Peanut-specific Immunoglobulin E Research Articles

CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy.

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23+IgG1+ memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23+IgG1+ memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of "type 2-marked" IgG1+ memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)- and IL-13-regulated genes, such as FCER2/CD23+, IL4R, and germline IGHE, and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of "type 2-marked" IgG1+ memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23+IgG1+ memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy.

High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy

SummaryPeanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies. We observe a striking diversification and boosting of the peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE levels against individual epitopes. High-resolution epitope mapping reveals shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. Individual differences in epitope recognition identified via AllerScan could inform safer and more effective personalized immunotherapy.

Real–World Experience With Peanut Oral Immunotherapy: Lessons Learned From 270 Patients

This retrospective record review reports observations on the treatment of 270 patients with peanut allergy with peanut oral immunotherapy (POIT).The study included 270 patients between the ages of 4 and 18 years who received POIT in a single practice between 2009 and 2017. A total of 96.7% of patients had a history of an immunoglobulin E–mediated reaction, 70.7% had experienced anaphylaxis, 26% had a peanut-specific immunoglobulin E (PSIgE) concentration of >100 kU/mL, and 9.6% had a positive peanut challenge result within 2 years of inception of POIT. No patient was excluded on the basis of severity of previous reaction(s) or PSIgE concentration. Patients with a history of eosinophilic esophagitis or gastroenteritis were excluded.The treatment protocol began with 2.5 µg of peanut protein. Dose increases were administered under direct observation. Patients reached a target dose of 3000 mg of peanut protein, underwent a 6000-mg challenge, and then began a 2000-mg maintenance dose administered at home 1 to 2 times per day for a minimum of 3 years. The treatment team made dose adjustments and decisions regarding discontinuation of therapy on the basis of collaborative clinical judgment. Patients and caregivers were instructed to report any adverse reactions more significant than transient, self-limited oral pruritis or abdominal discomfort.A total of 214 of 270 patients (79%) completed POIT dose escalation. Age (P < .001) and PSIgE (P < .001) correlated inversely with completion of dose escalation. For each year increase in patient age after 5, there was a 17% decrease in the odds ratio of reaching the escalation target (P < .001). One hundred epinephrine-treated reactions occurred in 63 patients (23%) during escalation. Intermittent asthma and higher PSIgE levels increased the risk of epinephrine-treated reactions (P = .035 and .019, respectively). Eosinophilic esophagitis–like oral immunotherapy–related syndrome occurred in 37 patients (13.7%). Intermittent asthma and higher PSIgE levels increased the risk of eosinophilic esophagitis–like oral immunotherapy–related syndrome (P = .014 and <.001, respectively). After 3 years of maintenance treatment, 14 patients were able to achieve sustained peanut unresponsiveness, defined as tolerance of 6000 mg of peanut protein after avoiding peanut for 30 days. The best predictors of sustained unresponsiveness were a pretreatment PSIgE level <20 kU/L and a prechallenge PSIgE level <1 kU/L.In an allergy office practice, 79% of patients were able to complete a POIT desensitization protocol and maintain a desensitized state with daily peanut dosing.This study demonstrates that patients can achieve successful peanut desensitization despite a history of previous reaction(s) or markedly elevated PSIgE levels. Epinephrine-treated reactions did occur during POIT, demonstrating that risk of significant allergic reactions was not eliminated. Reduced likelihood of achieving the target dose with increasing age makes early intervention attractive. Additional future studies are necessary to improve risk assessment and identification of patients likely to achieve sustained unresponsiveness.

Peanut protein-polyphenol aggregate complexation suppresses allergic sensitization to peanut by reducing peanut-specific IgE in C3H/HeJ mice

Peanut allergy is usually lifelong and accidental exposure impose formidable risk. The aim of this study was to assess the capacity of peanut proteins complexed to polyphenol extracts to reduce allergic response in C3H/HeJ mice. Mice were sensitized to peanut flour followed by exposure to amino acid diets fortified with peanut protein-polyphenol aggregates of either with low (15%; w/w) or high (40%; w/w) complexation ratios of blueberry (BB-Low and BB-High) and cranberry (CB-Low and CB-High) extracts. Treatment groups on diets with high complexation ratios of blueberry and cranberry aggregates showed significant reduction in peanut specific plasma Immunoglobulin E (IgE). Western blot analysis of spleen lysates showed CD63 protein expression was reduced in a dose-dependent manner in blueberry and cranberry complexed peanut protein supplemented diet groups. Our results demonstrate for the first time that complexation of polyphenols to peanut flour can potentially lower plasma IgE of peanut-sensitized C3H/HeJ mice.

Epitope-Resolved Detection of Peanut-Specific IgE Antibodies by Surface Plasmon Resonance Imaging.

Peanut allergy can be life-threatening and is mediated by allergen-specific immunoglobulin E (IgE) antibodies. Investigation of IgE antibody binding to allergenic epitopes can identify specific interactions underlying the allergic response. Here, we report a surface plasmon resonance imaging (SPRi) immunoassay for differentiating IgE antibodies by epitope-resolved detection. IgE antibodies were first captured by magnetic beads bearing IgE ϵ-chain-specific antibodies and then introduced into an SPRi array immobilized with epitopes from the major peanut allergen glycoprotein Arachis hypogaea h2 (Ara h2). Differential epitope responses were achieved by establishing a binding environment that minimized cross-reactivity while maximizing analytical sensitivity. IgE antibody binding to each Ara h2 epitope was distinguished and quantified from patient serum samples (10 μL each) in a 45 min assay. Excellent correlation of Ara h2-specific IgE values was found between ImmunoCAP assays and the new SPRi method.

The Relationship of Serum Antigen-Specific and Total Immunoglobulin E with Adult Cardiovascular Diseases.

Background: The relationship of serum antigen-specific immunoglobulin E (IgE) with cardiovascular diseases (CVDs) remains poorly understood. This study aimed to explore the association of antigen-specific and total IgE with CVDs using data derived from the National Health and Nutrition Examination Survey (NHANES) 2005-2006.Methods and Results: The association of serum total or antigen-specific IgE levels with CVDs was analyzed by survey-weighted logistic regression modeling, adjusted by age, sex, race, education, body mass index, blood pressure, total cholesterol, C-reactive protein, homocysteine, diabetes, smoking, and alcohol consumption. 4953 subjects were included. Coronary heart disease was significantly related to serum total IgE levels. The association of serum total IgE levels with coronary heart disease was further validated by negative, ≥1 and 1-6 positive antigen-specific IgE. Myocardial infarction was positively associated with serum total IgE levels only when all antigen-specific IgE were negative, but inversely associated with serum total IgE when plant-specific IgE test results were positive. More specifically, myocardial infarction was also inversely related to positive oak, birch, or peanut-specific IgE. In addition, serum total IgE are positively associated with angina when at least one specific IgE were positive.Conclusions: Serum antigen-specific IgE, as well as total IgE, is significantly associated with CVDs independently of a long list of established cardiovascular risk factors, which is more informative than total IgE per se.

Effects of combined high pressure and thermal treatment on the allergenic potential of peanut in a mouse model of allergy

Abstract Allergic reactions to peanut proteins are a worldwide concern. Ara h 2 in peanut (PN) is one of the most important peanut allergens ( Koppelman, Wensing, Ertmann, Knulst, & Knol, 2004 ), which is recognized by serum immunoglobulin E (IgE) from more than 90% of peanut-allergic individuals studied by Stanley et al., 1997 . Therefore, this study aimed at determining whether high pressure and thermal treatment could reduce the allergic properties of PN. Peanut protein extracts were treated with high pressure in 100–600 MPa and/or thermal treatment in 25–75 °C for 2.5–30 min, and the immunoreactivity of PN were analyzed by competitive inhibition enzyme-linked immunosorbent assays using pool sera from eight patients with peanut specific IgE. Compared to the boiling treatment, a significant reduction in IgE binding was observed when the samples were treated at 55 °C, 600 MPa for more than 10 min. Furthermore, in a BALB/c mouse model of allergy, significant reductions in specific IgE titers were observed in PN treated with high pressure and thermal (PNH) fed mice, accompanied by reduced histamine levels in serum. Similarly, real-time reverse transcription polymerase chain reaction revealed the decrease in mRNAs encoding interferon-γ, interleukin (IL)-4 and IL-10 in ileum tissues. PNH had almost no allergenicity in the BALB/c mouse model of PN allergy. Industrial relevance High hydrostatic pressure (HHP) processing can inactivate microorganisms and enzymes, leaving sensory and nutritional quality almost unchanged. Furthermore, HHP could alter allergen conformation and hence decrease allergenic activity in rice, fish, milk and celery that were reported. As a health concern, peanut allergies have been studied in this work. We determined whether high pressure and thermal could reduce the allergic properties of peanut allergen Ara h 2. In addition, effects of high pressure and thermal treatment on the peanut allergenicity of Ara h 2 (PNH) were characterized using a BALB/c mouse model of allergy.

Percentages of Activated and Proliferating T-Regulatory Cells Correlate with Peanut-Specific Immunoglobulin-E Level in Peanut Allergic Children

Percentages of Activated and Proliferating T-Regulatory Cells Correlate with Peanut-Specific Immunoglobulin-E Level in Peanut Allergic Children

Mucosal brush biopsy of the oral cavity to detect local, peanut‐specific immunoglobulin E

This study compares the ability of mucosal brush biopsy (MBB) from 2 separate locations in the oral cavity to detect peanut-specific immunoglobulin E (IgE) in patients who report adverse oral cavity reactions when ingesting peanuts. Twenty patients who reported a history of oral cavity itching or swelling when ingesting peanuts underwent either MBB of the dorsal tongue (n = 10) or the vestibule (n = 10). Serum testing for total and peanut-specific IgE, using standard immunofluorescent assay, was obtained for all patients. Total and specific IgE for each location were compared. Additionally, the correlation between MBB and peanut-specific IgE on serum was determined using Fisher's exact probability testing. Peanut-specific IgE was detected in 3 of 10 (30%) MBB specimens from the dorsal tongue and in 10 of 10 (100%) MBB specimens from the vestibule. The mean peanut-specific IgE on MBB (kU/L) in the dorsal tongue group was 0.03 vs 0.17 in the vestibule group (p = 0.0002). No significant association was noted for peanut-specific IgE between MBB and serum testing (p = 1.0). This study demonstrates for the first time that peanut-specific IgE can be detected using MBB in the oral cavity of patients who are symptomatic when consuming peanuts. The vestibule was a superior location compared to the dorsal tongue for oral cavity MBB, correlating very well with self-reported symptoms. Peanut-specific IgE on MBB overall did not correlate well with serum testing for peanut-specific IgE.

The natural history of persistent peanut allergy

BackgroundPeanut allergy affects 1% of children, and for those with persistent disease, few data have been published on trends in peanut-specific immunoglobulin E (P-IgE) levels or the value of P-IgE in predicting reaction severity. ObjectiveThe primary outcome was the frequency of inadvertent peanut exposure. Secondary outcomes included clinical characteristics, trends in P-IgE, characteristics of accidental exposures, and predictors of reaction severity in patients with persistent peanut allergy. MethodsRecords of patients with persistent peanut allergy were reviewed. Other allergic conditions, P-IgE levels, and peanut exposures were documented. ResultsSeven hundred eighty-two patients were studied, 524 of them male. The median age at initial observation was 1.4 years; the median duration of follow-up was 5.3 years. Of the 782 patients, 93.1% were avoiding other foods, 70.8% had atopic dermatitis, 57.3% allergic rhinitis, and 55.8% asthma. The median initial P-IgE was 28.0 kU/L, and the median peak P-IgE was 68.1. Six hundred eighty-five exposures were seen among 455 patients: 75.9% ingestion, 13.6% contact, 4.5% airborne. 73.7% resulted in urticaria/angioedema, 22.2% lower respiratory symptoms, 21.2% gastrointestinal symptoms, and 7.7% oral erythema/pruritus. Treatment included antihistamines (33.4%), emergency department visits (16.5%), epinephrine (13.1%), corticosteroids (7.7%), albuterol (3.2%), no treatment (26.3%), and not recorded (29.6%). The rate of postdiagnosis ingestion was 4.7%/year; exposures with severe reactions, 1.6%/year; reactions treated with epinephrine, 1.1%/year. Reaction severity did not change with repeated exposure. Severe reactions were associated with higher P-IgE, but not with age, sex, or asthma. ConclusionIn this referral population, the rates of accidental peanut exposures and severe reactions were low. There was a strong association between higher P-IgE levels and reaction severity.

DEVELOPMENT OF TRANSIENT PEANUT ALLERGY FOLLOWING BILATERAL LUNG TRANSPLANTATION: PASSIVE TRANSFER OF PEANUT-SPECIFIC IGE-SENSITIZED MAST CELLS FROM DONOR TO RECIPIENT

INTRODUCTION: Peanut allergy is one of the leading food-related allergies with significant morbidity and mortality. Immunoglobulin E (IgE)-mediated type 1 hypersensitivity to peanut is a leading cause of anaphylaxis. Anaphylaxis is a mast cell dependent process mediated by IgE. Mast cells sensitized by peanut-specific IgE can initiate the anaphylaxis cascade resulting in multisystem involvement, including cardiovas cular, respiratory, gastrointestinal, neurologic, and dermatological manifestations.

FACTORS ASSOCIATED WITH THE DEVELOPMENT OF PEANUT ALLERGY IN CHILDHOOD

Lack G, Fox D, Northstone K, Golding J. N Engl J Med. 2003;348:977–985Because peanut allergy has increased in prevalence and is an important cause of life-threatening reactions, the authors sought to investigate possible determinants of peanut allergy.Data were obtained from the Avon Longitudinal Study of Parents and Children. This geographically defined cohort included 13 971 preschool-aged children. Forty-nine of those children had a history of peanut allergy. Thirty-six of those 49 underwent skin testing, and 29 demonstrated positive results. Peanut allergy was confirmed for 23 children with double-blind, placebo-controlled, food challenge.Pregnant women were enrolled and questioned about their allergy history before delivery and were given serial questionnaires throughout their children’s infancy and childhood. The authors prospectively identified 49 children with a history of reactions to peanuts. Twenty-three children were then confirmed as being allergic to peanuts with skin testing and double-blind, placebo-controlled, food challenge. There were 2 control groups, including children with eczema in the first 6 months of life whose mothers also had eczema and 140 children without peanut allergy who were randomly selected from the cohort. Cord blood samples stored at birth were retrieved and analyzed for peanut-specific and total immunoglobulin E (IgE) for the children with peanut allergy. Retrospective data on maternal consumption of peanuts during pregnancy and lactation, family history of peanut allergy, and the use of specific lotions and creams (the interviewer was not aware of which products contained peanut oil) were then obtained.Peanut allergy was found to be independently associated with eczematous dermatitis (rash over joints and creases or oozing crusted rash) in the first 6 months of life, intake of soy products, family history of peanut allergy, and the use of skin preparations containing peanut oil. Neither maternal peanut consumption during pregnancy and lactation nor duration of breastfeeding was found to be associated with the development of peanut allergy. Additional evidence not supporting previous concepts of in utero sensitization came from undetectable peanut-specific IgE and normal total IgE levels in cord blood.Sensitization to peanut antigens appeared to be through inflamed atopic skin, rather than via the gastrointestinal tract, possibly from the use of skin preparations with even trace amounts of peanut oil. With respect to the independent association between intake of soy products and peanut allergy, soy protein fractions have shown homology to major peanut proteins and cross-sensitization could result from exposure to a common T cell epitope.With the increase in peanut allergy and other food allergies, elucidation of risk factors for prevention of sensitization offers new strategies to combat this food allergy epidemic. Allergic sensitization through the skin has also been proposed for the development of asthma and has been demonstrated in mouse models of atopic dermatitis. Additional studies are needed to determine whether topical peanut oil treatment is definitely a risk factor for peanut allergy; however, it seems prudent to avoid the topical use of peanut oil-containing products among children with atopic dermatitis. The finding of soy consumption being associated with peanut allergy may be attributable to the increased likelihood of food-allergic children receiving soy products, rather than a specific association with peanut allergy. Confirmation of this association is needed.

Serological characteristics of peanut allergy in children.

Food challenge is considered an excellent clinical tool for the diagnosis of specific food allergy. However in the case of peanut allergy it may be difficult to perform because of the severity of the reactions. The quantitation of a specific immunoglobulin E (IgE) response to different peanut allergens could also contribute to the improvement of the diagnosis. We characterized the IgE response to a whole peanut protein extract and to Ara h 1 and Ara h 2 in different groups of patients classified according to the severity of their allergic reactions. Specific serum IgE were analyzed in 96 children by enzyme-linked immunosorbent assay tests using a whole protein extract or purified peanut proteins and anti-human IgE monoclonal antibodies labeled with acetylcholinesterase. A parallel was observed between levels of peanut-specific IgE and the classification in five groups and subgroups of patients upon increasing severity of symptoms, especially within the group of highest severity. Moreover, the highest frequency of positive response and the highest levels of specific IgE were observed with whole peanut protein extract. In a retrospective evaluation of peanut allergy in children, we have shown that quantitation of peanut-specific IgE could be used to avoid a food challenge particularly in the case of severe reactions. When compared to Ara h 1 and Ara h 2, whole peanut protein extract appeared to be the most appropriate allergen to perform the test.

The Natural History of Peanut Allergy in Young Children and Its Association with Serum Peanut-Specific IgE

Purpose of the Study. To characterize adverse reactions after accidental peanut exposure in young children with peanut allergy and to determine the usefulness of serum peanut-specific immunoglobulin E (IgE) levels during follow-up.Study Population. One hundred two children were identified who had clinical peanut hypersensitivity before 4 years of age. Inclusion criteria included 1) a convincing history of clinical peanut hypersensitivity and/or a positive double-blind, placebo-controlled food challenge (DBPCFC) response to peanuts and 2) a positive skin prick test response to peanuts.Methods. Research subjects were contacted at least yearly to track adverse reactions caused by accidental exposure to peanuts. Nineteen participants discontinued their participation in the study or were lost to follow-up, leaving 83 for inclusion in the analysis. Peanut-specific serum IgE levels were determined in 51 of 83 subjects using the Pharmacia CAP system (Uppsala, Sweden).Results. Thirty-one of 53 (58%) of the subjects followed for 5 years experienced adverse reactions from accidental peanut exposure. Regardless of the nature of their initial reaction, the majority with subsequent reactions (31/60; 52%) experienced potentially life-threatening symptoms. The group with isolated skin symptoms (11/51; 22%) had lower serum peanut-specific IgE levels (median: 1.25 kUa/L vs 11.65 kUa/L; P = .004; Wilcoxan rank sum) than the group with respiratory and/or gastrointestinal symptoms (40/51; 78%). There was no threshold level below which only skin symptoms appeared to occur. Of note, 4 subjects had negative DBPCFC results to peanuts during the follow-up period.Conclusions. The majority of children with peanut allergy followed for up to 5 years will have adverse reactions from accidental peanut exposure. Symptoms may not be consistent with symptoms reported during initial reactions. A minority of children with peanut allergy can lose their clinical hypersensitivity.Reviewer’s Comments. This report addresses 2 common questions asked by parents of children with peanut allergy: a) will the reactions become progressively worse? and b) will the reactions ever subside? Despite appropriate counseling on peanut avoidance, the majority of the children experienced an accidental peanut ingestion during follow-up. Moreover, initial clinical reactions involving only the skin can subsequently progress to involve the respiratory and/or gastrointestinal systems. A minority of subjects with low serum peanut-specific IgE levels developed oral tolerance to peanut. This investigation has expanded the growing body of evidence in this research area and has provided practical clinical information for addressing allergic reactions to peanuts. With the inevitability of accidental ingestions, the general trend for worsening of clinical reactions with subsequent exposures, and the inability to predict severity of future reactions, the take-home messages should be that all patients with peanut allergy need proper education about the potential seriousness of future accidental exposures and self-injectable epinephrine to manage future, severe allergic reactions.

Subsequent reactions were common and often more serious than the initial reactions of children with peanut allergy

(2000) J Pediatr 137, 749. Vander Leek TK, Liu AH, Stefanski K, et al. . The natural history of peanut allergy in young children and its association with serum peanut-specific...