IgE-mediated Food Allergy Research Articles

Characterization of Mouse Anti-Crude Peanut Extract IgE Monoclonal Antibodies

Abstract INTRODUCTION: Immediate hypersensitivity reactions to peanuts, an IgE-mediated food allergy, are a major public health concern. For allergic patients, avoidance currently remains the only viable option. Mouse peanut allergy models are used for studying pathogenesis and therapeutics, However, establishing animal models with high IgE antibody titers is difficult. OBJECTIVE: Newly developed mouse anti-crude peanut extract (CPE) IgE monoclonal antibodies (mAbs) were evaluated with in-vitro and in-vivo assays used for studying the pathogenesis of and therapeutics against peanut allergies. METHODS and RESULTS: Four hybridomas that produce IgE mAbs against CPE were established from BALB/c mice orally administrated CPE with cholera toxin. All mAbs recognized the Ara h1 allergen in CPE by western blot and worked dose dependently in sandwich ELISAs using an anti-IgE capture mAb and biotinylated CPE. However, only three mAbs worked in indirect ELISAs with CPE coated plates, depending on individual epitope specificities. The three mAbs degranulated RBL-2H3 cells and their degrees of activation varied by mAbs and concentration. In female BALB/c mice, two mAbs developed footpad delayed type hypersensitivity, which peaked at 1–2 hours after sensitization and drop in body temperature in anaphylaxis reactions, which peaked at 40–60 minutes after an IV injection of CPE. CONCLUSION: Two out of four IgE mAbs can work for both in-vitro and in-vivo peanut allergy studies. Particularly, the mAbs can develop allergic reactions with sensitization alone in mice. This will be especially useful to evaluate therapeutic methods associated with mast cell activation as the mAbs can accelerate studies with no lengthy immunization protocols.

Changes in risk factors for food sensitization in early life: Analysis over a period of 10 years.

Although epidemiological trends of childhood food sensitization (FS) in IgE-mediated food allergy were reported in China, few studies have examined at changes in its risk factors. To investigate the change in early-life risk factors associated with childhood food sensitization during 2009-2019 in China. Data from two cross-sectional surveys conducted in 2009 and 2019 (401 and 513 children, respectively) were analyzed. The results of skin prick tests and information on food sensitization-related risk factors in children were summarized, including family history of atopic disease (FHA), demographic characteristics, method of delivery, feeding patterns, sibship size, pet ownership, and vitamin D supplementation. Binary logistic regression was used to calculate the odds ratio and the regression coefficient β-value of risk factors in the 2009 and 2019 surveys separately. Then, coefficient β-value differences between the two surveys were analyzed by the bdiff command in STATA to describe the change in risk factors over 10 years. The 2009 survey revealed that FHA, age, only child, and feeding patterns were associated with food sensitization. The 2019 survey showed that food sensitization was affected by age, sex, and feeding patterns. However, from 2009 to 2019, the probability of food sensitization in the only-child group significantly increased by 226.0% (β-value difference = 0.81, P = 0.024) and decreased by 65.0% in female children (β-value difference = -1.06, P = 0.008). The effect of age on food sensitization decreased by 50.0% (β-value difference = -0.69, P < 0.001) over 10 years. The effect of FHA and common lifestyle factors on food sensitization did not significantly change during 2009-2019. However, the influence of demographic characteristics on food sensitization has changed since 2009; that is, older age, male gender, and only child are more likely to develop food sensitization, which needs to be considered in future epidemiological surveys. http://www.chictr.org.cn/, identifier ChiCTR1900024338.

Biologicals in IgE-mediated food allergy.

A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy. A systematic review and meta-analysis demonstrated safety and effectiveness of omalizumab in the treatment of food allergy. The findings support the potential use of omalizumab as a monotherapy or as an adjunct to oral immunotherapy in IgE-mediated cow's milk allergy. The potential use of other biologics in the management of food allergy is subject of speculation. Different biological therapies are under evaluation for food allergic patients. The advance in literature will guide for a personalized treatment in the near future. However, additional research is needed to better understand the best candidate for each treatment, the optimal dose and timing.

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease.

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

The advances of allergen component detection in IgE-mediated food allergy

There are many types in food allergy, and the most common is mediated by IgE. Currently, the diagnosis of food allergy mainly relied on skin prick test and serum specific IgE of allergen extract, which can not identify cross-sensitization. Component-resolved diagnosis (CRD) can identify the major allergen components and cross-components of food allergens, which plays an important role in dietary guidance, prognosis monitoring and diagnosis of special types of IgE-mediated food allergy. This article enumerates clinical characteristics of the IgE-mediated common food allergies, such as milk, egg and seafood allergy, and special type of food allergy, such as cat pork syndrome, oral allergy syndrome, α-gal syndrome and food-dependent exercise-induced anaphylaxis, summarizes the advances of CRD in these types of IgE-mediated food allergy, in order to provide an evidence for the diagnosis, treatment and prevention of IgE-mediated food allergy.

Targeting type 2 immunity and the future of food allergy treatment.

IgE-mediated food allergy affects 6-8% of the population in the United States. Type 2 immune responses are central to the pathogenesis of food allergy, but type 2 CD4+ T cell responses have been found to be heterogeneous in food allergy suggesting a division of labor between Tfh13 and peTH2 cells in promotion of IgE class switching, modulation of intestinal barrier function, and regulation of mast cell expansion. Oral immunotherapy for the treatment of food allergy incompletely targets subsets of type 2 immunity in a transient manner, but new therapeutics targeting different levels of type 2 immunity are in current or planned trials for food allergy. These new treatments and the basis for their use are the focus of this review.

Safety of mRNA vaccination for COVID‐19 in children with polyethylene glycol (PEG)‐asparaginase allergy

Safety of <scp>mRNA</scp> vaccination for <scp>COVID</scp>‐19 in children with polyethylene glycol (<scp>PEG</scp>)‐asparaginase allergy

A Qualitative Study to Inform Development of a Behavioral Intervention to Promote Food Allergy Self-Management and Adjustment among Early Adolescents.

Adolescence is a high-risk period for patients with food allergy (FA) as management responsibilities shift to the youth. This study used qualitative methods to explore FA experiences among a diverse pediatric FA population and inform behavioral intervention development. A total of 26 adolescents ages 9-14 years with IgE-mediated FA (M age = 11.92 years; 62% male; 42% Black, 31% White, 12% Hispanic/Latinx) and 25 primary caregivers (M age = 42.57 years; 32% annual income > $100,000) were recruited from FA clinics to complete separate qualitative interviews about FA-related experiences. Interviews were audio-recorded, transcribed, and entered into Dedoose, a qualitative software program. A grounded theory qualitative analytic approach was used to analyze data. Emergent themes include: 1) FA is a chronic burden that affects daily life, 2) Families experience anxiety about FA, 3) Families find it challenging to transition FA management from parent to child, 4) FA families feel the need to be prepared, 5) FA families frequently advocate for their needs, and 6) Social experiences affect the FA experience. Adolescents with FA and their caregivers experience daily stress related to their chronic illness. A behavioral intervention that provides FA education, bolsters stress/anxiety management, assists parents in transitioning FA management responsibility to the youth, teaches executive functioning and advocacy skills, and fosters peer support could help adolescents successfully cope with and manage FA in their daily lives.

Delayed‐type hypersensitivity gastrointestinal symptoms induced by food oral immunotherapy and efficiently treated by dupilumab: A case report

Delayed‐type hypersensitivity gastrointestinal symptoms induced by food oral immunotherapy and efficiently treated by dupilumab: A case report

Food protein-induced enterocolitis syndrome: Healthcare utilization and referral patterns among a pediatric cohort.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy characterized by delayed, repetitive vomiting. FPIES is improving in recognition; however, there remains a lag in diagnosis. This study aimed to further explore this lag, as well as referral patterns and healthcare utilization, to help determine areas for earlier recognition. A retrospective chart review of pediatric FPIES patients at two hospital systems in New York was completed. Charts were reviewed for FPIES episodes and healthcare visits prior to diagnosis, and reason/source of referral to an allergist. A cohort of patients with IgE-mediated food allergy was reviewed for comparison of demographics and the time to the diagnosis. In total, 110 patients with FPIES were identified. The median time to diagnosis was 3 months, vs. 2 months in IgE-mediated food allergy (p < 0.05). Most referrals were from the pediatrician (68%) or gastroenterology (28%), none were from the ED. The most common reason for referral was concern of IgE-mediated allergy (51%), followed by FPIES (35%). There was a statistically significant difference in race/ethnicity between the FPIES cohort and IgE-mediated food allergy group (p < 0.0001), with a greater proportion of Caucasian patients in FPIES vs. IgE-mediated food allergy cohort. This study demonstrates a lag in the diagnosis of FPIES and a lack of recognition outside of the allergy community, as only one-third of patients were considered to have FPIES prior to an allergy evaluation.

Acute systemic myeloid inflammatory and stress response in severe food allergic reactions.

Food allergic reactions can be severe and potentially life-threatening and the underlying immunological processes that contribute to the severity of reactions are poorly understood. The aim of this study is to integrate bulk RNA-sequencing of human and mouse peripheral blood mononuclear cells during food allergic reactions and in vivo mouse models of food allergy to identify dysregulated immunological processes associated with severe food allergic reactions. Bulk transcriptomics of whole blood from human and mouse following food allergic reactions combined with integrative differential expressed gene bivariate and module eigengene network analyses to identify the whole blood transcriptome associated with food allergy severity. In vivo validation immune cell and gene expression in mice following IgE-mediated reaction. Bulk transcriptomics of whole blood from mice with different severity of food allergy identified gene ontology (GO) biological processes associated with innate and inflammatory immune responses, dysregulation of MAPK and NFkB signalling and identified 429 genes that correlated with reaction severity. Utilizing two independent human cohorts, we identified 335 genes that correlated with severity of peanut-induced food allergic reactions. Mapping mouse food allergy severity transcriptome onto the human transcriptome revealed 11 genes significantly dysregulated and correlated with severity. Analyses of whole blood from mice undergoing an IgE-mediated reaction revealed a rapid change in blood leukocytes particularly inflammatory monocytes (Ly6Chi Ly6G- ) and neutrophils that was associated with changes in CLEC4E, CD218A and GPR27 surface expression. Collectively, IgE-mediated food allergy severity is associated with a rapid innate inflammatory response associated with acute cellular stress processes and dysregulation of peripheral blood inflammatory myeloid cell frequencies.

Inhibition of pathologic immunoglobulin E in food allergy by EBF-2 and active compound berberine associated with immunometabolism regulation.

Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production. IgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE+ plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated. EBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line. EBF-2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders.

Utilizing metabolomics to define biomarkers of reaction severity in IgE-mediated food allergy

Clinicians currently do not have reliable biomarkers to predict the risk of severe allergic reactions to food. Our aim was to identify baseline biomarkers of an altered metabolic state that may predict food allergy severity.

Soluble IgE-binding factors in the serum of food-allergic patients: Possible pathophysiological role of soluble FcεRI asprotective factor.

IgE-mediated food allergy is the result of an aberrant immune response involving the interaction of a food allergen with its specific IgE bound to FcɛRI, the high affinity IgE receptor, on mast cells. Allergen-specific IgE also binds to soluble binding factors, but, their expression and role in food allergy is not well characterized. Here, we assess the prevalence and relevance of soluble IgE binding factors in food allergy and tolerance. We measured serum levels of four IgE binding factors, that is, galectin-3, galectin-9, soluble FcɛRI (sFcεRI) and soluble CD23 (sCD23) in 67 adults sensitized to peanut or hazelnut and sFcɛRI in 29 children sensitized to hen's egg. Adults without food allergen sensitization (n=17) served as healthy controls. We compared serum levels of patients and controls and assessed them, in the former, for links to clinical features including allergy and tolerance. Serum levels of sFcɛRI and sCD23, but not galectin-3 and galectin-9, significantly differ in food-sensitized patients as compared to healthy controls. A subgroup (28%) of peanut and hazelnut allergic patients had elevated sFcεRI levels, that were associated with higher total and specific IgE levels. Furthermore, sFcεRI levels were significantly higher in tolerant subjects compared to allergics. Among hazelnut allergic patients, those with high sFcεRI levels tolerated the highest protein amounts in the oral food challenge. sFcɛRI but not sCD23, galectin-3 and galectin-9 might play a role in the pathophysiology of food allergy. Its functional role or use as biomarker should be assessed in further studies.

Maternal Attitudes during Pregnancy regarding Food Allergy Prevention in Offspring

IgE-mediated food allergy has significant medical consequences and health-related costs; there is currently no cure once persistent food allergy has been established. In 2017, updated U.S. guidelines recommended early introduction of peanut for the prevention of food allergy in at-risk infants. Implementation of these guidelines is inconsistent. Given the limited window of opportunity for peanut introduction in infancy, providing anticipatory guidance during pregnancy may be important.

Determinants of Quality of Life in Patients with IgE-Mediated Food Allergy

Determinants of Quality of Life in Patients with IgE-Mediated Food Allergy

Management of Eosinophilic Esophagitis in Pediatric Patients Undergoing Food Allergen Oral Immunotherapy

Oral immunotherapy (OIT) is a promising treatment for food allergy, however, some patients cannot initiate or continue OIT if they develop eosinophilic esophagitis (EoE). Here we present the management and outcomes of pediatric patients with EoE and being treated with concurrent OIT for IgE-mediated food allergy.

Distribution and Determinants of Developing Tolerance to Food Allergens in a Large US Population-based Sample of Children and Adults

Food allergy (FA) is a major public health problem estimated to affect 1 in 10 Americans. Little work to date has aimed to systematically characterize the distribution and determinants of food tolerance among children and adults meeting established criteria for IgE-mediated FA.

Atopy and allergy following solid organ transplantation: A 15-year experience.

There are increasing reports of atopy/allergy following solid organ transplantation, especially paediatric liver transplantation (LT) with minimal New Zealand (NZ) data. We describe the prevalence of transplant-acquired atopy and allergy (TAA) in NZ paediatric liver transplant recipients, compared to paediatric kidney and adult liver transplants. TAA focussed health questionnaires were sent to patients selected from the NZ transplant registry (transplanted between January 2003 and December 2017). Demographic and clinical data were also obtained from electronic health records and follow-up phone calls. A total of 232 patients (62% male) participated (111 adult liver, 82 paediatric liver, 39 paediatric kidney transplant recipients). Tacrolimus was primary immunosuppression for all LT patients; with combined tacrolimus, mycophenolate and corticosteroids for kidney transplants. The number of patients who developed TAA was significantly higher (P< 0.001) in the paediatric LT group (36/82, 44%) compared to adult liver (12/111, 11%) and paediatric kidney transplants (4/39, 10%). Eczema was most common (73%), then IgE-mediated food allergy (FA, 33%), allergic rhinitis (19%) and asthma (17%). Six paediatric LT recipients developed eosinophilic oesophagitis (EoE). Egg was the most common allergen in the IgE-mediated FA group. TAAs were severe enough to warrant a switch from tacrolimus to another agent in seven paediatric LT patients. For paediatric LT patients, female gender and younger age at transplant were risk factors for developing TAA. TAA is common in paediatric liver transplant recipients, with female gender and younger age at transplant being risk factors identified. This highlights the need for detailed atopic and allergy history to be incorporated in all pre-transplant assessments.

The Need for Required Stock Epinephrine in All Schools: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee

Epinephrine is the first line of treatment for anaphylaxis which can occur outside a medical setting in community environments like schools. Patients with diagnosed IgE-mediated food allergy at risk of anaphylaxis are prescribed self-injectable epinephrine and given an individualized anaphylaxis action plan. As students, such patients/families provide their school with completed medication forms, a copy of their anaphylaxis plan, and additional student-specific epinephrine. However, students approved to self-carry prescribed self-injectable epinephrine may forget to do so or have other reasons for lacking prescribed epinephrine such as familial inability to fill the prescription due to cost or other access barriers. Undiagnosed students lacking prescribed epinephrine may also experience anaphylaxis at school. The presence of non-student specific school stock epinephrine allows school nurses and other staff the ability to treat anaphylaxis on-site while awaiting emergency medical services. Notably, not all states legally mandate K-12 schools to stock epinephrine. In states with laws only voluntarily allowing schools to stock epinephrine, it provides the ability to opt-out. Herein, we present a comprehensive review of barriers to school stock epinephrine, related improvement strategies, and workgroup recommendations supporting the need for mandated stock epinephrine in all schools in every state. Proposed solutions include ensuring legal immunity from liability for prescribers; advocacy for legislation to stabilize cost of self-injectable epinephrine; educational initiatives to schools promoting merits and safety of epinephrine and related anaphylaxis training; and partnerships between patient advocacy groups, medical and nursing organizations, public health departments and other health professionals to promote laws and district policies addressing need for stock epinephrine and school nurses to train and supervise school staff.