Treatment Of Food Allergy Research Articles

A synbiotic of Anaerostipes caccae and lactulose prevents and treats food allergy in mice

Depletion of beneficial microbes by modern lifestyle factors correlates with the rising prevalence of food allergies. Re-introduction of allergy-protective bacteria may be an effective treatment strategy. We characterized the fecal microbiota of healthy and food-allergic infants and found that the anaerobe Anaerostipes caccae (A.caccae) was representative of the protective capacity of the healthy microbiota. We isolated a strain of A.caccae from the feces of a healthy infant and identified lactulose as a prebiotic to optimize butyrate production by A.caccae invitro. Administration of a synbiotic composed of our isolated A.caccae strain and lactulose increased luminal butyrate in gnotobiotic mice colonized with feces from an allergic infant and in antibiotic-treated specific pathogen-free (SPF) mice, and prevented or treated an anaphylactic response to allergen challenge. The synbiotic's efficacy in two models and microbial contexts suggests that it may be a promising approach for the treatment of food allergy.

Allergen-specific IgA and IgG antibodies as inhibitors of mast cell function in food allergy.

Food allergy, a group of adverse immune responses to normally innocuous food protein antigens, is an increasingly prevalent public health issue. The most common form is IgE-mediated food allergy in which food antigen-induced crosslinking of the high-affinity IgE-receptor, FcεRI, on the surface of mast cells triggers the release of inflammatory mediators that contribute to a wide range of clinical manifestations, including systemic anaphylaxis. Mast cells also play a critical function in adaptive immunity to foods, acting as adjuvants for food-antigen driven Th2 cell responses. While the diagnosis and treatment of food allergy has improved in recent years, no curative treatments are currently available. However, there is emerging evidence to suggest that both allergen-specific IgA and IgG antibodies can counter the activating effects of IgE antibodies on mast cells. Most notably, both antigen-specific IgA and IgG antibodies are induced in the course of oral immunotherapy. In this review, we highlight the role of mast cells in food allergy, both as inducers of immediate hypersensitivity reactions and as adjuvants for type 2 adaptive immune responses. Furthermore, we summarize current understanding of the immunomodulatory effects of antigen-specific IgA and IgG antibodies on IgE-induced mast cell activation and effector function. A more comprehensive understanding of the regulatory role of IgA and IgG in food allergy may provide insights into physiologic regulation of immune responses to ingested antigens and could seed novel strategies to treat allergic disease.

Omalizumab: A Novel Treatment for Multiple Food Allergies

Omalizumab: A Novel Treatment for Multiple Food Allergies

Genetic Mechanism of Food Allergies

Food allergy (FA) is the culmination of different genetic and environmental factors. It is an increasingly concerning health problem affecting millions of people around the globe. Currently, there is research being done on the impact that genetics have on a person’s likelihood of having a food allergy, as well as how genetics research can further help the prevention and treatment of food allergies. This paper aims to review current genetic studies, such as familial aggregation studies and candidate gene association studies, both of which provide evidence that certain genes make it more likely for people to have FA. Some genes including the HLA gene family linked to peanut and apple allergies, the CD14 gene linked to multiple FA studies, and SPINK5, a protease inhibitor protein, all make a person with any of these genes more likely to have FA. This paper also focuses on examining future treatments, specifically immunotherapy treatments like the OIT, and future diagnostic tests for FA, such as the BAT and CRD, all of which are now being tested in labs. The field of FA genetics is a new and promising area of study and has the potential to impact many lives in the future.

New evidence in food allergies treatment.

To acknowledge, the newly available treatments for food allergy described in the latest scientific literature, such as oral immunotherapy (OIT), biologics and the combination of them in managing patients with IgE-mediated food allergies. Recent studies suggest that OIT and biologics, alone or together, can have a role as disease-modifying treatments for food allergies. The FDA has recently approved omalizumab as a treatment for food allergy. Other biologics are currently under evaluation and further studies are needed to assess the efficacy and safety of these therapies. The allergology scenario is rapidly evolving, the recent introduction and approval of new therapeutic strategies such as biotechnological drugs and allergen immunotherapy is changing the therapeutic paradigm: we are witnessing a shift from a strategy based on avoiding the trigger and reversing an allergic reaction already in progress, to one that aims to modify the natural history of the disease by acting on the immunological mechanisms that determine it. This approach is consistent with the modern perspective of a personalized patient-tailored medicine. In this opinion review, we will provide a brief analysis of current and future therapeutic options for IgE-mediated food allergy, focusing on OIT, biologics and their combination.

Nutritional and Psychosocial Impact of Food Allergy in Pediatric Age.

Treatment of IgE-mediated food allergy involves avoiding the food causing the allergic reaction. In association, an action plan for allergic reactions is indicated, sometimes including self-injectable adrenaline. In addition to these dietary and medical implications, there are two equally important ones: nutritional and psychosocial. From a nutritional point of view, it is known that children suffering from food allergy have a growth delay in height and weight compared to their non-allergic peers. Specifically, this condition is directly related to the specific food excluded from the diet, the number of foods excluded and the duration of the elimination diet. From a psychosocial point of view, the child often cannot eat the foods other guests eat. Children with food allergy may perceive an aura of parental anxiety around their mealtime and may be afraid that what they eat could have harmful consequences for their health. Furthermore, children's and their parents' quality of life appears to be affected. The need to manage the allergy and the nutritional and psychosocial problems positions the pediatric nutritionist and the child neuropsychiatrist as support figures for the pediatric allergist in managing the child with food allergy.

Omalizumab for the reduction of allergic reactions to foods: a narrative review.

The frequency of food allergies varies between 2% and 10%, depending on characteristics including age, region, race, and method of diagnosis self-reported by patients or oral food challenges (OFCs). The most common allergies reported are tree nuts (1.2%), milk (1.9%), peanuts (2.2%), and shellfish (1.3%). Omalizumab injection has now been approved by the FDA for the treatment of immunoglobulin E-mediated food allergies in specific adults and children aged one year or older. This medication reduces the risk of allergic reactions (Type I), which can include anaphylaxis, when an individual accidentally encounters one or more food allergens. Omalizumab functions by binding to IgE and altering IgE-mediated pathways, which lessens IgE's capacity to cause allergic reactions. Promising outcomes from clinical trials and case studies include lowered anaphylactic risk and enhanced tolerance to allergens. Omalizumab, however, may have adverse effects; thus, close observation is required. Overall, this review sheds light on the efficacy, safety, and clinical implications of omalizumab, highlighting its potential as a useful intervention for IgE-mediated food allergies.

Fermented Gracilaria lemaneiformis polysaccharides alleviate food allergy by regulating Treg cells and gut microbiota

Food allergy has a significant impact on the health and well-being of individuals, affecting both their physical and mental states. Research on natural bioactive compounds, such as polysaccharides extracted from seaweeds, holds great promise in the treatment of food allergies. In this study, fermented Gracilaria lemaneiformis polysaccharides (F-GLSP) were prepared using probiotic fermentation. Probiotic fermentation of Gracilaria lemaneiformis reduces the particle size of polysaccharides. To compare the anti-allergic activity of F-GLSP with unfermented Gracilaria lemaneiformis polysaccharides (UF-GLSP), an OVA-induced mouse food allergy model was established. F-GLSP exhibited a significant reduction in OVA-specific IgE and mMCP levels in allergic mice. Moreover, it significantly inhibited Th2 differentiation and IL-4 production and significantly promoted Treg differentiation and IL-10 production in allergic mice. In contrast, UF-GLSP only reduced OVA-specific IgE and mMCP in the serum of allergic mice. Furthermore, F-GLSP demonstrated a more pronounced regulation of intestinal flora abundance compared to UF-GLSP, significantly influencing the populations of Firmicutes, Bacteroidetes, Lactobacillus, and Clostridiales in the intestines of mice with food allergy. These findings suggest that F-GLSP may regulate food allergies in mice through multiple pathways. In summary, this study has promoted further development of functional foods with anti-allergic properties based on red algae polysaccharides.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

Racial and Socioeconomic Disparities Exist in Patients Pursuing Peanut Oral Immunotherapy

BackgroundOral immunotherapy (OIT) is a promising treatment for food allergy. Prior studies demonstrate significant differences among food allergic individuals across race, ethnicity, and socioeconomic groups. Disparities in OIT have not been evaluated. ObjectiveWe assessed disparities in the use of OIT in patients with peanut allergy based on race, ethnicity, and socioeconomic status at a single academic medical center. MethodsWe identified 1028 peanut allergic patients under 18 years of age receiving care in the University of Michigan food allergy clinics. 148 patients undergoing peanut OIT (treatment group) were compared to the 880 patients avoiding peanut (control group). Pertinent demographic and socioeconomic characteristics were compared. ResultsThere were no differences in gender or ethnicity between the OIT and control groups. However, Black patients comprised 18% of the control group but only 4.1% of the OIT treatment group (p<0.0001). The proportion of patients with private insurance was significantly higher in the treatment group compared to control group, 93.2% vs 82.2% (p=0.0004). Finally, the Neighborhood Affluence Index, a Census-based measure of the relative socioeconomic prosperity of a neighborhood, was significantly higher in the OIT group vs. the control group (0.51±0.18 vs 0.47±0.19) (p=0.015), while the Neighborhood Disadvantage Index, a Census-based measure of the relative socioeconomic disadvantage of a neighborhood, was significantly lower (0.082±0.062 vs 0.10±0.093) (p=0.020). ConclusionSignificant racial and economic disparities exist at our institution between peanut allergic individuals who receive OIT and those who do not. Efforts to understand the basis for these disparities are important to ensure patients have equitable access to OIT.

Differences in the Course, Diagnosis, and Treatment of Food Allergies Depending on Age-Comparison of Children and Adults.

Food allergy (FA) has become a common global public health issue, with a growing prevalence in the modern world and a significant impact on the lives of patients, their families, and caregivers. It affects every area of life and is associated with elevated costs. Food allergy is an adverse immune reaction that occurs in response to a given food. The symptoms vary from mild to severe and can lead to anaphylaxis. This is why it is important to focus on the factors influencing the occurrence of food allergies, specific diagnostic methods, effective therapies, and especially prevention. Recently, many guidelines have emphasized the impact of introducing specific foods into a child's diet at an early age in order to prevent food allergies. Childhood allergies vary with age. In infants, the most common allergy is to cow's milk. Later in life, peanut allergy is more frequently diagnosed. Numerous common childhood allergies can be outgrown by adulthood. Adults can also develop new IgE-mediated FA. The gold standard for diagnosis is the oral provocation test. Skin prick tests, specific IgE measurements, and component-resolved diagnostic techniques are helpful in the diagnosis. Multiple different approaches are being tried as possible treatments, such as immunotherapy or monoclonal antibodies. This article focuses on the prevention and quality of life of allergic patients. This article aims to systematize the latest knowledge and highlight the differences between food allergies in pediatric and adult populations.

The hype and hope of new food allergy treatments.

The hype and hope of new food allergy treatments.

Modification of structure, epitope and allergenicity on heat-stressed ovalbumin by resveratrol

Allergen modification is a novel strategy for preventing and treating food allergy. Resveratrol (RES) can be used as a modifying ligand for allergens, but the interaction mechanism between RES and allergens is still not detailed, and the ramifications of this interaction on the structure, epitope and allergenicity of allergens are also lacking a clear explanation. In addition, the application of heat can promote protein structure to unfold and expose more binding sites to facilitate interaction. Therefore, in this study, ovalbumin (OVA) was selected as the allergen model and was heated to expose more binding sites. The effects of the interaction between RES and heat-stressed ovalbumin (HOVA) on allergen structure, epitope and allergenicity were investigated by combining routine experimental analysis and computer simulation. Results showed heat stress at 323 K for 15 min could better unfold the molecular structure of OVA. On this basis, the interaction between RES and OVA was strengthened, which showed a static quenching of the ground state complex with binding affinity of 1.25 × 106 L/mol. The binding of RES induced the variation of protein microenvironment, and the overall structure tended to disordered direction. Computer simulation had shown RES could directly act on the IgE epitope region (AA251-260) of the OVA. The allergenicity evaluation experiment further indicated the combination of RES alleviated the IgE binding capacity of HOVA. These findings are helpful to further study the mechanism of RES ligand modification to change food allergy.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent

Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Targeting inhibitory Siglec-3 to suppress IgE-mediated human basophil degranulation

BackgroundSiglec-3 (CD33) is a major Siglec expressed on human mast cells and basophils and engagement of CD33 leads to inhibition of cellular signaling via immunoreceptor tyrosine-based inhibitory motifs (ITIMs). ObjectiveWe sought to inhibit human basophil degranulation by simultaneously recruiting inhibitory CD33 to the IgE-FcεRI complex using monoclonal anti-IgE directly conjugated to CD33 ligand (CD33L). MethodsDirect and indirect basophil activation tests (BAT) were used to assess both antigen-specific (peanut) and antigen non-specific (polyclonal anti-IgE) stimulation. Whole blood from allergic donors was used for direct BAT, whereas non-food allergic donor blood was passively sensitized with peanut-allergic plasma in the indirect BAT. Blood was incubated with anti-IgE-CD33L or controls for one hour or overnight, then stimulated with peanut, polyclonal anti-IgE, or N-formylmethionyl-leucyl-phenylalanine (fMLP) for 30 minutes. Degranulation was determined by measuring CD63 expression on the basophil surface by flow cytometry. ResultsIncubation for one hour with anti-IgE-CD33L significantly reduced basophil degranulation after both allergen-induced (peanut) and polyclonal anti-IgE stimulation, with further suppression after overnight incubation with anti-IgE-CD33L. As expected, anti-IgE-CD33L did not block basophil degranulation due to fMLP, providing evidence that this inhibition is IgE-pathway specific. Finally, CD33L is necessary for this suppression, as monoclonal anti-IgE without CD33L was unable to reduce basophil degranulation. ConclusionsPre-treating human basophils with anti-IgE-CD33L significantly suppressed basophil degranulation through the IgE-FcεRI complex. The ability to abrogate IgE-mediated basophil degranulation is of particular interest, as treatment with anti-IgE-CD33L prior to antigen exposure could have broad implications for the treatment of food, drug, and environmental allergies.

New biologics for food allergy.

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. 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. 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.

Role of biologics in severe food allergy.

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. 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. 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.

Omalizumab for the Treatment of Multiple Food Allergies

BackgroundFood allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.MethodsIn 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.ResultsOf 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.ConclusionsIn 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.)

The Immunobiology and Treatment of Food Allergy.

IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper Tcell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several host-related and environmental factors impacting the risk of IgE-FA development have been identified. Mounting evidence supports the role of an impaired epithelial barrier in the development of IgE-FA, with exposure of allergens through damaged skin and gut epithelium leading to the aberrant production of alarmins and activation of TH2-type allergic inflammation. The treatment of IgE-FA has historically been avoidance with acute management of allergic reactions, but advances in allergen-specific immunotherapy and the development of biologics and other novel therapeutics are rapidly changing the landscape of food allergy treatment. Here, we discuss the pathogenesis and immunobiology of IgE-FA in addition to its diagnosis, prognosis, and treatment. Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Current and Future Treatment of Food Allergies

Food allergy prevalence is rapidly growing among school-age children in the United States, posing a significant health concern in school settings. This article aims to provide an overview of the current state of food allergy treatment options, emergency food allergy care plans, and using epinephrine autoinjectors. In addition, it explores potential future treatment options, including immunotherapy and novel therapeutic approaches. This article emphasizes the crucial role of school nurses in recognizing the treatment options currently available to students and their families, as well as fostering a safe environment for students with food allergies.