Peanut Allergy Study Research Articles

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response. Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge. Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p< 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg). Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

Defining the window of opportunity and target populations to prevent peanut allergy

Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants. We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population. Data from the Enquiring About Tolerance (EAT; n=1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n=640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n= 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result. Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%. The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants' diet at 4 to 6 months of life.

Evaluating the predictive utility of patient‐oriented scoring of atopic dermatitis (PO‐SCORAD) versus Patient‐Oriented Eczema Measure (POEM) for peanut sensitivity in patients with atopic dermatitis

AbstractBackgroundCurrent Guidelines from the National Institute of Allergy and Infectious Disease (NIAID) are based on the Learning Early About Peanut Allergy Study (LEAP Study) results and recommend early introduction of peanuts to children with atopic dermatitis (AD) depending on their disease severity. There is yet to be a widely accepted method of evaluating AD severity among clinicians. Thus, the purpose of this study was to determine the association between AD severity as measured by patient‐oriented scoring of atopic dermatitis(PO‐SCORAD) and Patient Oriented Eczema Measure (POEM) surveys and peanut sensitivity as measured by Immunoglobulin E (IgE) or skin prick test levels.ObjectivesThe primary objective of this study was to determine the association between AD severity as measured by PO‐SCORAD and POEM surveys and peanut sensitivity as measured by IgE or skin prick test levels. The secondary objective of this study was to determine the rate of peanut sensitisation amongst patients with ‘mild AD’ as defined by PO‐SCORAD score of 1−27 and a POEM score of 0‐7.MethodsPatients between 3 months and 18 years old undergoing IgE or skin prick testing for peanut allergy were recruited from two allergy clinics in the Chicagoland area. Patients or their guardians completed a PO‐SCORAD survey and POEM survey.ResultsThere was no significant difference in AD severity (as measured by PO‐SCORAD or POEM score) between sexes or age groups (&lt;12 months vs. ≥12 months). Moreover, there was no significant relationship found between PO‐SCORAD or POEM scores and rate of peanut sensitivity.ConclusionDespite no significant relationship found between PO‐SCORAD or POEM score and peanut sensitivity, the hypothesis that AD severity can predict risk of peanut sensitivity may still be valid based on a growing body of evidence. The negative results of this study are likely due to the small study population used due to limitations of the COVID‐19 pandemic. Moreover, evaluating AD severity through PO‐SCORAD and POEM surveys may not be ideal for paediatric patients.

Relevance of Early Introduction of Cow's Milk Proteins for Prevention of Cow's Milk Allergy.

Food allergy incidence has increased worldwide over the last 20 years. For prevention of food allergy, current guidelines do not recommend delaying the introduction of allergenic foods. Several groundbreaking studies, such as the Learning Early About Peanut Allergy study, showed that the relatively early introduction of this allergenic food between 4–6 months of age reduces the risk of peanut allergy. However, less is known about the introduction of cow’s milk, as many children already receive cow’s-milk-based formula much earlier in life. This can be regular cow’s milk formula with intact milk proteins or hydrolyzed formulas. Several recent studies have investigated the effects of early introduction of cow’s-milk-based formulas with intact milk proteins on the development of cow’s milk allergy while breastfeeding. These studies suggest that depending on the time of introduction and the duration of administration of cow’s milk, the risk of cow’s milk allergy can be reduced (early introduction) or increased (very early introduction followed by discontinuation). The aim of this narrative review is to summarize these studies and to discuss the impact of early introduction of intact cow’s milk protein—as well as hydrolyzed milk protein formulas—and the development of tolerance versus allergy towards cow’s milk proteins.

Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations

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. However, the immunologic mechanism of this strain's susceptibility is not known. 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 because both genes have been associated with food allergy. We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them 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. In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after 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 compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.

Reduced Risk of Peanut Sensitization Following Exposure Through Breastfeeding and Early Peanut Introduction

To evaluate the relationship between maternal consumption of peanut while breastfeeding, the timing of direct oral peanut introduction, and sensitization to peanut at 7 years of age.The study included 342 children from the Canadian Childhood Asthma Primary Prevention Study who had a family history of asthma or immunoglobulin E–mediated allergic disease.A secondary analysis of the Canadian Childhood Asthma Primary Prevention Study cohort was performed. Pregnant women were recruited and randomly assigned to a multifaceted intervention group or a control group. The control group received no specific maternal or infant diet instructions. Mothers in the intervention group were asked to do the following: (1) avoid peanuts, nuts, fish, and eggs during pregnancy and while breastfeeding; (2) breastfeed for 4 to 12 months; (3) avoid introducing solid foods to infants until after 6 months of age; and (4) delay the introduction of allergenic foods until at least 12 months of age. Maternal and infant diet questionnaires were completed at 2 weeks and 4, 8, 12, 18, and 24 months of age. At 7 years of age, children had skin prick testing to peanut performed.Of 342 children, 32 (9.4%) were sensitized to peanut by 7 years of age, with no significant difference seen between study groups. The lowest incidence of peanut sensitization (1.7%) was found when mothers consumed peanut while breastfeeding and infants were introduced to peanuts in their diet before 12 months of age; an interaction analysis was used to confirm that this combination was protective. Isolated exposure to maternal peanut consumption while breastfeeding or infant peanut introduction before 12 months of age was associated with an increased risk of peanut sensitization (adjusted odds ratio 12.45 [95% confidence interval 1.18–131.30] and adjusted odds ratio 8.30 [95% confidence interval 1.05–65.80], respectively).We found that peanut introduction before 12 months of age combined with maternal peanut consumption while breastfeeding was associated with the lowest risk of peanut sensitization by 7 years of age compared with maternal or infant peanut consumption in isolation.The Learning Early About Peanut Allergy study revealed that in high-risk infants, early peanut introduction reduced the risk of peanut allergy. The impact of maternal peanut consumption during pregnancy or while breastfeeding remains unclear. This study revealed that the group with maternal peanut consumption while breastfeeding, combined with early peanut introduction to the infant, yielded a reduced risk of peanut sensitization at 7 years of age. However, researchers also found that early peanut consumption alone led to a marked increase in peanut sensitization, which would appear contradictory to the Learning Early About Peanut Allergy study. This study has several limitations, including sample size, incomplete and limited dietary information, and a lack of oral food challenges used to diagnose peanut allergy. Furthermore, research is clearly needed before suggesting any changes to our current recommendations.

A Synopsis of the Synopses, 2017-2018.

The authors of this Synopsis Book report on a spectrum of advances and observations that will provide greater insight and clinical use, impacting the care of children with allergic and immunologic diseases now and in the near future. Reviewers have selected impactful articles that will help advance patient care through improved diagnosis and management and raise awareness of the upcoming treatments that will enhance our ability to deliver precision medicine. The increase in prevalence of allergic disorders and asthma continues to be concerning; thus, a number of studies reviewed here are focused on identifying risk factors to inform prevention strategies. Several studies selected by reviewers add to the literature, demonstrating an association between the microbiome and allergic sensitization and clinical allergy. However, the authors of other studies demonstrate that the current level of evidence to support the use of prebiotics and probiotics for allergy prevention is low. The opportunity for early dietary intervention in reducing the risk of allergy was demonstrated by the Learning Early About Peanut allergy study and guidelines support the early introduction of peanut for allergy prevention in children at risk.1 In some studies selected by reviewers, the potential for other dietary modifications …

Allergen Specificity of Early Peanut Consumption and Effect on Development of Allergic Disease in the Learning Early About Peanut Allergy Study Cohort

G du Toit, PH Sayre, G Roberts; Immune Tolerance Network Learning Early About Peanut Allergy study team. J Allergy Clin Immunol. 2018;141(4):1343–1353 In this a priori study, the aim is to evaluate the effect of early dietary peanut exposure on the development or resolution of coexistent food allergies and atopic diseases in the Learning Early About Peanut Allergy (LEAP) and LEAP-On cohorts. Infants between 4 months and 11 months of age with severe eczema and/or egg allergy were included in the study. In the LEAP study, subjects were divided into 2 separate study populations on the basis of peanut skin prick test and then randomly assigned to peanut avoidance or consumption of 6 g of peanut protein …

Allergen specificity of early peanut consumption and effect on development of allergic disease in the Learning Early About Peanut Allergy study cohort

Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5years of age in the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific. We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization. Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement. A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption. Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.

Infant and Young Child Peanut Challenges, a Clinical Application of the Learning Early About Peanut Allergy Study

Infant and Young Child Peanut Challenges, a Clinical Application of the Learning Early About Peanut Allergy Study

The National Institutes of Allergy and Infectious Diseases sponsored guidelines on preventing peanut allergy: A new paradigm in food allergy prevention.

Peanut allergy is a significant public health problem without proven treatment or cure at present. In 2000, the American Academy of Pediatrics recommended that solid-food introduction be delayed in infants at high risk, including peanut introduction, until age 3 years. In 2008, the American Academy of Pediatrics revised these recommendations based on limited evidence of benefit and, instead, recommended solid-food introduction not be delayed past 4-6 months of life. In 2015, the Learning Early About Peanut Allergy study showed that early peanut introduction (between 4 and 11 months of life) was associated with a significant absolute and relative risk reduction in the development of peanut allergy compared with delayed introduction. Based on these findings, the National Institutes of Allergy and Infectious Diseases sponsored an expert panel to create an addendum to the 2010 Food Allergy Guidelines that specifically focuses on peanut allergy prevention. The addendum recommends that children with severe eczema, egg allergy, or both have peanut introduced as early as 4-6 months of life, after assessment by a trained allergy specialist. For children with mild-to-moderate eczema, peanut can be introduced at ∼6 months, without the need for specialist evaluation. For children with no eczema, peanut can be introduced in accordance with family and cultural preferences, without the need for specialist evaluation. Adherence to these clinical practice recommendations can help potentially reduce the number of cases of peanut allergy per year. However, this can only be accomplished with the cooperation of parents and health care providers who adhere to these recommendations.

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

Peanut allergenicity

To provide the reader with a relevant review of the structure and allergenicity of the major peanut allergens, while also exploring predictors of clinical reactivity to peanuts, the natural history of peanut allergy, and novel therapeutic strategies for peanut hypersensitivity. A PubMed search for the years 1980 to 2004 was performed using the following search terms: peanut allergy, food allergy, anaphylaxis, peanut allergen structure, and peanut immunotherapy. Articles highlighting major advances in the study of peanut allergy were selected for further review. Peanut allergy is the most serious of the hypersensitivity reactions to foods due to its persistence and high risk of severe anaphylaxis. The major peanut allergens and their associated immunodominant IgE-binding epitopes have been characterized. Definition of these allergens has lead to an increased understanding of the peanut-specific immunologic response and improved predictors of clinical reactivity to peanuts. An understanding of these mechanisms is vital for the eventual development of safe and effective immunotherapy for peanut allergic patients. Novel therapeutic and diagnostic approaches are being developed for patients with peanut hypersensitivity. Improved understanding of the molecular structure of the major peanut allergens and the peanut-specific immune response has lead to significant diagnostic and therapeutic advances in the study of peanut allergy.