspring exhibited anaphylactic reactions at first exposure to peanut that were associated with peanut-specific IgG(1) levels and prevented by a platelet activation factor antagonist. In a subset experiment, PNA-M/PN offspring showed significantly reduced first-exposure peanut reactions, increased IgG(2a), and reduced mitogen-stimulated splenocyte cytokine production compared with PNA-M/none offspring. In an additional experiment, PNA-M/PN offspring showed reduction of peanut-specific IgE to active peanut sensitization. We show for the first time maternal transmission of susceptibility to first-exposure peanut reactions and active peanut sensitization. Low-dose peanut exposure during pregnancy and lactation reduced this risk.