Development Of Peanut Allergy Research Articles

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.

Racial and Ethnic Differences in Infant Peanut Introduction Beliefs and Practices Among Parents/Caregivers in the United States

Early introduction of peanut reduces the frequency of peanut allergy development among children. However, timing of peanut introduction among infants may vary by race. This study aims to explore potential racial and ethnic differences in infant peanut introduction practices amongst US parents/caregivers.

P109 IMPROVING IMPLEMENTATION OF EARLY PEANUT INTRODUCTION GUIDELINES AMONG PEDIATRIC HOUSE STAFF IN AN INNER-CITY HOSPITAL

The 2015 Learning Early About Peanut Allergy (LEAP) landmark study led to the 2017 Addendum Guidelines, which recommend early peanut introduction to infants at increased risk of developing peanut allergy. Educating pediatric house staff and attendings will result in increased knowledge of these guidelines and eventually lead to reduced development of peanut allergy.

White paper on peanut allergy- part1: Epidemiology, burden of disease, health economic aspects.

Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis.The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4–2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy.Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction.This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.

Human monocyte-derived type 1 and 2 macrophages recognize Ara h 1, a major peanut allergen, by different mechanisms

Evidence has suggested that major peanut allergen Ara h 1 activates dendritic cells (DCs) via interaction with DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin), a C-type lectin receptor, and contributes to development of peanut allergy. Since macrophages, as well as DCs, play a crucial role in innate immunity, we investigated whether natural Ara h 1 (nAra h 1) activates two different subsets of macrophages, human monocyte derived macrophage type 1 (hMDM1: pro-inflammatory model) and type 2 (hMDM2: anti-inflammatory model). hMDM1 and hMDM2 predominantly produced pro-inflammatory cytokines (IL-6 and TNF-α) and an anti-inflammatory cytokine (IL-10) in response to nAra h 1, respectively. hMDM2 took up nAra h 1 and expressed DC-SIGN at higher levels than hMDM1. However, small interfering RNA knockdown of DC-SIGN did not suppress nAra h 1 uptake and nAra h 1-mediated cytokine production in hMDM2. Inhibitors of scavenger receptor class A type I (SR-AI) suppressed the response of hMDM2, but not of hMDM1, suggesting that SR-AI is a major receptor in hMDM2 for nAra h 1 recognition and internalization. nAra h 1 appears to exert stimulatory capacity on DC and macrophages via different receptors. This study advances our understanding how a major peanut allergen interacts with innate immunity.

PD-1 regulates affinity maturation of allergen-specific antibodies and severity of peanut allergy in mice

Abstract Programmed cell death-1 (PD-1), a member of the CD28 family, is critical for regulation of immune cell activation and maintenance of peripheral tolerance. Blocking antibodies against PD-1 have been used to sustain activation of T cells in cancer immunotherapy. T follicular helper (Tfh) cells play important role in the differentiation and maturation of antigen-specific B cells. Tfh cells highly and constitutively express PD-1; however, our knowledge is limited regarding the role of PD-1 in Tfh cell function and antibody response. We addressed this question by using a Tfh-dependent mouse model of peanut allergy. When naïve BALB/c mice were exposed to peanut flour by inhalation for 4 weeks, they developed peanut allergy as demonstrated by increased plasma levels of peanut-specific IgE and IgG antibodies and manifestation of acute anaphylaxis upon challenge with peanut extract. To examine the roles of PD-1, we administered a PD-1 blocking antibody to the animals during their exposure to peanut flour. Mice administered anti-PD-1 did not develop anaphylaxis even when they were challenged with peanut extract. Anti-PD1 treatment increased the number of Tfh cells and germinal center B cells in draining lymph nodes, and it increased plasma levels of peanut-specific IgG antibodies. Importantly, PD-1 blockade promoted the accumulation of low-affinity antibodies while it maintained the levels of high-affinity antibodies. These findings suggest that quality of allergen-specific antibodies affects the severity of allergic immune responses. Understanding the mechanisms that explain how PD-1 regulates the Tfh-B interaction and affinity maturation of antibodies likely leads to a better understanding of pathophysiology of allergic diseases.

Food protein-induced enterocolitis syndrome to nuts: An increasing phenomenon

Food protein-induced enterocolitis syndrome (FPIES) is a non–immunoglobulin E (IgE)-mediated food allergy which typically presents in infancy. Although rice is a rare cause of IgE-mediated food allergy, it is one of the most common triggers of FPIES in Australia and the United States. 1 Mehr S. Frith K. Barnes E.H. Campbell D.E. FPIES Study GroupFood protein-induced enterocolitis syndrome in Australia: a population-based study, 2012-2014. J Allergy Clin Immunol. 2017; 140: 1323-1330 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ,2 Ruffner M.A. Ruyman K. Bami S. Cianferoni A. Brown-Whitehorn T. Spergel J.M. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract. 2013; 1: 343-349 Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Conversely, peanut and tree nuts are rarely described to cause FPIES, but are common triggers of IgE-mediated food reactions. Ruffner et al 2 Ruffner M.A. Ruyman K. Bami S. Cianferoni A. Brown-Whitehorn T. Spergel J.M. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract. 2013; 1: 343-349 Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar reported peanut and tree nut FPIES in only 2% and less than 1% of children, respectively, in a retrospective cohort of 462 children from a single institution. Mehr et al 1 Mehr S. Frith K. Barnes E.H. Campbell D.E. FPIES Study GroupFood protein-induced enterocolitis syndrome in Australia: a population-based study, 2012-2014. J Allergy Clin Immunol. 2017; 140: 1323-1330 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar reported a single case (0.5%) of peanut FPIES in a prospective population-based study of 230 children. Case reports of peanut FPIES have been published, 3 Mansi J. Anvari S. Anagnostou A. Development of peanut allergy despite early introduction: a real-world case series in the United States. Pediatr Allergy Immunol. 2020; 31: 589-592 Crossref PubMed Scopus (2) Google Scholar , 4 Robbins K.A. Ackermann O.R. Carter C.A. Uygungil B. Sprunger A. Sharma H.P. Food protein-induced enterocolitis syndrome to peanut with early introduction: a clinical dilemma. J Allergy Clin Immunol Pract. 2018; 6: 664-666 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar and 1 case of peanut FPIES was noted as a reason for discontinuation in the Learning Early About Peanut (LEAP) allergy trial. 5 Du Toit G. Roberts G. Sayre P.H. et al. Randomised trial of peanut consumption in infants at rick of peanut allergy. N Engl J Med. 2015; 372: 803-813 Crossref PubMed Scopus (1129) Google Scholar We recently noted an increase in the number of children being referred with peanut FPIES to our private allergy services, in Melbourne, Australia.

Evolution of epitope-specific IgE and IgG4 antibodies in children enrolled in the LEAP trial

In the LEAP (Learning Early About Peanut Allergy) trial, early consumption of peanut in high-risk infants was found to decrease the rate of peanut allergy at 5 years of age. Sequential epitope-specific (ses-)IgE is a promising biomarker of clinical peanut reactivity. We sought to compare the evolution of ses-IgE and ses-IgG4 in children who developed (or not) peanut allergy and to evaluate the immunomodulatory effects of early peanut consumption on these antibodies. Sera from 341 children (LEAP cohort) were assayed at baseline, 1, 2.5, and 5 years of age, with allergy status determined by oral food challenge at 5 years. Abead-based epitope assay was used to quantitate ses-IgE and ses-IgG4 to 64 sequential epitopes from Ara h 1 to Ara h 3 and was analyzed using linear mixed-effect models. In children avoiding peanut who became peanut allergic, the bulk of peanut ses-IgE did not develop until after 2.5 years. Minimal increases of ses-IgE occurred after 1 year in consumers, but not to the same epitopes as those in children developing peanut allergy. No major changes in ses-IgE were seen in nonallergic or sensitized children. IgE in sensitized consumers was detected against peanut proteins. ses-IgG4 increased over time in most children regardless of consumption or allergy status. Early peanut consumption in infants at high risk of developing peanut allergy appears to divert the immunologic response to a presumably "protective" effect. In general, consumers tend to generate ses-IgG4 earlier and in greater quantities than nonconsumers do, whereas only avoiders tend to generate significant quantities of ses-IgE.

Assessment of Early Peanut Introduction Guidelines Among Pediatricians In An Inner-city Hospital

Peanuts are the leading cause of death from food-induced anaphylaxis. The 2015 Learning Early About Peanut Allergy (LEAP) landmark study led to the 2017 Addendum Guidelines, which recommends early peanut introduction to infants at increased risk of developing peanut allergy. It is unclear to what extend general pediatricians follow these guidelines. Educating pediatric residents and attendings will result in an increased knowledge of these evidence-based early peanut introduction guidelines, leading to reduced development of peanut allergy in the pediatric population.

Clinical Factors Associated With Peanut Allergy in a High-Risk Infant Cohort

SH Sicherer, RA Wood, TT Perry. Allergy . 2019;74(11):2199–2211 This study examined factors associated with the development of peanut allergy in high risk infants. The study included 511 infants aged 3–15 months from the prospective, observational Consortium for Food Allergy Research (CoFAR2) study, who were at high risk of peanut allergy because of moderate-to-severe atopic dermatitis (39.5%), egg or milk allergy (17.8%) or both (42.7%). Infants with known peanut allergy or peanut-specific IgE >5 kU/L at the time of enrollment were excluded. Participants were assessed for peanut allergy at enrollment, 6 months, 12 months, and annually …

An update on international practice variation in peanut introduction: conundrums, controversies, and a new direction.

Introduction of peanut during the first year of life is associated with an 81% relative risk reduction of developing peanut allergy in infants with severe eczema, egg allergy, or both. However, significant international variation exists in risk stratification prior to peanut introduction. A policy-level screening approach, such as the one in the United States, is not practical and is associated with higher costs and more cases of peanut allergy over time, in contrast to international models that recommend universal early introduction without prescreening. In Australia, population-level efforts to introduce peanut early without screening have demonstrated high rates of peanut introduction before 12 months of age and low rates of severe allergic reactions. In contrast, screening prior to peanut introduction in the United States is associated with 'screening creep' - the tendency of clinicians to test populations where screening is not recommended. Early peanut introduction can reduce the risk of developing food allergy and is more effective without a risk-based screening approach. In some circumstances, shared clinical decision-making can facilitate food allergy prevention in a manner consistent with family values and preferences.

Peanut consumption habits and incidence of new peanut allergy in a cohort of younger siblings of peanut-allergic children

This decade has seen major changes in food allergy primary prevention. The Learning Early About Peanut allergy (LEAP) and LEAP-on trials showed that early peanut introduction (4-11 months) is associated with a decreased risk of developing peanut allergy in high-risk children. Early peanut introduction is now recommended in recent guidelines for high-risk children including younger siblings of peanut-allergic children.1-3

Timing of exposure to environmental adjuvants is critical to mitigate peanut allergy

Toll-like receptor ligands in indoor dust act as environmental adjuvants to promote sensitization to inhaled peanut in mice. The timing of exposure to environmental adjuvants relative to peanut is a determinant of peanut allergy development.

Food allergy prevention, including early food introduction.

As the prevalence of immunoglobulin E (IgE)-mediated food allergy continues to increase without an imminent cure, prevention has become an urgent need. A breakthrough study that shows that early consumption of peanut can prevent the development of peanut allergy has led for a push in early interventions. Theories associated with the increasing prevalence of food allergy lend themselves to areas of potential intervention, e.g., age at time of food introduction, infant feeding practices, microbiome influences, diet composition, vitamin D deficiency, and increasing rates of eczema. This review focused on the available data from studies that investigated early interventions to decrease the risk of food allergy.

Assessment of Pediatrician Awareness and Implementation of the Addendum Guidelines for the Prevention of Peanut Allergy in the United States

The 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States recommend that pediatricians assess infant peanut allergy risk and introduce peanut in the diet at age 4 to 6 months. Early introduction has the potential to prevent peanut allergy development. To measure the rates of guideline awareness and implementation and to identify barriers to and factors associated with implementation among US pediatricians. This population-based study survey used a 29-item electronic survey instrument that was administered to pediatricians practicing across the United States from June 1, 2018, to December 1, 2018. Invitations to complete a survey were emailed to all pediatricians in the American Academy of Pediatrics vendor database. Eligible participants were nonretired US-based pediatricians providing general care to infants aged 12 months or younger. The primary outcome was the prevalence of guideline implementation, which was measured by 1 survey item about awareness followed by a second item about implementation. Secondary outcomes included identification of guidelines-focused services provided by pediatricians, knowledge of the guidelines (measured with 3 clinical scenarios), barriers to guideline implementation, need for training, and facilitators of guideline implementation. A total of 1781 pediatricians were eligible to participate and completed the entire survey. Most respondents self-identified as white (1287 [72.5%]) and female (1210 [67.4%]) individuals. Overall, 1725 (93.4%; 95% CI, 92.2%-94.5%) pediatricians reported being aware of the guidelines. Of those pediatricians who had knowledge of the guidelines, 497 (28.9%; 95% CI, 26.8%-31.1%) reported full implementation and 1105 (64.3%; 95% CI, 62.0%-66.6%) reported partial implementation. Common barriers to implementation included parental concerns about allergic reactions (reported by 575 respondents [36.6%; 95% CI, 34.3%-39.1%]), uncertainty in understanding and correctly applying the guidelines (reported by 521 respondents [33.2%; 95% CI, 30.9%-35.6%]), and conducting in-office supervised feedings (reported by 509 respondents [32.4%; 95% CI, 30.1%-34.8%]). Many pediatricians (1175 [68.4%; 95% CI, 66.1%-70.5%]) reported a need for further training on the guidelines. This survey found that most pediatrician respondents appeared to know of the 2017 guidelines, but less than one-third of respondents reported full implementation. Results of this study may inform future efforts to eliminate barriers to guideline implementation and adherence, thereby reducing the incidence of peanut allergy in infants.

Virtually supported home peanut introduction during COVID-19 for at-risk infants

Virtually supported home peanut introduction during COVID-19 for at-risk infants

Peanut Allergy: New Advances and Ongoing Controversies.

Peanut allergy is one of the most common food allergies in children, with increasing prevalence over time. The dual-allergen exposure hypothesis now supports transcutaneous sensitization to peanut as a likely pathophysiologic mechanism for peanut allergy development. As a result, there is emerging evidence that early peanut introduction has a role in peanut allergy prevention. Current first-line diagnostic tests for peanut allergy have limited specificity, which may be enhanced with emerging tools such as component-resolved diagnostics. Although management of peanut allergy includes avoidance and carrying an epinephrine autoinjector, risk of fatal anaphylaxis is extremely low, and there is minimal risk related to cutaneous or inhalational exposure. Quality of life in children with peanut allergy requires significant focus. Moving forward, oral and epicutaneous immunotherapy are emerging and exciting tools that may have a role to play in desensitization to peanut.

Factors Associated with Frequency of Peanut Consumption in Korea: A National Population-Based Study.

Household peanut exposure via skin in infants with impaired skin barrier function is a risk factor for peanut allergy development. The aim of this study is to investigate the peanut consumption of Koreans using national representative data. We used data from the Korean National Health and Nutrition Examination Survey 2012–2016, consisting of data from 17,625 adults who complete the survey. Peanut intake was assessed using a 24-h recall method. Of the study population, 10,552 (59.9%), 6726 (38.2%), and 347 (1.9%) subjects were categorized into non-intake, intermittent intake, and frequent intake group, respectively. Ordered logistic regression models were used to examine the association between sociodemographic and dietary factors and the frequency of peanut intake. After adjusting for confounders, increasing age (adjusted odds ratio (aOR) 1.03; 95% confidence interval (CI) 1.03–1.04), higher education (high school graduates: aOR 1.75, 95 CI 1.39–2.19; higher than college: aOR 2.11, 95% CI 1.65–2.70), and prudent dietary scores in the second (aOR 1.71; 95% CI 1.47–1.99), third (aOR 2.53; 95% CI 2.16–2.97) and the fourth quartiles (aOR 3.72; 95%CI 3.16–4.40) were associated with a high frequency of peanut consumption. This information may be helpful not only in public health research for nutrition but also in personal management for the prevention of peanut allergy in Korea.

Development of peanut allergy is associated with coding SNPs in the C-terminus of the IL-33 receptor that impact signaling and TH2 effector function

Development of peanut allergy is associated with coding SNPs in the C-terminus of the IL-33 receptor that impact signaling and TH2 effector function

Unmet needs of children with peanut allergy: Aligning the risks and the evidence

BackgroundPeanut allergy is a potentially severe and lifelong allergy, with few effective treatments or preventive measures. ObjectiveTo convene an expert panel of allergists, pediatricians, and advocates to discuss and highlight unmet needs in the prevention and management of peanut allergies. MethodsLiterature searches of PubMed were performed. The panel evaluated published data on the prevention of peanut allergy, treatment of existing peanut allergy, and management of reactions after unintentional peanut exposures. ResultsThe following key unmet needs in the prevention and management of peanut allergy were identified: (1) enhancing and optimizing implementation of early peanut introduction as a means of preventing the development of peanut allergy, (2) developing knowledge translation strategies regarding the safety and efficacy data for current and emerging immunotherapies for peanut-allergic children to support their use in clinical practice, and (3) promoting understanding of true exposure risk in allergic individuals and ensuring access to epinephrine for unintentional exposures that provoke severe reactions. Practitioners should help educate caregivers about the actual risks associated with peanut allergy and its prevention and management so that treatment decisions can be evidence based rather than fear based. Support tools are needed to help address caregiver goals, expectations, and psychological barriers, as well as identify facilitators for prevention and treatment strategies. ConclusionThere are significant unmet needs in our understanding of peanut allergy; addressing these needs will help to enhance understanding of how to most effectively prevent and treat peanut allergy, as well as educate the food-allergic and nonallergic community regarding current evidence-based practices.