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Continuing insight into the molecular mechanisms of atopic disorders has enabled the development of biologics to precisely target these diseases. Food allergy (FA) and eosinophilic gastrointestinal disorders (EGIDs) are driven by similar inflammatory molecular mechanisms and exist along the same atopic disease spectrum. Therefore, many of the same biologics are being investigated to target key drivers of mechanisms shared across the disease states. The enormous potential of biologics for the treatment of FA and EGIDs is highlighted by the significant increases in the number of ongoing clinical trials (more than 30) evaluating their use in these disease states, as well as by the recent US Food and Drug Administration approval of dupilumab for the treatment of eosinophilic esophagitis. Here we discuss past and current research into the use of biologics in FA and EGIDs and their potential role in improving treatment options in the future, with the need to have biologics widely clinically available. [ABSTRACT FROM AUTHOR]

Type 2 allergen‐specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen‐specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance. We sought to identify regulatory components of the CD4+ T‐cell response to food allergens by studying their functional activation over time in vitro and in vivo. Two subsets of Tregs expressing CD137 or CD25/OX40 were identified with a delayed kinetics of activation compared with clonally enriched pathogenic effector Th2 cells. Treg activation was dependent on IL‐2 derived from effector T cells. In vivo exposure to peanut in the form of an oral food challenge of allergic subjects induced a delayed and persistent activation of Tregs after initiation of the allergen‐specific Th2 response. The novel finding of our work is that a sustained wave of Treg activation is induced by the release of IL‐2 from Th2 effector cells, with the implication that therapeutic administration of IL‐2 could improve current OIT approaches. [ABSTRACT FROM AUTHOR]

Background: Health‐related quality of life (HRQoL) is significantly and substantially reduced in individuals with peanut allergy due to many factors associated with unanticipated or potentially fatal reactions. Further insight on the impact of peanut oral immunotherapy in managing peanut allergy on HRQoL is needed. The aim of this analysis was to assess effects of peanut (Arachis hypogaea) allergen powder‐dnfp (PTAH), a biologic drug for peanut oral immunotherapy, on HRQoL from three phase 3 and two follow‐on trials of PTAH. Methods: HRQoL assessments from participants aged 4–17 in the PALISADE (ARC003), ARC004 (PALISADE follow‐on), ARTEMIS (ARC010), RAMSES (ARC007), and ARC011 (RAMSES follow‐on) trials were included in this analysis. Responses on the Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) were evaluated by age group and respondent (self or caregiver proxy). Data were analyzed with descriptive statistics and Student t tests. Results: Baseline FAQLQ and FAIM total scores appeared comparable between PTAH‐ and placebo‐treated participants. Self and caregiver proxy‐reported total scores on the FAQLQ for PTAH‐treated participants generally improved at trial exit versus baseline; FAIM total scores improved throughout all trials. The tendency for improvement in FAQLQ total scores from baseline for PTAH appeared larger in self versus caregiver proxy‐reports. Between treatment groups, PTAH was generally favored in the PALISADE and ARTEMIS trials; differences varied in the RAMSES trial based on age and respondent types. Conclusions: PTAH for the management of peanut allergy in children appeared to have a beneficial effect on HRQoL in trials. Improvements were seen despite rigors of trial participation. [ABSTRACT FROM AUTHOR]

[Display omitted] Reaction threshold and severity in food allergy are difficult to predict, and noninvasive predictors are lacking. We sought to determine the relationships between pre-challenge levels of peanut (PN)-specific antibodies in saliva and reaction threshold, severity, and organ-specific symptoms during PN allergic reactions. We measured PN-specific antibody levels in saliva collected from 127 children with suspected PN allergy before double-blind, placebo-controlled PN challenges in which reaction threshold, severity, and symptoms were rigorously characterized. Low threshold (LT) PN allergy was defined as reaction to <300 mg of PN protein cumulatively consumed. A consensus severity grading system was used to grade severity. We analyzed associations between antibody levels and reaction threshold, severity, and organ-specific symptoms. Among the 127 children, those with high pre-challenge saliva PN IgE had higher odds of LT PN allergy (odds ratio [OR] 3.9, 95% CI 1.6-9.5), while those with high saliva PN IgA:PN IgE ratio or PN IgG 4 :PN IgE ratio had lower odds of LT PN allergy (OR 0.3, 95% CI 0.1-0.8; OR 0.4, 95% CI 0.2-0.9). Children with high pre-challenge saliva PN IgG 4 had lower odds of severe PN reactions (OR 0.4, 95% CI 0.2-0.9). Children with high saliva PN IgE had higher odds of respiratory symptoms (OR 8.0, 95% CI 2.2-26.8). Saliva PN IgE modestly correlated with serum PN IgE levels (Pearson r = 0.31, P =.0004). High and low saliva PN IgE levels further distinguished reaction threshold and severity in participants stratified by serum PN IgE, suggesting endotypes. Saliva PN antibodies could aid in noninvasive risk stratification of PN allergy threshold, severity, and organ-specific symptoms. [ABSTRACT FROM AUTHOR]

Health disparities are health differences linked with economic, social, and environmental disadvantage. They adversely affect groups that have systematically experienced greater social or economic obstacles to health. Renewed efforts are needed to reduced health disparities in the United States, highlighted by the disparate impact on racial minorities during the coronavirus pandemic. Institutional or systemic patterns of racism are promoted and legitimated through accepted societal standards, and organizational processes within the field of medicine, and contribute to health disparities. Herein, we review current evidence regarding health disparities in allergic rhinitis, asthma, atopic dermatitis, food allergy, drug allergy, and primary immune deficiency disease in racial and ethnic underserved populations. Best practices to address these disparities involve addressing social determinants of health and adopting policies to improve access to specialty care and treatment for the underserved through telemedicine and community partnerships, cross-cultural provider training to reduce implicit bias, inclusion of underserved patients in research, implementation of culturally competent patient education, and recruitment and training of health care providers from underserved communities. Addressing health disparities requires a multilevel approach involving patients, health providers, local agencies, professional societies, and national governmental agencies. [ABSTRACT FROM AUTHOR]

Abstract: Food allergy is increasingly common in children, affecting about 4%‐8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance, and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen‐contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen‐presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non‐vascularized epidermis limits systemic absorption, contributing to the high‐safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper‐responsiveness, and immunologic parameters. Several clinical trials of EPIT have recently been completed or are ongoing. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following 1 year of therapy is less than that seen compared to high‐dose (2‐4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears to lead to increasing desensitization. Additional data from larger‐scale studies should provide a more robust assessment of safety and efficacy of EPIT. [ABSTRACT FROM AUTHOR]

Background: Food allergies affect up to 8% of children, and milk and egg allergies are the most common triggers. Accurately diagnosing these food allergies is important to prevent allergic reactions and to avoid unnecessary dietary restrictions. However, positive skin-prick tests and detectable levels of serum food specific immunoglobulin E (IgE) alone may not be diagnostic for food allergy. Advances in the identification of relevant allergens and the development of recombinant proteins now allow assessment of IgE binding to individual proteins within a food. Component-resolved diagnostics (CRD) have the potential to provide more accurate assessments of clinical reactivity tofood allergens. Objective: To examine the available data for CRD for milk and egg allergies. Methods: This review discussed studies that evaluated the utility of CRD for guiding decisions about food challenges for milk and egg. Results: Residts of studies indicated that CRD may offer increased specificity, but sensitivity was lacking when compared with standard skin-prick testing and measurement of serum food specific IgE levels. Conclusion: The role of CRD in the diagnosis and management of milk and egg allergies is not well established at this time. Further studies are needed to explore the diagnostic value of CRD for milk and egg allergies. [ABSTRACT FROM AUTHOR]

Background: The growing prevalence of food allergies indicates a responsibility among primary care providers to ensure that their patients receive accurate diagnosis and management. Objective. To improve physician knowledge and management offood allergies by implementing educational and electronic medical record interventions. Methods: Pre- and posttest scores of pediatric residents and faculty were analyzed to assess the effectiveness of an educational session designed to improve knowledge of food allergy management. One year later, a best practice advisory was implemented in the electronic medical record to alert providers to consider allergy referral whenever a diagnosis code for food allergy or epinephrine autoinjector prescription was entered. A review of charts 6 months before and 6 months after each intervention was completed to determine the impact of both interventions. Outcome measurements included referrals to an allergy clinic, prescription of self-injectable epinephrine, and documentation that written emergency action plans were provided. Results: There was a significant increase in test scores immediately after the educational intervention (mean, 56.2 versus 84.3%; p < 0.001). Posttest scores remained significantly higher than preintervention scores 6 months later (mean score, 68.0 versus 56.2%; p = 0.006). Although knowledge improved, there was no significant difference in the percentage of patients who were provided allergy referral, were prescribed an epinephrine autoinjector, or were given an emergency action plan before and after both interventions. Conclusion: Neither intervention resulted in improvements in the management of children with food allergies at our pediatrics clinic. Further studies are needed to identify effective strategies to improve management of food allergies by primary care physicians. [ABSTRACT FROM AUTHOR]

The article highlights several studies on the diagnosis and treatment of children with allergy and immunologic diseases. Topics mentioned include the safety of topical corticosteroids, the risk of peanut allergy to infants, allergy to penicillin, the management of asthma, and the immune response of children against COVID-19.

Background Studies show that anaphylaxis is under-recognized and epinephrine (adrenaline) is under-used by medical personnel as well as patients and their families. This study assesses the knowledge of food-induced anaphylaxis diagnosis and management across different populations of providers and caregivers and other interested respondents. Methods An online survey embedded in a case discussion of food-induced anaphylaxis was distributed by Medscape to registered members. Results A total of 7822 responders who started the activity chose to answer at least some of the questions presented (response rate 39.5%). Over 80% of responders in all groups correctly identified the case of anaphylaxis with prominent skin and respiratory symptoms; however, only 55% correctly recognized the case without skin symptoms as anaphylaxis. Only 23% of responders correctly selected risk factors for anaphylaxis, with physicians significantly more likely to choose the correct answers as compared to allied health, other health professionals, and medical students (p < 0.001). Ninety-five percent selected epinephrine (adrenaline) as the most appropriate treatment for anaphylaxis, and 81% correctly indicated that there are no absolute contraindications for epinephrine (adrenaline) in the setting of anaphylaxis. When presented a case of a child with no documented history of allergies who has symptoms of anaphylaxis, more physicians than any other group chose to administer stock epinephrine (adrenaline) (73% vs. 60%, p < 0.001). Conclusion Specific knowledge deficits for food-induced anaphylaxis persist across all groups. Further educational efforts should be aimed not only at the medical community but also for the entire caregiver community and general public, to optimize care for food allergic individuals. [ABSTRACT FROM AUTHOR]

Food allergies affect up to 6% of young children and 3%-4% of adults. They encompass a range of disorders that may be IgE and/or non-IgE mediated, including anaphylaxis, pollen food syndrome, food-protein-induced enterocolitis syndrome, food-induced proctocolitis, eosinophilic gastroenteropathies, and atopic dermatitis. Many complex host factors and properties of foods are involved in the development of food allergy. With recent advances in the understanding of how these factors interact, the development of several novel diagnostic and therapeutic strategies is underway and showing promise. [ABSTRACT FROM AUTHOR]

Food allergy affects up to 6% of children and 3-4% of adults in Westernized countries, and is the most common cause of outpatient anaphylaxis in most studies. The mainstay of treatment is strict avoidance of the offending allergens and education regarding the use of emergency medication in cases of accidental ingestions or exposures. While these approaches are generally effective, there are no definitive treatments that cure or provide long-term remission from food allergy. However, with recent advances in characterizing food allergens and understanding humoral and cellular immune responses in food allergy, several therapeutic strategies are being investigated. Potential treatments include allergen-specific immunotherapy as well as allergen-nonspecific approaches to downregulate the overall allergic response in food-allergic individuals. [ABSTRACT FROM AUTHOR]

Background: In vitro testing is commonly used to diagnose and manage allergies. Clinical reactivity has been correlated with food-specific IgE levels by using the ImmunoCAP (Phadia, Uppsala, Sweden). Objective: To determine whether IgE levels derived from different assays are equivalent to those measured by ImmunoCAP. Methods: Fifty patients from the Mount Sinai Pediatric Allergy practice were prospectively enrolled. For each deidentified sample, specific IgE levels were measured to egg, milk, peanut, cat, birch, and Dermatophagoides farinae at different laboratories, each using a different assay system (Phadia ImmunoCAP, Agilent Turbo-MP, and Siemens Immulite 2000). Results were analyzed to determine whether IgE measurements were equivalent. Food allergen–specific IgE levels were correlated with clinical data and around empirically determined thresholds that predict probability of clinical disease in 50% or 95% of subjects. Results: Variable degrees of agreement existed among the 3 assays. Immulite 2000 overestimated all specific IgE levels compared with ImmunoCAP. Turbo-MP overestimated for egg but underestimated for birch and D farinae. Differences for milk, peanut, and cat were observed, without a trend toward overestimation or underestimation. Furthermore, several values for the food allergens were discrepant around the 50% and 95% positive predictive values for clinical reactivity. Conclusion: Discrepancies in specific IgE values from 3 different assays can potentially lead to altered management and treatment. The predictive values for clinical reactivity associated with food-specific IgE levels determined by ImmunoCAP should not be applied to results from other assays. [Copyright &y& Elsevier]

Anaphylaxis is a life-threatening allergic reaction, and food is one of the most common responsible allergens in the outpatient setting. The prevalence of food-induced anaphylaxis has been steadily rising. Education regarding food allergen avoidance is crucial as most of the fatal reactions occurred in those with known food allergies. The lack of a consensus definition for anaphylaxis has made its diagnosis difficult. Symptoms affect multiple organ systems and include pruritus, urticaria, angioedema, vomiting, diarrhoea, abdominal cramps, respiratory difficulty, wheezing, hypotension, and shock. Prompt recognition of anaphylaxis is essential as delayed treatment has been associated with fatalities. Although epinephrine is accepted as the treatment of choice, timely administration does not always occur, partly due to a lack of awareness of the diagnostic criteria. Several novel tools are currently being investigated, which will potentially aid in the diagnosis and treatment of food-induced anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: Asthma continues to be an increasing cause of morbidity in the pediatric population, and studies have shown an association between food sensitivity and asthma. Objective: We investigated the degree of food allergen sensitization in inner-city patients with asthma. Methods: Five hundred four random serum samples from the National Cooperative Inner City Asthma Study were evaluated for specific IgE (UniCap) to 6 common food allergens (egg, milk, soy, peanut, wheat, and fish). Statistical analyses were performed to determine food sensitization prevalence and its association with asthma morbidity. Results: Forty-five percent of patients had evidence of sensitization (food-specific IgE ≥0.35 kU/L) to at least 1 food. Nineteen percent had IgE levels at ≥50% positive predictive value for clinical reactivity to at least 1 food, with 4% of patients having levels >95% positive predictive value for food allergy. Children sensitized to foods had higher rates of asthma hospitalization (P < .01) and required more steroid medications (P =.025). Sensitization to foods also correlated with sensitization to more indoor and outdoor aeroallergens (P < .001). Conclusion: Food allergen sensitization is highly prevalent in the inner-city population with asthma, and it is associated with increased asthma healthcare and medication use. Therefore, food allergen sensitivity may be a marker for increased asthma severity. [Copyright &y& Elsevier]

Background Methods Results Conclusions Limited decision‐support tools are available to help shared decision‐making (SDM) regarding food oral immunotherapy (OIT) initiation. No current tool covers all foods, forms, and pediatric ages for which OIT is offered.In compliance with International Patient Decision Aid Standards criteria, this pediatric decision‐aid comparing OIT versus avoidance was developed in three stages. Nested qualitative data assessing OIT decisional needs were supplemented with evidence‐synthesis from the OIT literature to create the prototype decision‐aid content. This underwent iterative development with food allergy experts and patient advocacy stakeholders until unanimous consensus was reached regarding content, bias, readability, and utility in making a choice. Lastly, the tool underwent validated assessment of decisional acceptability, decisional conflict, and decisional self‐efficacy.The decision‐aid underwent 5 iterations, resulting in a 4‐page written aid (Flesch–Kincaid reading level 6.1) explaining therapy choices, risks and benefits, providing self‐rating for attribute importance for the options and self‐assessment regarding how adequate the information was in decision‐making. A total of n = 135 caregivers of food‐allergic children assessed the decision‐aid, noting good acceptability, high decisional self‐efficacy (mean score 85.9/100) and low decisional conflict (mean score 20.9/100). Information content was rated adequate and sufficient, the therapy choices wording balanced, and presented without bias for a “best choice.” Lower decisional conflict was associated with caregiver‐reported anaphylaxis.This first pediatric OIT decision‐aid, agnostic to product, allergen, and age has good acceptability, limited bias, and is associated with low decisional conflict and high decisional self‐efficacy. It supports SDM in navigating the decision to start OIT or continue allergen avoidance. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Omalizumab (XOLAIR®)‐assisted multi‐food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab‐assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab‐assisted mOIT and desensitization outcomes has not yet been fully elucidated. In this study, due to the key roles of regulatory T (Treg) cells and the type 2 helper T cell (Th2) pathway in immune tolerance to food allergens, we aimed to characterize their association with the desensitization outcomes of omalizumab‐assisted mOIT.Mass cytometry and multiplex cytokine assays were performed on blood samples obtained from participants with allergies to peanut, cashew, or milk in our phase 2 clinical study (NCT02626611). Comprehensive statistical and bioinformatic analyses were conducted on high‐dimensional cytometry‐based single‐cell data and high‐throughput multiplex cytokine data.Our results demonstrated that the frequency of HLA‐DR+ Treg cells, and the production of Th2 cytokines (IL‐4, IL‐5, IL‐13, and IL‐9) as well as the immunoregulatory cytokine IL‐10 by peripheral blood mononuclear cells (PBMCs) was significantly increased in cultures with allergen compared to cultures with media alone at baseline (Week 0). We also observed increased frequency of allergen responsive HLA‐DR+ Treg cells and enhanced production of IL‐10 by PBMCs in participants who achieved successful desensitization compared to those with failure of desensitization. However, the production of Th2 cytokines by PBMCs did not show significant differences between participants with different desensitization outcomes (success vs. failure of desensitization), despite omalizumab‐assisted mOIT inducing a significant reduction in the production of Th2 cytokines.We demonstrated that the frequency of HLA‐DR+ Treg cells and IL‐10 cytokine production by PBMCs are associated with desensitization outcomes of omalizumab‐assisted mOIT. These findings suggest potential immunological parameters that could be targeted to enhance desensitization success rates. [ABSTRACT FROM AUTHOR]

A review of the article "Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze" by K. Hasegawa et al, which appeared in a 2019 issue of the journal "JAMA Pediatrics" is presented.

The article provides a summary of the Synopsis Book by the American Academy of Pediatrics on advances and key observations that will impact the care of children with allergic and immunologic diseases from 2016 to 2017. Topics discussed include an increase in the prevalence of allergic diseases, studies on anaphylaxis and the need for education on preparedness and management and studies on immunotherapy for food allergy.

The article discusses research on benefits associated with ondansetron related to resolution of acute food protein-induced enterocolitis syndrome (FPIES) reactions, in which discussions include treatment of acute FPIES and effectiveness of ondansetron.

An introduction to the 2014-2015 synopsis book of the Section on Allergy and Immunology journal is presented, which includes several studies on food allergies, researches on asthma and works about primary immunodeficiency.

The article presents a study that assessed the incidence of food allergies and identified risk factors for the development of food allergies in infants. Topics discussed include results showing that the most common food allergy was milk followed by egg, and the most frequent symptom during a positive food challenge was cutaneous and a review of the study.

Background Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. Objective We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. Methods In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. Results Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose ( P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions ( P = .55). There were no significant differences in allergen-specific IgE and IgG 4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. Conclusion FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used. [ABSTRACT FROM AUTHOR]

This article presents the abstract of the study Microarray Immunoassay: Association of Clinical History, In Vitro IgE Function, and Heterogeneity of Allergenic Peanut Isotopes, by W. G. Shreffler, et al, which appeared in a 2004 issue of the Journal of Allergy and Clinical Immunology. Sera from 77 peanut-allergic patients and 15 non-peanut-allergic control patients were analyzed. A set of 213 overlapping 20-residue peptides was synthesized corresponding to the primary sequences of the major peanut allergens, Ara h1, Ara h2, and Ara h3. The protein microarray immunoassay confirmed that Ara h1, Ara h2, and Ara h3 are major peanut allergens and allows for parallel epitope analysis. This has led to the discovery of an additional important epitope of Ara h1 and the recognition of a high degree of patient heterogeneity. This qualitative difference in epitope diversity might provide prognostic information about the patient.

Background Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available, and accidental ingestion can be life-threatening. Food Allergy Herbal Formula-2 (FAHF-2) blocks peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe and well tolerated in an acute phase I study of patients with food allergy. Objective We sought to assess the safety of FAHF-2 in an extended phase I clinical trial and determine the potential effects on peripheral blood basophils from patients with food allergy. Methods Patients in an open-label study received 3.3 g (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiographic data were acquired at baseline and at 2-month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated by using CCR3/CD63 staining and flow cytometry. Results Of 18 patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function study results, or electrocardiographic findings before and after treatment were found. There was a significant reduction ( P < .010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend toward a reduction in eosinophil and basophil numbers after treatment. Conclusion FAHF-2 was safe and well tolerated and had an inhibitory effects on basophil numbers in an extended phase I clinical study. A controlled phase II study is warranted. [ABSTRACT FROM AUTHOR]

Background: Results from large-scale epitope mapping with a peptide microarray have been shown to correlate with clinical features of milk allergy. Objectives: We sought to assess IgE and IgG4 epitope diversity and IgE affinity in different clinical phenotypes of milk allergy and identify informative epitopes that might be predictive of clinical outcomes of milk allergy. Methods: Forty-one subjects were recruited from a larger study on the effects of ingesting heat-denatured milk proteins in subjects with milk allergy. Using food challenges, subjects were characterized as being clinically reactive to all forms of milk (n = 17), being tolerant to heated milk (HM) products (n = 16), or having outgrown their milk allergy (n = 8). Eleven healthy volunteers without milk allergy served as control subjects. A peptide microarray was performed by using the previously published protocol. Results: Subjects with milk allergy had increased epitope diversity compared with those who outgrew their allergy. HM-tolerant subjects had IgE-binding patterns similar to those who had outgrown their allergy, but IgG4-binding patterns that were more similar to those of the allergic group. Binding to higher numbers of IgE peptides was associated with more severe allergic reactions during challenge. There was no association between IgG4 peptides and clinical features of milk allergy. Using a competitive peptide microarray assay, allergic patients demonstrated a combination of high- and low-affinity IgE binding, whereas HM-tolerant subjects and those who had outgrown their milk allergy had primarily low-affinity binding. Conclusions: Greater IgE epitope diversity and higher affinity, as determined by using the peptide microarray, were associated with clinical phenotypes and severity of milk allergy. [Copyright &y& Elsevier]

An abstract of the article "In Vitro and In Vivo Cross-reactivity Studies of Legume Allergy in a Mediterranean Population," by M. Martínez San Ireneo, M. D. Ibáñez, E. Fernández-Caldas and J. Carnés is presented.

Background: The peptide microarray is a novel assay that facilitates high-throughput screening of peptides with a small quantity of sample. Objective: We sought to use overlapping peptides of milk allergenic proteins as a model system to establish a reliable and sensitive peptide microarray-based immunoassay for large-scale epitope mapping of food allergens. Methods: A milk peptide microarray was developed by using commercially synthesized peptides (20-mers, 3 offset) covering the primary sequences of αs1-casein, αs2-casein, β-casein, κ-casein, and β-lactoglobulin. Conditions for printing and immunolabeling were optimized using a serum pool of 5 patients with milk allergy. Reproducibility of the milk peptide microarray was evaluated using replicate arrays immunolabeled with the serum pool, whereas specificity and sensitivity were assessed by using serial dilution of the serum pool and a peptide inhibition assay. Results: Our results show that epitopes identified by the peptide microarray were mostly consistent with those identified previously by SPOT membrane technology, but with specific binding to a few newly identified epitopes of milk allergens. Data from replicate arrays were reproducible (r ≥ 0.92) regardless of printing lots, immunolabeling, and serum pool batches. Using the serially diluted serum pool, we confirmed that IgE antibody binding detected in the array was specific. Peptide inhibition of IgE binding to the same peptide and overlapping peptides further confirmed the specificity of the array. Conclusion: A reliable peptide microarray was established for large-scale IgE epitope mapping of milk allergens, and this robust technology could be applied for epitope mapping of other food allergens. [Copyright &y& Elsevier]

The article discusses research being done on the use of atopy patch test (ATP) in the diagnosis of food protein-induced enterocolitis syndrome (FPIES). It references a study by T. A. Brown-Whitehorn et al, published in the 2006 issue of "Pediatric Allergy and Immunology." The study aimed to determine if ATP is able to predict the results of the oral food challenge (OFC) for FPIES. The study concluded that APT seems to be a promising diagnostic tool for the diagnosis of FPIES. The reviewer commented that the results of the study suggest that APT may have some utility in guiding the diagnosis and management of FPIES.

This article presents an abstract of the study Determination of Food Specific IgE Levels Over Time Can Predict the Development of Tolerance in Cow's Milk and Hen's Egg Allergy, by L. P. Shek, et al, which appeared in a 2004 issue of the Journal of Allergy and Clinical Immunology. Eighty-eight patients with hen's egg allergy and 49 patients with cow's milk allergy who underwent repeated double-blind placebo-controlled food challenges were included in the study. The rate of decrease in food specific immunoglobulin E levels over time was predictive for the likelihood of developing tolerance in milk and egg allergy. This study's use of likelihood estimates could aid clinicians in providing prognostic information and in the timing of subsequent food challenges, thereby decreasing the number of premature and unnecessary double-blind placebo-controlled food challenges.

Background: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.Methods: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.Findings: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.Interpretation: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.Funding: National Institute of Allergy and Infectious Disease, Immune Tolerance Network. [ABSTRACT FROM AUTHOR]