Development Of Peanut Allergy Research Articles

Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention.

A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption. Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months. We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 μg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 μg/l. Adverse events were uncommon, and the majority were related to the food challenge. Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).

Oral mucosa effectively protects against peanut allergy in mice

Oral consumption of peanut products early in life reduces the incidence of peanut allergy in children. However, little is known about whether exposure via the oral mucosa alone is sufficient, or if the gastrointestinal tract must be engaged to protect against peanut allergy. We used a mouse model and examined the effects of peanut allergen administration only to the oral cavity on allergy development induced by environmental exposure. Naïve BALB/c mice were administered peanut flour (PNF) sublingually, followed by epicutaneous exposure to PNF to mimic a human condition. The sublingual volume was adjusted to engage only the oral cavity and prevent it from reaching the esophagus or gastrointestinal tract. The efficacy was evaluated by examining the anaphylactic response, antibody titers, and T follicular helper (Tfh) cells. The mice exposed epicutaneously to PNF developed peanut allergy as demonstrated by increased plasma levels of peanut-specific IgE and the manifestation of acute systemic anaphylaxis upon intraperitoneal challenge with peanut extract. The development of peanut allergy was suppressed when mice had been given PNF sublingually before epicutaneous exposure. There were fewer Tfh cells in the skin-draining lymph nodes of mice that received sublingual PNF compared with PBS. Suppression of IgE production was observed with sublingual PNF at one-tenth of the intragastric PNF dose. Administration of peanut allergens only to the oral cavity effectively prevents the development of peanut allergy. The capacity of the oral mucosa to promote immunologic tolerance needs to be evaluated further to prevent food allergy.

A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice

The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, unlike C3H/HeJ (C3H) mice. To determine the genetic basis of orally-induced anaphylaxis to peanut in CC027 mice. A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 and five additional CC strains. Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis, and 4% having severe anaphylaxis. A total of eight genetic loci were associated with variation in response to peanut challenge, six associated with anaphylaxis (temperature decrease) and two associated with peanut-specific IgE levels. There were two major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis (thymocyte-expressed molecule involved in selection) gene. Consistent with Themis' described functions, we found that CC027 have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells. Our results demonstrate a key role for Themis in the orally-reactive CC027 mouse model of peanut allergy.

Optimising the management of peanut allergy by targeting immune plasticity.

Randomised controlled trials investigating the efficacy of oral tolerance induction to peanut have enabled detailed comparison of their clinical and immunological success. They have demonstrated that the regular consumption of peanut for at least 2 years by babies who are not allergic enables protection from developing peanut allergy. The LEAP study intervention tested the impact of regular peanut consumption for 4 years and demonstrated a sustained protection against the development of peanut allergy even after 12 months of peanut avoidance from 5 to 6 years of age. The PreventADALL trial introduced multiple allergens into babies' diets from early infancy and reduced the prevalence of food allergy at 3 years, especially by protecting against peanut allergy. Immunological studies from the LEAP cohort demonstrated that regular peanut consumption was associated with a prompt induction of peanut-specific IgG4 and reduced manufacture of peanut and Ara h 2-specific IgE. Even after stopping peanut consumption for 5 years, there continued to be a significant fall in peanut-specific Ara h 2 IgE in the consumption group from 5 to 6 years of age (p < .01). Children who developed peanut allergy by 5 years started to develop increasing sensitisation to linear sequential peanut epitopes from 2.5 years of age, suggesting that putative disease-modifying interventions should commence before 3 years. Data comparing clinical outcomes between children undergoing peanut immunotherapy from infancy suggest that younger children can consume higher portions of peanut without reaction on challenge whilst taking immunotherapy, have fewer side effects and are more likely to enjoy remission of PA. Peanut oral immunotherapy modulates T-cell populations in order to bring about hypo-responsiveness of allergy effector cells. Studies are now needed to characterise and compare different states of immunological tolerance. This will accelerate the design of interventions which can promote primary, secondary and tertiary levels of PA prevention across a range of age groups.

Risk subgroups and intervention effects among infants at high risk for peanut allergy: A model for clinical decision making.

The Learning Early About Peanut Allergy (LEAP) trial showed that early dietary introduction of peanut reduced the risk of developing peanut allergy by age 60 months in infants at high risk for peanut allergy. In this secondary analysis of LEAP data, we aimed to determine risk subgroups within these infants and estimate their respective intervention effects of early peanut introduction. LEAP raw data were retrieved from ITNTrialShare.org. Conditional random forest was applied to participants in the peanut avoidance arm to select statistically important features for the classification and regression tree (CART) analysis to group infants based on their risk of peanut allergy at 60 months of age. Intervention effects were estimated for each derived risk subgroup using data from both arms. Our main model was generated based on baseline data when the participants were 4-11 months old. Specific IgE measurements were truncated to account for the limit of detection commonly used by laboratories in clinical practice. The model found infants with higher predicted probability of peanut allergy at 60 months of age had a similar relative risk reduction, but a greater absolute risk reduction in peanut allergy with early introduction of peanut, than those with lower probability. The intervention effects were significant across all risk subgroups. Participants with baseline peanut sIgE ≥0.22 kU/L (n = 78) had an absolute risk reduction of 40.4% (95% CI 27.3, 51.9) whereas participants with baseline peanut sIgE<0.22 kU/L and baseline Ara h 2 sIgE <0.10 kU/L (n = 226) had an absolute risk reduction of 6.5% (95% CI 2.6, 11.0). These findings were consistent in sensitivity analyses using alternative models. In this study, risk subgroups were determined among infants from the LEAP trial based on the probability of developing peanut allergy and the intervention effects of early peanut introduction were estimated. This may be relevant for further risk assessment and personalized clinical decision-making.

Peanut Allergy and Component-Resolved Diagnostics Possibilities-What Are the Benefits?

Peanut allergy is a widespread and potentially life-threatening condition that affects both children and adults, with a growing incidence worldwide. It is estimated to affect around 1-2% of the population in several developed countries. Component-resolved diagnostics is a modern approach to allergy diagnosis that focuses on identifying specific allergenic proteins to provide precise diagnoses and personalized treatment plans. It is a technique that enables the analysis of specific IgE antibodies against tightly defined molecules (components) that constitute the allergen. Component-resolved diagnostics is particularly valuable in peanut allergy diagnosis, helping to determine allergen components associated with severe reactions. It also aids in predicting the course of the allergy and enables the development of personalized immunotherapy plans; however, the full application of it for these purposes still requires more precise studies. In this paper, we present the current knowledge about peanut allergy and component-resolved diagnostics possibilities. We discuss the possibilities of using molecular diagnostics in the diagnosis of peanut allergy. We focus on examining and predicting the development of peanut allergy, including the risk of anaphylaxis, and describe the latest data related to desensitization to peanuts.

Early Peanut Introduction in Infants: Improving Guideline Adherence With EMR Standardization.

Peanut allergy in children is a population health problem. Evidence suggests early peanut introduction (EPI) for infants can reduce the development of peanut allergy. Primary care settings have not widely adopted guidelines recommending EPI. Peanut allergy prevention depends on primary care providers incorporating EPI guidelines into well-child check (WCC) encounters. We aimed to improve guideline adherence in a primary care setting by implementing a bundle of clinical decision support (CDS) tools. Using quality improvement methodology, the team developed a standardized work protocol and CDS tools within an electronic medical record (EMR) at 4, 6, and 9-month WCC encounters. The team executed changes and modifications through plan-do-study-act cycles and analyzed results with statistical process control charts. We collected data from 445 WCC encounters from baseline through sustainability. EMR documentation of EPI guidance at 4, 6, and 9-month WCCs shifted from 13.9% to 83.5% over 12 months. Provider adoption of smart lists and templates increased from 2% to 73%, the distribution of home peanut introduction handouts increased from 5.2% to 54.1%, and caregiver-reported peanut ingestion increased from 0% to 34.6%. Diphtheria-tetanus-acellular pertussis vaccination rates remained at 100% for 6-month visits, and patient in-room time remained at 65 minutes. Quality improvement methodology improved documentation of EPI guidance and increased reported peanut ingestion at routine WCC encounters without impacting other measures. Broader use of bundled CDS tools and EMR standardization could further improve guideline adherence and increase early peanut introduction to prevent peanut allergy in infants.

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.

Longitudinal dynamics of the gut microbiome and metabolome in peanut allergy development

Rising rates of peanut allergy (PA) motivate investigations of its development to inform prevention and therapy. Microbiota and the metabolites they produce shape food allergy risk. We sought to gain insight into gut microbiome and metabolome dynamics in the development of PA. We performed a longitudinal, integrative study of the gut microbiome and metabolome of infants with allergy risk factors but no PA from a multicenter cohort followed through mid-childhood. We performed 16S rRNA sequencing, short chain fatty acid measurements, and global metabolome profiling of fecal samples at infancy and at mid-childhood. In this longitudinal, multicenter sample (n= 122), 28.7% of infants developed PA by mid-childhood (mean age 9 years). Lower infant gut microbiome diversity was associated with PA development (P= .014). Temporal changes in the relative abundance of specific microbiota and gut metabolite levels significantly differed in children who developed PA. PA-bound children had different abundance trajectories of Clostridium sensu stricto 1 sp (false discovery rate (FDR)= 0.015) and Bifidobacterium sp (FDR= 0.033), with butyrate (FDR= 0.045) and isovalerate (FDR= 0.036) decreasing over time. Metabolites associated with PA development clustered within the histidine metabolism pathway. Positive correlations between microbiota, butyrate, and isovalerate and negative correlations with histamine marked the PA-free network. The temporal dynamics of the gut microbiome and metabolome in early childhood are distinct for children who develop PA. These findings inform our thinking on the mechanisms underlying and strategies for potentially preventing PA.

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.

Environmental Exposure to Foods as a Risk Factor for Food Allergy.

Many factors have been reported to contribute to the development of food allergy. Here, we summarize the role of environmental exposure to foods as a major risk factor for developing food allergy. Peanut proteins are detectable and biologically active in household environments, where infants spend a majority of their time, providing an environmental source of allergen exposure. Recent evidence from clinical studies and mouse models suggests both the airway and skin are routes of exposure that lead to peanut sensitization. Environmental exposure to peanut has been clearly associated with the development of peanut allergy, although other factors such as genetic predisposition, microbial exposures, and timing of oral feeding of allergens also likely contribute. Future studies should more comprehensively assess the contributions of each of these factors for a variety of food allergens to provide more clear targets for prevention of food allergy.

Dose and route of administration determine the efficacy of prophylactic immunotherapy for peanut allergy in a Brown Norway rat model.

Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy. Here we compared peanut allergen delivery via the oral, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes for the prevention of peanut allergy in Brown Norway (BN) rats. BN rats were administered PBS or three different doses of peanut protein extract (PPE) via either oral IT (OIT), SLIT, IGIT or SCIT followed by intraperitoneal (IP) injections of PPE to assess the protection from peanut sensitisation. The development of IgE and IgG1 responses to PPE and the major peanut allergens were evaluated by ELISAs. The clinical response to PPE was assessed by an ear swelling test (EST) and proliferation was assessed by stimulating splenocytes with PPE. Low and medium dose OIT (1 and 10 mg) and all doses of SCIT (1, 10, 100 µg) induced sensitisation to PPE, whereas high dose OIT (100 mg), SLIT (10, 100 or 1000 µg) or IGIT (1, 10 and 100 mg) did not. High dose OIT and SLIT as well as high and medium dose IGIT prevented sensitisation from the following IP injections of PPE and suppressed PPE-specific IgE levels in a dose-dependent manner. Hence, administration of peanut protein via different routes confers different risks for sensitisation and protection from peanut allergy development. Overall, the IgE levels toward the individual major peanut allergens followed the PPE-specific IgE levels. Collectively, this study showed that the preventive effect of allergen-specific IT is determined by the interplay between the specific site of PPE delivery for presentation to the immune system, and the allergen quantity, and that targeting and modulating tolerance mechanisms at specific mucosal sites may be a prophylactic strategy for prevention of peanut allergy.

Estimating the Probability of Peanut Allergy Development in the Avoidance Arm of LEAP using Classification and Regression Tree Analysis

The Learning Early About Peanut Allergy (LEAP) trial showed that early dietary introduction of peanut reduced the risk of developing peanut allergy (PA) by age 60 months in children at high risk for PA. The influence of different baseline variables on the probability of developing PA within the peanut avoidance arm are not fully understood.

Suspected gut barrier disruptors and development of food allergy: Adjuvant effects and early immune responses.

Food allergy is an increasing public health challenge worldwide. It has recently been hypothesized that the increase in exposure to intestinal epithelial barrier-damaging biological and chemical agents contribute to this development. In animal models, exposure to adjuvants with a food allergen has been shown to promote sensitization and development of food allergy, and barrier disrupting capacities have been suggested to be one mechanism of adjuvant action. Here, we investigated how gut barrier disrupting compounds affected food allergy development in a mouse model of peanut allergy. Sensitization and clinical peanut allergy in C3H/HEOuJ mice were assessed after repeated oral exposure to peanut extract together with cholera toxin (CT; positive control), the mycotoxin deoxynivalenol (DON), house dust mite (HDM) or the pesticide glyphosate (GLY). In addition, we investigated early effects 4 to 48 h after a single exposure to the compounds by assessing markers of intestinal barrier permeability, alarmin production, intestinal epithelial responses, and local immune responses. CT and DON exerted adjuvant effects on peanut allergy development assessed as clinical anaphylaxis in mice. Early markers were affected only by DON, observed as increased IL-33 (interleukin 33) and thymic stromal lymphopoietin (TSLP) alarmin production in intestines and IL-33 receptor ST2 in serum. DON also induced an inflammatory immune response in lymph node cells stimulated with lipopolysaccharide (LPS). HDM and GLY did not clearly promote clinical food allergy and affected few of the early markers at the doses tested. In conclusion, oral exposure to CT and DON promoted development of clinical anaphylaxis in the peanut allergy mouse model. DON, but not CT, affected the early markers measured in this study, indicating that DON and CT have different modes of action at the early stages of peanut sensitization.

AN EMR INTERVENTION TO IMPROVE EARLY INTRODUCTION OF PEANUTS IN INFANTS AT COMMUNITY-BASED HEALTH CLINICS

<h3>Introduction</h3> Infant peanut introduction is a recommended childhood feeding practice, following the landmark LEAP study showing that early introduction of peanut dramatically reduced rates of peanut allergy in high-risk infants. However, counselling about early introduction at infant well visits may not be happening systematically in all primary care settings. <h3>Methods</h3> In April 2019, we introduced an EMR screening tool in our general pediatrics clinics to discuss peanut allergy risk factors and early peanut introduction at well visits between 4-11 months. A retrospective chart review was undertaken, comparing all infants seen for 4-11 month old well visits in the year following the intervention (April 2019-March 2020) versus the year prior to the intervention (April 2018-March 2019). <h3>Results</h3> A total of 379 charts were screened, 179 pre-intervention and 200 post-intervention. There were no statistically significant differences in baseline characteristics in the pre-intervention and post-intervention groups, including age, sex, and comorbid egg allergy and eczema. Post-intervention, there was a statistically significant increase in discussion of early peanut introduction. 7 infants were screened pre-intervention, while 56 were screened after (p<0.001). There was a statistically significant increase in documentation of peanut in the diet by 12 months, with 5 documented pre-intervention and 23 post-intervention (p=0.001). <h3>Conclusion</h3> While introduction of the EMR screening tool increased discussion of early peanut introduction in community-based clinics, most infants still didn't have documentation of counselling on early peanut introduction in their medical records. Further interventions to improve rates of early peanut introduction are necessary to minimize development of peanut allergy.

Differences in Linear Epitopes of Ara h 9 Recognition in Peanut Allergic and Tolerant, Peach Allergic Patients.

BackgroundPeanut-allergic patients from the Mediterranean region are predominantly sensitized to the lipid transfer protein (LTP) Ara h 9, and the peach LTP Pru p 3 seems to be the primary sensitizer. However, LTP sensitization in peanut allergy is not a predictive marker for clinically relevant symptoms.ObjectiveWe aimed to identify sequential epitopes of IgE and IgG4 from Pru p 3 and Ara h 9 in peach-allergic patients sensitized to peanuts. We also sought to determine the differences in IgE and IgG4 binding between patients who had developed peanut allergy and those tolerating peanuts.MethodsA total of 46 peach-allergic patients sensitized to peanuts were selected. A total of 35 patients were allergic to peanuts (peanut-allergic group) and 11 were tolerant to peanuts (peanut-tolerant group). We measured sIgE and sIgG4 in peanut, peach, and their recombinant allergen (Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) with fluorescence enzyme immunoassay. We examined the IgE and IgG4 binding to sequential epitopes using a peptide microarray corresponding to linear sequences of the LTPs Ara h 9 and Pru p 3 with a library of overlapping peptides with a length of 20 amino acids (aa) and an offset of 3 aa.ResultsThe frequency and the intensity of IgE recognition of Ara h 9 and Pru p 3 peptides were higher in the peanut-tolerant group than in the peanut-allergic group. We found four Ara h 9 peptides (p4, p14, p21, and p25) and four Pru p 3 peptides (p1, p3, p21, and p24) with a significantly elevated IgE recognition in peanut-tolerant patients. Only one peptide of Ara h 9 (p4) recognized by IgG4 was significantly elevated in the peanut-tolerant group. The IgG4/IgE ratio of Ara h 9 peptide 4 was significantly higher in peanut-tolerant patients than in peanut-allergic patients, while no significant differences were observed in the IgG4/IgE ratio of this peptide in Pru p 3.ConclusionAlthough we found significant differences in IgE and IgG4 recognition of Ara h 9 and Pru p 3 between peanut-tolerant and peanut-allergic patients (all of whom were allergic to peach), polyclonal IgE peptide recognition of both LTPs was observed in peach-allergic patients tolerating peanuts. However, the IgG4 blocking antibodies against Ara h 9 peptide 4 could provide an explanation for the absence of clinical reactivity in peanut-tolerant peach-allergic patients. Further studies are needed to validate the usefulness of IgG4 antibodies against Ara h 9 peptide 4 for peanut allergy diagnosis.

The Case for Prompt Salvage Infant Peanut Oral Immunotherapy Following Failed Primary Prevention

Recent guideline recommendations have shifted from recommending prolonged avoidance of allergenic foods in the first 3 years of life to a primary prevention approach involving the deliberate early introduction to infants at risk of developing food allergy. Despite this, some infants, especially those with severe eczema who are at highest risk for developing peanut allergy, fail to receive the preventative benefits of early peanut introduction due to hesitancy and other factors. Difficulty adhering to regular ingestion after introduction further reduces the effectiveness of primary prevention. As emerging real-world evidence has demonstrated that performing peanut oral immunotherapy (OIT) among infants is effective and safe, peanut OIT could be a treatment option for infants with peanut allergy. This review discusses the benefits, risks, and barriers to offering peanut OIT to infants who fail primary prevention strategies. We propose the novel concept that infants with peanut allergy be offered peanut OIT as soon as possible after failed peanut introduction through a shared decision-making process with the family, where there is a preference for active management rather than avoidance.

A mouse model of the LEAP study reveals a role for CTLA-4 in preventing peanut allergy induced by environmental peanut exposure

A human study, Learning Early About Peanut Allergy (LEAP), showed that early introduction of peanut products decreases the prevalence of peanut allergy among children. However, the immunologic mechanisms mediating the protective effects of consuming peanut products are not well understood. The objective was to develop a mouse model that simulates the LEAP study and investigate the underlying mechanisms for the study observations. Adult naive BALB/c mice were fed a commercial peanut butter product (Skippy) or buffer control and concomitantly exposed to peanut flour through the airway or skin to mimic environmental exposure. The animals were analyzed for anaphylactic reaction and by molecular and immunologic approaches. After exposure to peanut flour through the airway or skin, naive mice developed peanut allergy, as demonstrated by acute and systemic anaphylaxis in response to challenge with peanut extract. Ingestion of Skippy, however, nearly abolished the increase in peanut-specific IgE and IgG and protected animals from developing anaphylaxis. Skippy-fed mice showed reduced numbers of T follicular helper (Tfh) cells and germinal center B cells in their draining lymph nodes, and single-cell RNA sequencing revealed a CD4+ T-cell population expressing cytotoxic T lymphocyte-associated protein 4 (CTLA-4) in these animals. Critically, blocking CTLA-4 with antibody increased levels of peanut-specific antibodies and reversed the protective effects of Skippy. Ingestion of a peanut product protects mice from peanut allergy induced by environmental exposure to peanuts, and the CTLA-4 pathway, which regulates Tfh cell responses, likely plays a pivotal role in this protection.

Current Peanut Introduction Practices amongst a Large, Representative Sample of US Households

The NIAID-sponsored guidelines recommending early peanut introduction amongst infants at high risk for developing peanut allergy in 2017. Assessing guideline awareness and peanut introduction practices amongst a national cohort of caregivers has not since been evaluated.

The kinetics of peanut allergy development and resolution in the EAT, LEAP, and PAS cohorts

Previous studies report up to 20% of peanut allergy (PA) resolves by adolescence. Immunological phenotypes associated with PA persistence and resolution are not well described.