The Relationship Between Eosinophilic Esophagitis and Immunotherapy.

Immunotherapy is a treatment approach based on the principle of incremental allergen exposure to achieve desensitization. Recently, oral immunotherapy has been introduced as a treatment of IgE-mediated food allergy. Some patients receiving oral immunotherapy for food allergy may develop eosinophilic esophagitis. Here, we summarize the literature examining this association, its treatment, and outcomes and discuss possible explanations for this clinical phenomenon. We further identify potential associations with aeroallergen sensitivity and other forms of immunotherapy including subcutaneous immunotherapy and sublingual immunotherapy. Finally, we discuss management of immunotherapy-induced eosinophilic esophagitis. Epicutaneous immunotherapy is highlighted as an area of therapeutic investigation.

Role of biologics in severe food allergy.

PURPOSE OF REVIEW: This review examine the dynamic landscape of food allergy treatment within the context of emerging biologics. Our purpose is to comprehensively evaluate the potential benefits, challenges, and transformative impact associated with the utilization of biologics in comparison to conventional therapeutic modalities. RECENT FINDINGS: This document synthesizes recent scientific investigations to various biologics, such as omalizumab, ligelizumab, dupilumab, and tezepelumab, providing a nuanced understanding of their roles in oral immunotherapy, rapid desensitization, and overall food allergy management. Recent studies and clinical trials highlight the impact of anti-IgE treatment on food allergies, revealing critical findings such as dose-related efficacy, facilitation of rapid desensitization in peanut allergies, and the sustained positive outcomes observed in individuals with multifood allergies. SUMMARY: The use of biologics presents a groundbreaking approach in the treatment of food allergies. The multifaceted action of these agents, along with their potential to overcome the challenges associated with traditional therapies, marks a significant advancement. Despite the persisting challenges of economic constraints and the need for further safety studies, biologics offer a promising avenue for improving the quality of life for individuals with food allergies. Ongoing research and collaborative efforts are imperative to fully realize the transformative potential inherent in these emerging therapeutic frontiers.

New biologics for food allergy.

PURPOSE OF REVIEW: This review aims to explore role of emerging biologics, including ligelizumab, UB-221, dupilumab, and antialarmins, in food allergy management. With a focus on recent developments, we evaluate their promise in mitigating adverse events during oral immunotherapy (OIT), reducing allergic reactions, and addressing the limitations of current therapeutic options. RECENT FINDINGS: Antiimmunoglobulin E mAbs, exemplified by omalizumab, demonstrate efficacy in desensitization and safety improvement during multiallergen OIT. Next-generation antibodies like ligelizumab and UB-221 exhibit enhanced potency and unique mechanisms, holding promise for food allergy treatment. Dupilumab, targeting IL-4 receptor alpha, presents potential benefits in decreasing allergen-specific IgE and modifying the atopic march. Exploration of antialarmins, specifically anti-IL-33 (etokimab) and anti-TSLP (tezepelumab), reveals encouraging results, with etokimab showing early success in peanut allergy trials. SUMMARY: Biologics hold promising potential for food allergy treatment. Tailoring therapeutic approaches based on shared decision-making becomes pivotal. While omalizumab remains a significant option, next-generation anti-IgE antibodies and agents targeting alarmins exhibit unique strengths. Dupilumab, despite limited success as monotherapy, shows promise as an adjunct for OIT. Careful consideration of treatment goals, patient preferences, and the evolving landscape of biologics will shape future clinical practice, offering allergists an expanded toolbox for personalized food allergy management.

Vegetable Extracts as Therapeutic Agents: A Comprehensive Exploration of Anti-Allergic Effects.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

A randomized, double-blind placebo-controlled study on the efficacy of Omalizumab on food allergy threshold in children with severe food allergy.

BACKGROUND: Food allergy is common in childhood with some children having a low threshold and being difficult to protect from accidental ingestion of the offending food. Therapies for this potentially life-threatening condition are highly needed. The aim of this study was to evaluate the efficacy of Omalizumab in food-allergic children. METHODS: This is a single-center, double-blind, placebo-controlled study. Food allergic children with a cumulative threshold ≤443 mg food protein at DBPCFC were randomized to Omalizumab (asthma dose) or placebo (3:1). After 3 months, a second DBPCFC was performed (steps 3, 10, 30, 100, 300, 1000, and 3000 mg food protein), followed by a separate open challenge up to 10,000 and 30,000 mg food protein if negative. Responders were defined as ≥2-step increases in threshold. Non-responders received high-dose Omalizumab. A third DBPCFC was performed after 6 months. Skin testing, blood samples, and the severity of atopic co-morbidity were registered during the study and 3 months after treatment. RESULTS: In total, 20 children were evaluated at 3 months (14 Omalizumab, 6 placebo). All treated with Omalizumab increased their threshold at least two steps and with a significant difference between the Omalizumab and the placebo group (p = .003), although the intended number of included children was not reached. The threshold before Omalizumab treatment was 13-443 mg food protein while the threshold after 3 months of treatment increased up to 44,000 mg (1143-44,000). In the placebo group, two children improved threshold during the study. CONCLUSION: An increase in the threshold level during Omalizumab treatment significantly improve patient safety and protected all children against small amount of allergen.

Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Applying Artificial Intelligence to Identify Common Targets for Treatment of Asthma, Eczema, and Food Allergy.

INTRODUCTION: Allergic disorders are common diseases marked by the abnormal immune response toward foreign antigens that are not pathogens. Often patients with food allergy also suffer from asthma and eczema. Given the similarities of these diseases and a shortage of effective treatments, developing novel therapeutics against common targets of multiple allergies would offer an efficient and cost-effective treatment for patients. METHODS: We employed the artificial intelligence-driven target discovery platform, PandaOmics, to identify common targets for treating asthma, eczema, and food allergy. Thirty-two case-control comparisons were generated from 15, 11, and 6 transcriptomics datasets related to asthma (558 cases, 315 controls), eczema (441 cases, 371 controls), and food allergy (208 cases, 106 controls), respectively, and allocated into three meta-analyses for target identification. Top-100 high-confidence targets and Top-100 novel targets were prioritized by PandaOmics for each allergic disease. RESULTS: Six common high-confidence targets (i.e., IL4R, IL5, JAK1, JAK2, JAK3, and NR3C1) across all three allergic diseases have approved drugs for treating asthma and eczema. Based on the targets' dysregulated expression profiles and their mechanism of action in allergic diseases, three potential therapeutic targets were proposed. IL5 was selected as a high-confidence target due to its strong involvement in allergies. PTAFR was identified for drug repurposing, while RNF19B was selected as a novel target for therapeutic innovation. Analysis of the dysregulated pathways commonly identified across asthma, eczema, and food allergy revealed the well-characterized disease signature and novel biological processes that may underlie the pathophysiology of allergies. CONCLUSION: Altogether, our study dissects the shared pathophysiology of allergic disorders and reveals the power of artificial intelligence in the exploration of novel therapeutic targets.

Factors Associated With Epinephrine Use in the Treatment of Anaphylaxis in Infants and Toddlers.

BACKGROUND: Undertreatment of anaphylaxis with epinephrine continues to be an unmet need and is a particular challenge among infants and toddlers. OBJECTIVE: To address this gap by identifying barriers and solutions to appropriate and timely administration of epinephrine. METHODS: We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when younger than 36 months. Outcomes of interest included epinephrine use in community and health care settings to treat probable anaphylaxis. RESULTS: Of 264 probable anaphylaxis cases, 39% of infants (aged <12 months) and 61% of toddlers (aged 12-35 months) received epinephrine at any time during the child's most severe allergic reaction (P = .001). A previous diagnosis of a food allergy was reported in 62% of cases where epinephrine was used compared with 26% of cases where epinephrine was not used (P < .001). In children with a previous diagnosis of a food allergy, epinephrine was used in 89% of those who were prescribed an anaphylaxis action plan compared with 50% of those without a plan (P = .001). The adjusted odds ratio for the association between having an anaphylaxis action plan and epinephrine use in cases of probable anaphylaxis was 5.39 (95% confidence interval, 2.18-13.30). CONCLUSIONS: Epinephrine use at any time (including in health care settings) during probable anaphylaxis is more likely in infants and toddlers with a previously diagnosed food allergy than those without diagnosis. The provision of an anaphylaxis action plan is also associated with increased epinephrine use during probable anaphylaxis in this population.

Food oral immunotherapy: Any distinguishing factors predicting the need of anti-IgE?

Oral immunotherapy (OIT) has gained popularity recently for IgE-mediated food allergy. Omalizumab (OMZ) has been used in patients (10-20%) who have too severe/frequent allergic reactions (AR) to continue OIT, to reduce these reactions. In this study, it was aimed to compare two groups of patients who completed OIT with and without OMZ and to seek determinants predicting the need of this treatment. It was also aimed to share the clinical findings regarding the long-term use of OMZ and the withdrawal process. Forty-one patients were started OIT and 93% could be desensitized. Two groups were similar in means of demographic characteristics, and clinical and laboratory findings. The patients who needed OMZ during OIT had also lower reaction doses during oral challenge (p = 0.037). Higher AR rate in this group declined after starting OMZ (p < 0.001). The injection intervals of OMZ were gradually extended. Most patients were able to discontinue OMZ (81%). There were no severe reactions during drug withdrawal attempts. The low reaction thresholds during oral food challenge may give a clue about OMZ requirement during OIT. It may be an option to start the treatment before OIT if reaction was seen in the first few steps of the oral food challenge. For the sake of safety, extension of injection intervals should be preferred instead of abruptly stopping OMZ.

Dietary Polyphenols-Natural Bioactive Compounds with Potential for Preventing and Treating Some Allergic Conditions.

In light of the constantly increasing prevalence of allergic diseases, changes in dietary patterns have been suggested as a plausible environmental explanation for the development and progression of these diseases. Nowadays, much attention has been paid to the development of dietary interventions using natural substances with anti-allergy activities. In this respect, dietary polyphenols have been studied extensively as one of the most prominent natural bioactive compounds with well-documented anti-inflammatory, antioxidant, and immunomodulatory properties. This review aims to discuss the mechanisms underlying the potential anti-allergic actions of polyphenols related to their ability to reduce protein allergenicity, regulate immune response, and gut microbiome modification; however, these issues need to be elucidated in detail. This paper reviews the current evidence from experimental and clinical studies confirming that various polyphenols such as quercetin, curcumin, resveratrol, catechins, and many others could attenuate allergic inflammation, alleviate the symptoms of food allergy, asthma, and allergic rhinitis, and prevent the development of allergic immune response. Conclusively, dietary polyphenols are endowed with great anti-allergic potential and therefore could be used either for preventive approaches or therapeutic interventions in relation to allergic diseases. Limitations in studying and widespread use of polyphenols as well as future research directions are also discussed.

2'-Fucosyllactose alleviates OVA-induced food allergy in mice by ameliorating intestinal microecology and regulating the imbalance of Th2/Th1 proportion.

Food allergy (FA) has become a prominent problem in public health. 2'-Fucosyllactose (2'-FL) was reported to alleviate FA symptoms; however, the regulatory mechanism is still unclear. This study evaluated the 2'-FL antiallergic potential in an ovalbumin (OVA)-sensitized mouse model and explored the systemic effects of 2'-FL on gut microecology and the intestinal immune barrier. The results showed that 2'-FL alleviated allergy symptoms, decreased serum allergic indicator levels, enhanced the intestinal barrier, and attenuated low-grade inflammation. The up-regulation of G protein-coupled receptors (GPRs) was associated with higher levels of short-chain fatty acids (SCFAs) in 2'-FL intervention mice. 2'-FL also improved the intestinal microbiota diversity and increased the abundance of Akkermansia, Lachnospiraceae UCG-006, and Ruminococcaceae while suppressing Muribaculaceae, Desulfovibrionaceae, and Erysipelotrichaceae. Additionally, 2'-FL ameliorated the imbalance of Th2/Th1, mainly by decreasing Th2-type immune response and enhanced CD4 + Foxp3 + Treg immunoreaction. These results suggest that 2'-FL restores intestinal barrier defects, gut microbiota disorder, and immune impairment while alleviating ovalbumin-induced allergic symptoms in FA mice.

Alergia alimentaria: importancia de los cofactores / Food allergy: the importance of cofactors

Las LTP (lipid transfer proteins) son una familia de proteínas presentes en diferentes alimentos. La sintomatología de la alergia a las LTP es muy variable, desde clínica leve hasta sistémica, en ocasiones, presentando síntomas únicamente en presencia de cofactores. Se presenta el caso de una paciente de 11 años que acude a urgencias con clínica de anafilaxia tras ingesta previa de fruta mientras realizaba ejercicio físico, destacando la importancia de la historia clínica y la sospecha diagnóstica en el enfoque de esta entidad (AU)

LTP (lipid transfer proteins) are a family of proteins present in different foods. The symptomatology of allergy to LTP is highly variable, ranging from mild to systemic. Sometimes, symptoms are only present in the presence of cofactors.We present the case of an 11-year-old female patient who presented to the emergency department with anaphylaxis following previous ingestion of fruit while doing physical exercise, highlighting the importance of the clinical history and diagnostic suspicion in the approach to this entity. (AU)

Lycopene alleviates food allergy by modulating the PI3K/AKT pathway in peanut-sensitized BALB/c mice.

Food allergies, which lead to life-threatening acute symptoms, are considered an important public health problem. Therefore, it is essential to develop efficient preventive and treatment measures. We developed a crude peanut protein extract (PPE)-induced allergy mouse model to investigate the effects of lycopene on peanut allergy. Mice were divided into four groups: 5 mg/kg lycopene, 20 mg/kg lycopene, no treatment, and control groups. Serum inflammatory factors were detected using enzyme-linked immunosorbent assay. In addition, pathology and immunohistochemistry analyses were used to examine the small intestine of mice. We found that lycopene decreased PPE-specific immunoglobulin E (IgE) and IL-13 levels in the serum, relieved small intestine inflammation, attenuated the production of histamine and mouse mast cell protease-1, and downregulated PI3K and AKT1 expression in the small intestine tissues of mice allergic to peanuts. Our results suggest that lycopene can ameliorate allergy by attenuating the PI3K/AKT pathway and the anaphylactic reactions mediated by PPE-specific IgE.