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Wheat gluten is responsible for the unique baking properties of wheat flour, but it also causes wheat-related disorders in predisposed individuals. Different commercially available gluten materials are commonly used for a variety of assays, but a detailed characterization of their composition is missing in many cases. This is why we aimed to provide an in-depth analysis of three commonly used gliadin and gluten materials from two different batches using gel electrophoretic and chromatographic techniques. The gliadin material did not show the typical qualitative and quantitative protein composition and does not appear to be representative of wheat gliadin. The two gluten materials had the expected protein composition, but both showed large batch-to-batch variability regarding total protein content. Since these variations result in different biochemical, immunological, and functional behaviors, it is important to analyze at least the total protein content of each material and each batch. [ABSTRACT FROM AUTHOR]

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Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed. [ABSTRACT FROM AUTHOR]

Background: Wheat allergy (WA), characterized by immunological responses to wheat proteins, is a gluten-related disorder that has become increasingly recognized in recent years. Bibliometrics involves the quantitative assessment of publications within a specific academic domain. Objectives: We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy. Methods: We searched the Web of Science database on 5th Dec 2023. We used the KEYWORDS: "wheat allergy or wheat anaphylaxis or wheat hypersensitivity," "gliadin allergy or gliadin anaphylaxis or gliadin hypersensitivity," "wheatdependent exercise-induced anaphylaxis," and "baker's asthma" for our search. All items published between 1993 and 2023 were included. The top 100 most cited articles were identified and analyzed. Results: Our study conducted an in-depth bibliometric analysis of the 100 mostcited articles in the field of wheat allergy, published between 2002 and 2019. These articles originated from 20 different countries, predominantly Japan and Germany. The majority of these articles were centered on the pathogenesis and treatment of wheat allergy (WA). The Journal of Allergy and Clinical Immunology (JACI) was the most prolific contributor to this list, publishing 14 articles. The article with the highest citation count was published by Biomed Central (BMC) and garnered 748 citations. The peak citation year was 2015, with a total of 774 citations, while the years 1998, 2001, and 2005 saw the highest publication frequency, each with 7 articles. Conclusion: Our study aims to provide physicians and researchers with a historical perspective for the scientific progress of wheat allergy, and help clinicians effectively obtain useful articles that have a significant impact on the field of wheat allergy. [ABSTRACT FROM AUTHOR]

Le gluten est une protéine contenue dans différentes céréales comme le blé, le seigle et l'orge. La partie toxique de cette protéine est la gliadine. Chez certains individus génétiquement prédisposés porteurs des allèles HLA DQ2 et/ou DQ8, la gliadine va déclencher une réponse immunitaire anormale à l'origine de maladie cœliaque. La maladie cœliaque est une maladie auto-immune diagnostiquée en présence d'auto-anticorps spécifiques et d'anomalies histologiques duodénales. Il existe d'autres pathologies liées à la consommation de gluten comme l'allergie au blé et l'hypersensibilité au gluten non cœliaque. L'allergie au blé est une entité bien définie avec un mécanisme IgE dépendant, des tests diagnostiques (IgE anti-blé et prick-tests) et une prise en charge connus. Par contre, l'hypersensibilité au gluten non cœliaque est une entité d'identification plus récente, rapportée souvent par les patients en raison de leurs symptômes, sans test diagnostique spécifique ; des experts ont proposé un challenge gluten versus placebo afin de préciser les personnes dont les troubles intestinaux et extra-intestinaux pourraient être améliorés par une alimentation sans gluten (ASG). Une ASG est indiquée dans la maladie cœliaque, à vie. Dans l'allergie au blé, elle est stricte mais l'allergie disparaît souvent chez l'enfant d'âge scolaire, permettant une réintroduction. Pour l'hypersensibilité au gluten non cœliaque, cette alimentation pourrait être moins stricte et transitoire. L'ASG et/ou sans caséine est parfois réalisée chez des personnes ayant des troubles du spectre autistique (TSA). Elle pourrait être efficace pour certains d'entre eux, mais elle n'est pas à recommander pour toutes les personnes ayant un TSA. Gluten is a protein contained in various cereals such as wheat, rye and barley. The toxic part of this protein is gliadin. In genetically predisposed individuals carrying HLA DQ2 and/or DQ8 alleles, gliadin will trigger an abnormal immune response that will cause celiac disease. Celiac disease is an autoimmune disease characterized by specific autoantibodies and duodenal histological abnormalities. There are other diseases related to gluten consumption such as wheat allergy and celiac gluten hypersensitivity. Wheat allergy is a well-known entity with a dependent IgE mechanism, with specific diagnostic tests (anti-wheat IgE and prick-tests) and management. In contrast, non-celiac gluten hypersensitivity was more recently identified, and often reported by patients, without specific diagnostic test; experts have proposed a gluten versus placebo challenge to identify people whose intestinal and extra-intestinal disorders could be improved by a gluten-free diet (GFD). A GFD is of course indicated in celiac disease, for life. For wheat allergy, GFD is strict but the allergy often disappears in school-aged children, allowing a gluten reintroduction. For non-celiac gluten hypersensitivity, GFD may be less strict and transient. GFD and/or casein-free diet is sometimes performed in people with autism spectrum disorders (ASD). It may be effective for some of them, but it is not recommended for all people with ASD. [ABSTRACT FROM AUTHOR]

Wheat gluten is responsible for the unique baking properties of wheat flour, but it also causes wheat-related disorders in predisposed individuals. Different commercially available gluten materials are commonly used for a variety of assays, but a detailed characterization of their composition is missing in many cases. This is why we aimed to provide an in-depth analysis of three commonly used gliadin and gluten materials from two different batches using gel electrophoretic and chromatographic techniques. The gliadin material did not show the typical qualitative and quantitative protein composition and does not appear to be representative of wheat gliadin. The two gluten materials had the expected protein composition, but both showed large batch-to-batch variability regarding total protein content. Since these variations result in different biochemical, immunological, and functional behaviors, it is important to analyze at least the total protein content of each material and each batch.

Wheat is one of the three major staple foods in the world. Although wheat is highly nutritional, it has a variety of allergenic components that are potentially fatal to humans and pose a significant hazard to the growth and consumption of wheat. Wheat allergy is a serious health problem, which is becoming more and more prevalent all over the world. To address and prevent related health risks, it is crucial to establish precise and sensitive detection and analytical methods as well as an understanding of the structure and sensitization mechanism of wheat allergens. Among various analytical tools, mass spectrometry (MS) is known to have high specificity and sensitivity. It is a promising non immune method to evaluate and quantify wheat allergens. In this article, the current research on the detection of wheat allergens based on mass spectrometry is reviewed. This review provides guidance for the further research on wheat allergen detection using mass spectrometry, and speeds up the development of wheat allergen research in China. [ABSTRACT FROM AUTHOR]

Cereals are the main source of energy, protein, B vitamins and minerals for the world population. Due to its ease of harvest and its resistance, wheat is the most cultivated and consumed cereal worldwide. Allergic reactions to wheat are rare, their prevalence in pediatric patients varies from 0.5-1.0%, being more frequent in areas such as Japan and northern Europe and in adults, although less frequent, they have also been described. The prognosis of allergy to wheat in childhood is favourable, but there are more severe cases that remain allergic until adolescence or adulthood; in these cases, oral tolerance induction (OTI) can be considered as a therapeutic alternative to the avoidance diet. We presented a case of 32-year-old patient with the onset of wheat allergy in adulthood with severe anaphylaxis. To date, there is no report of OTI with wheat in allergic adult patient, similar to the one described in this report. [ABSTRACT FROM AUTHOR]

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed.

Amylase trypsin inhibitors (ATIs) play an important role in wheat allergies and potentially in non-coeliac wheat sensitivity. Food processing could be important to mitigate the pathogenic properties of ATIs, e.g., by denaturation, glycation, enzymatic hydrolysis, cross-linking, and oxidation and reduction. These modifications also impact the solubility and extractability. The complex solubility behaviour of ATI isoforms (water and salt soluble, but also chloroform–methanol soluble, solubility depending on the redox state) becomes even more complex upon processing due to denaturation and (bio)chemical modifications. This significantly hinders the feasibility of quantitative extraction. Moreover, changes in biofunctionality may occur during the process of extraction, and the changes in ATI due to food processing will be more difficult to assess. Heat treatment decreases the extractability of ATIs with water, NaCl, and other buffer extracts, and binding of IgE from wheat-allergic persons to ATIs as observed with Western blotting is decreased or absent. IgE binding is reduced with the total extract in chaotropic and reducing agents. However, it can be increased when the proteins are hydrolyzed by proteases. Fermentation involving certain species of Fructolactobacilli (FLB), followed by baking, decreases the amount of ATIs and IgE binding to ATIs. In yeast-fermented bread, the amount of ATIs decreased in a similar manner, but IgE binding was more prominent, indicating that there was a modification of ATIs that affected the epitope recognition. When isolated ATIs are ingested with high ATI degrading FLB, the immune response in mice is less elevated in vivo, when compared with ATI without high ATI degrading FLB. The pathogenic effects on the skin of dogs and one wheat-allergic child are also decreased when soluble proteins or isolated ATIs are reduced with the thioredoxin/thioredoxin reductase NADPH system. Glycation on the other hand has been shown to potentiate the allergenic properties of ATIs as evidenced by the large increase in IgE binding. The impact of food processing on the pathogenic properties of ATIs is hardly studied in vivo in humans. There seem to be opportunities to mitigate the pathogenic properties in vitro, but potentiation of pathogenic properties is also frequently observed. This requires a deeper understanding on the impact of food processing on the pathogenicity of ATIs.

Gluten is the most common protein in wheat and is related to different pathogeneses. There are three main gluten-related disorders: celiac disease (CD), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS). Clinical manifestations are strictly related in all of them, such as abdominal pain and distention, however the development pathways may differ. The diagnosis criteria are also different, in CD features immunological markers such as IgA, while WA presents IgE markers, and NCGS does not have any specific immunological marker. The consumption of wheat, and consequently gluten-related products, is historical and it has grown over human evolution, which leads us to question what role this component plays in other diseases, and the consequence of a gluten-free diet (GFD). GFD is the treatment with major efficacy in CD and, likewise, is related with improvements in neuropathologies (autism spectrum disorder, anxiety, depression and schizophrenia), obesity, and the gut microbiome. Further investigation is required. GFD studies in people who do not present CD seem to be safe, especially when products containing gluten are not replaced by processed gluten-free products but by minimally processed foods, and also when the food strategy is accompanied by a qualified professional. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effect of the addition of tannins from unutilized resources on wheat allergen reduction, antioxidant properties, and quality by substituting 3%, 5%, and 10% of the flour with chestnut inner skin (CIS) and young persimmon fruit (YPF) powders to produce cookies. The enzyme-linked immunosorbent assay and Western blotting showed significantly lower wheat allergen content in CIS- or YPF-substituted cookies than in control cookies, and this effect was pronounced for CIS-substituted cookies. In addition, the tannin content and antioxidant properties of the CIS- or YPF-substituted cookies were markedly higher than those of the control cookies. Quality analysis of the CIS- and YPF-substituted cookies showed that the specific volume and spread factor, which are quality indicators for cookies, were slightly lower in the CIS- and YPF-substituted cookies than in the control cookies. Compared to the control, CIS substitution did not affect the breaking stress and total energy values of the cookies; however, YPF substitution at 10% increased these values. Color was also affected by the addition of CIS and YPF. The results suggest that the addition of CIS and YPF can reduce wheat allergens in cookies and improve tannin content and antioxidant properties. [ABSTRACT FROM AUTHOR]

Introduction: We describe celiac disease epidemiology in the US military population. Methods: This is a population-based study from data collected between 2000 and 2021. Incidence and prevalence rates and descriptive statistics for demographics are presented. Results: Overall, 2248 incident cases of celiac disease were identified. The incidence rate increased from 1.2 to 14.0 per 100,000 person-years and the overall lifetime prevalence increased from 3.1 to 57.4 per 100,000 service members. In gastroenterology clinics, the incidence rate increased from 1.4 to 8.2 per 100,000 person-years, while prevalence increased from 3.3 to 33.4 per 100,000 service members. Discussion: In this study, celiac disease incidence and prevalence increased significantly. [ABSTRACT FROM AUTHOR]

Celia M Zubrinich,1,2 Robert M Puy,3 Robyn E O’Hehir,1,3 Mark Hew1,2 1Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; 2School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 3Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Celia M Zubrinich, Email c.zubrinich@alfred.org.auBackground: Different phenotypes of food allergy may exist, exhibiting distinct clinical features, and driven by different pathogenic mechanisms. We compared omega-5-gliadin (O5G) allergy to peanut allergy, focusing on clinical features, reaction rates and triggers, and quality of life (QOL).Methods: We surveyed adults with O5G allergy and peanut allergy regarding their diagnosis, co-morbidities, allergic reactions, and QOL measured by the FAQLQ-AF.Results: We received responses from 43/80 (54%) individuals with O5G allergy and 43/130 (33%) with peanut allergy. Compared to peanut allergic individuals, those with O5G allergy were older at age of onset (37.2 vs 2.5 years, p < 0.001), had fewer additional atopic conditions (0.88 vs 2.93, p < 0.001) or food allergies (0.15 vs 1.86, p < 0.001), and more frequent reactions before diagnosis (1.085 vs 0.29 per month, p < 0.05) Reaction rates improved in both groups following diagnosis. Reactions to peanut were more often triggered by accidental exposure (84% vs 26%, p < 0.001) and being away from home (65% vs 28%, p < 0.001), while reactions to O5G were more often due to deliberate ingestion (30% vs 9%, p < 0.05) or unexpected exercise (35% vs 2%, p < 0.001). Overall QOL score was similar between groups (4.2 in O5G allergy, 4.7 in peanut allergy, p = 0.12), but worse among women and those with additional food allergies.Conclusion: Phenotypic differences between O5G and peanut allergy support the development of different clinical approaches and the possibility of targeting distinct pathogenic mechanisms for prevention and treatment. Quality of life was impaired to a similar degree between groups.Keywords: omega-5-gliadin allergy, wheat allergy, peanut allergy, food allergy, anaphylaxis, wheat-dependent exercise-induced allergy, WDEIA, food-dependent exercise-induced allergy, FDEIA, quality of life, QOL, Australia

Wheat allergy is a primary disease of food allergy, and its global prevalence is unclear. This study aimed to characterize the latest worldwide prevalence of wheat allergy based on five different diagnostic methods. Study searches were conducted in Web of Science, PubMed, Ovid LWW, and Cochrane database, with a time limit of 1 January 2007 to 1 September 2022. The review and screening of the articles was undertaken by two independent reviewers. The statistical analysis was conducted by R. A total of 56 articles were finally included. The prevalence of wheat allergy was 0.63% (95% CI: 0.43–0.87%) for self-reported, 0.70% (95% CI: 0.18–1.22%) for self-reported physician-diagnosed, 0.22% (95%CI: 0.07–0.65%) for skin prick test positive, 0.97% (95% CI: 0.43–2.20%) for specific immunoglobulin E positive, and 0.04% (95% CI: 0–0.16%) for food challenge. However, food challenge can be largely subjective, and the results were only based two countries, so the prevalence of wheat allergy confirmed by food challenge may be not entirely trustworthy. In conclusion, investigating the prevalence of wheat allergy in the real world as accurately as possible will contribute to the prevention, management, and risk assessment of wheat allergy. [ABSTRACT FROM AUTHOR]

Wheat allergies are potentially life-threatening and, therefore, have become a major health concern at the global level. It is largely unknown at present whether genetic variation in allergenicity potential exists among hexaploid, tetraploid and diploid wheat species. Such information is critical in establishing a baseline allergenicity map to inform breeding efforts to identify hyper-, hypo- and non-allergenic varieties. We recently reported a novel mouse model of intrinsic allergenicity using the salt-soluble protein extract (SSPE) from durum, a tetraploid wheat (Triticum durum). Here, we validated the model for three other wheat species [hexaploid common wheat (Triticum aestivum), diploid einkorn wheat (Triticum monococcum), and the ancient diploid wheat progenitor, Aegilops tauschii], and then tested the hypothesis that the SSPEs from wheat species will exhibit differences in relative allergenicities. Balb/c mice were repeatedly exposed to SSPEs via the skin. Allergic sensitization potential was assessed by specific (s) IgE antibody responses. Oral anaphylaxis was quantified by the hypothermic shock response (HSR). The mucosal mast cell response (MMCR) was determined by measuring mast cell protease in the blood. While T. monococcum elicited the least, but significant, sensitization, others were comparable. Whereas Ae. taushcii elicited the least HSR, the other three elicited much higher HSRs. Similarly, while Ae. tauschii elicited the least MMCR, the other wheats elicited much higher MMCR as well. In conclusion, this pre-clinical comparative mapping strategy may be used to identify potentially hyper-, hypo- and non-allergenic wheat varieties via crossbreeding and genetic engineering methods. [ABSTRACT FROM AUTHOR]

The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals, including coeliac disease (CD), wheat allergy and non-celiac gluten sensitivity (NCGS). GRD are characterized by a large variety of clinical presentations with both intestinal and extra-intestinal manifestations. The latter may affect almost every organ of the body, including the skin. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous specific manifestation of CD, many other muco-cutaneous disorders have been associated to GRD. In this review, we analyzed the main features of dermatological diseases with a proven association with GRD and those that improve after a gluten-free diet, focusing on the newly described cutaneous manifestations associated with NCGS. Our main hypothesis is that a “cutaneous-gluten sensitivity,” as specific cutaneous manifestation of NCGS, may exist and could represent a diagnostic marker of NCGS.

Background: Wheat-induced anaphylaxis (WIA) is a serious and potentially life-threatening wheat allergy, more common in adults than in children. Little is known about the differences in clinical profiles in WIA among patients of various ages in China. Methods: We analyzed data retrospectively from an allergy department in a tertiary hospital that included 248 patients (208 adults and 40 children and adolescents) with a history of WIA. Results: We found that alcohol was more frequent in patients aged ≥50 years [older adults] (19.0%, 4/21) than in those aged 12–17 years [adolescents] (0%, 0/33; p = 0.019). The frequency of NSAID use in older adults (42.9%, 9/21) was significantly higher than that in adolescents (0%, 0/33; p

Background: The interval between antigen ingestion may influence the safety of oral food challenge tests (OFCs), especially in patients with severe food allergies. Methods: This retrospective chart review of OFCs eliciting objective reactions to wheat, egg, and milk that were performed between April 2012 and January 2021 evaluated an equivalent number of low-dose OFCs performed at 30-, 40-, or 60-min intervals. To avoid the influence of the potential allergy severity of the patients, the prediction scores of all intervals were matched. We evaluated the total symptom score (TS), total ingested dose, and the proportions of severe reactions (TS ≥ 30) and adrenaline use. Results: We analyzed 945 OFCs (wheat, n = 186; egg, n = 561; milk, n = 198). The 60-min OFC had significantly lower TS than the 30- and 40-min OFC methods in wheat (p

Gluten-related disorders are a heterogeneous group of clinical entities caused by intolerance to wheat, rye, and barley flour components. They occur in 3–5% of genetically predisposed persons and, based on pathogenic and clinical features, are classified into celiac disease, non-celiac gluten sensitivity, and wheat allergy. There are also specific entities such as dermatitis herpetiformis or gluten ataxia, which can occur either within the celiac disease or independently. This article based on the current knowledge shows the basic details of the pathogenesis, clinical expression, diagnosis, and treatment of these disorders.

Résumé: Le gluten est une protéine contenue dans le blé largement utilisée dans l'industrie alimentaire pour ses propriétés de texture et de goût. L'hypersensibilité au gluten non cœliaque (HGNC) est un syndrome défini par l'apparition de symptômes intestinaux et extra-intestinaux secondaires à l'ingestion de gluten et régressant après un régime sans. L'HGNC a une présentation clinique similaire à la maladie cœliaque mais s'en distingue par l'absence d'atteinte histologique de la muqueuse intestinale. La cause de l'HGNC est indéterminée mais une activité du système immunitaire inné et une augmentation de la perméabilité intestinale ont été observées. Le diagnostic est fait après exclusion d'une allergie au blé et d'une maladie cœliaque par la recherche d'anticorps spécifiques et des biopsies duodénales. Il peut être confirmé par un challenge au gluten, rarement effectué dans la pratique clinique. Contrairement à la maladie cœliaque, le risque de complications malignes et de malabsorption est absent et permet un régime avec une quantité de gluten adaptée aux symptômes. Malgré des traitements en cours d'étude, le régime sans gluten est le seul traitement recommandé de la maladie cœliaque et l'HGNC. La surveillance clinique, biologique et histologique préconisée pour la maladie cœliaque n'est pas nécessaire en cas d'HGNC. Gluten is a protein contained in wheat and widely used in the food industry for its texture and taste properties. It causes a spectrum of diseases that concerns 5% of the world's population. Non-celiac gluten sensitivity (NCGS) is a syndrome defined by the occurrence of intestinal and extra-intestinal symptoms in the days and weeks following intake of gluten that resolves after its discontinuation. NCGS has a clinical presentation similar to celiac disease but differs by the absence of histological involvement of the intestinal mucosa. The pathogenesis of NCGS is undetermined but innate immune system activity and increased intestinal permeability have been observed. The diagnosis is made after excluding wheat allergy and celiac disease by looking for specific antibodies and duodenal biopsies. It can be confirmed by a gluten challenge, which is rarely performed in clinical practice. Unlike celiac disease, the risk of malignant complications and malabsorption is absent in NCGS allowing a diet with a quantity of gluten adapted to symptoms. Despite treatments being studied, the gluten-free diet is the only recommended treatment for celiac disease and NCGS. The biological and histological monitoring recommended in celiac disease is not necessary in the case of NCGS. [ABSTRACT FROM AUTHOR]

Wheat is a worldwide staple food, yet some people suffer from strong immunological reactions after ingesting wheat-based products. Lactic acid bacteria (LAB) constitute a promising approach to reduce wheat allergenicity because of their proteolytic system. In this study, 172 LAB strains were screened for their proteolytic activity on gluten proteins and α-amylase inhibitors (ATIs) by SDS-PAGE and RP-HPLC. Gliadins, glutenins, and ATI antigenicity and allergenicity were assessed by Western blot/Dot blot and by degranulation assay using RBL-SX38 cells. The screening resulted in selecting 9 high gluten proteolytic strains belonging to two species: Enterococcus faecalis and Lactococcus lactis. Proteomic analysis showed that one of selected strains, Lc. lactis LLGKC18, caused degradation of the main gluten allergenic proteins. A significant decrease of the gliadins, glutenins, and ATI antigenicity was observed after fermentation of gluten by Lc. lactis LLGKC18, regardless the antibody used in the tests. Also, the allergenicity as measured by the RBL-SX38 cell degranulation test was significantly reduced. These results indicate that Lc. lactis LLGKC18 gluten fermentation can be deeply explored for its capability to hydrolyze the epitopes responsible for wheat allergy. [ABSTRACT FROM AUTHOR]

Amylase/trypsin inhibitors (ATIs) are widely consumed in cereal-based foods and have been implicated in adverse reactions to wheat exposure, such as respiratory and food allergy, and intestinal responses associated with coeliac disease and non-coeliac wheat sensitivity. ATIs occur in multiple isoforms which differ in the amounts present in different types of wheat (including ancient and modern ones). Measuring ATIs and their isoforms is an analytical challenge as is their isolation for use in studies addressing their potential effects on the human body. ATI isoforms differ in their spectrum of bioactive effects in the human gastrointestinal (GI), which may include enzyme inhibition, inflammation and immune responses and of which much is not known. Similarly, although modifications during food processing (exposure to heat, moisture, salt, acid, fermentation) may affect their structure and activity as shown in vitro, it is important to relate these changes to effects that may present in the GI tract. Finally, much of our knowledge of their potential biological effects is based on studies in vitro and in animal models. Validation by human studies using processed foods as commonly consumed is warranted. We conclude that more detailed understanding of these factors may allow the effects of ATIs on human health to be better understood and when possible, to be ameliorated, for example by innovative food processing. We therefore review in short our current knowledge of these proteins, focusing on features which relate to their biological activity and identifying gaps in our knowledge and research priorities. [ABSTRACT FROM AUTHOR]

Wheat consists mainly of gluten with about 30% gliadin and 50% glutenin, which give gluten its unique viscoelastic properties and also mainly associated with the cause of celiac disease. Although the hydrolysis of gluten has been characterized, the discovery of new gluten-based peptides with high affinity toward T-cells is challenging. Currently, the highly immunogenic 33-mer gliadin peptide is considered to be the main cause of celiac disease. Thus, having consistent data for different gluten peptides with their respective immunogenicity is urgently needed. This report summarizes the various immunogenic gluten peptides identified, and the ingestion of specific gliadin peptide leading to the onset of CD, caused by the immunogenic α/β-gliadins especially in relation to the binding sites on HLA-DQ2 and HLA-DQ8. [ABSTRACT FROM AUTHOR]

The early ingestion of food can prevent the onset of food allergy related to inducing oral tolerance (OT). We developed the Hokushin wheat line as a hypoallergenic wheat (1BS-18H) lacking ω5-gliadin, a major allergen of wheat-dependent exercise-induced anaphylaxis (WDEIA). The 1BS-18H wheat had lower ability of sensitization for ω5-gliadin compared with Hokushin wheat. Here, we evaluated the induction of OT to gluten and ω5-gliadin by the early consecutive ingestion of 1BS-18H gluten using a rat model of wheat allergy. Rats were subcutaneously immunized with commercial gluten or native ω5-gliadin following the daily oral administration of gluten. The daily oral administration of 1BS-18H gluten for 5 days before immunization suppressed the increase in gluten- or ω5-gliadin-specific IgE and IgG1 antibodies induced by immunization to a level similar to Hokushin gluten. Intravenous challenge with gluten or ω5-gliadin did not decrease the rectal temperature in rats with OT induced by 1BS-18H or Hokushin gluten, although it was decreased in non-OT rats. In conclusion, the early consecutive ingestion of 1BS-18H wheat before sensitization induced OT to gluten and ω5-gliadin. These findings support the benefit of 1BS-18H wheat to prevent wheat allergy including WDEIA by consecutive ingestion in humans. [ABSTRACT FROM AUTHOR]

Introduction: Although separate immunogenic mechanisms are involved, IgE-type sensitization to wheat and celiac disease (CD) may coexist. We observationally assessed the importance of this relationship in daily practice using CD and wheat sensitization screenings., Methods: Celiac antibody (CA) screening and food prick tests (FPTs) were requested simultaneously from patients who presented to the Allergy Clinic between January 2022 and December 2023 and had any complaint accompanied by CD symptoms/findings (non-celiac group). Patients with positive CA (CA+) underwent endoscopy. As another group, FPT results were recorded for patients previously diagnosed with CD following a gluten-free diet (celiac group)., Results: In total, 169 patients (124 non-celiac and 45 celiac) were included in the study. Wheat prick positivity (WP+) was observed in 1 patient with CD. Among 65 WP+ patients without a CD diagnosis, 14 (20.3%) tested positive for CA+, and histopathology detected CD in 4 of these cases. Among the 59 WP- patients, 4 (8.8%) had CA+. The CA+ status of those with WP+ was significantly higher than those with WP- (p = 0.023)., Conclusion: The 4 patients unaware of their CD exhibited WP+, with a higher rate of CA+ observed in the WP+ group. The association between WP+ and CA+ suggests that an impaired intestinal barrier may lead to simultaneous T helper 1 and 2 type inflammatory responses. Although different types of sensitization to the same food would not typically be expected, growing evidence indicates that this phenomenon does occur. Further studies are necessary to confirm these findings and to explore the underlying causes., (© 2024 S. Karger AG, Basel.)

Background: The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut., Objective: We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay., Methods: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from α-/β-gliadin, γ-gliadin, ω-5-gliadin, and high- and low-molecular-weight glutenin were commercially synthesized and coupled to LumAvidin beads (Luminex Corporation, Austin, Tex). Machine learning methods were used to identify diagnostic epitopes, and performance was evaluated using the DeLong test., Results: The analysis included 122 children (83 wheat-allergic and 39 wheat-tolerant; 57.4% male). Machine learning coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1, to be the most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis showed lower es-IgG1 binding intensity than did all the other groups. A set of 4 informative epitopes from ω-5-gliadin and γ-gliadin were the best predictors of wheat allergy, with an area under the curve of 0.908 (sensitivity, 83.4%; specificity, 88.4%), higher than the performance exhibited by wheat-specific IgE (area under the curve = 0.646; P < .001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 nonallergic), with an area under the curve of 0.908 (sensitivity, 75.9%; specificity, 90.5%)., Conclusions: The wheat bead-based epitope assay demonstrated greater diagnostic accuracy compared with existing specific IgE tests for wheat allergy., Competing Interests: Disclosure statement This research project was supported by a grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University (grant no. Internal Order [IO] R016232026) and by the David H. and Julia Koch Research Program in Food Allergy Research. Disclosure of potential conflict of interest: M. Suárez-Fariñas reports consultancy feeds from DBV Technologies. M. Suprun is currently an employee at Janssen Pharmaceutical. H. A. Sampson reports funding to his institution for grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases; has received consulting fees from DBV Technologies, N-Fold Therapeutics, LLC, and Siolta, Inc; and has received stock options from DBV Technologies and N-Fold Therapeutics, LLC. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Gluten comprises an intricate network of hundreds of related but distinct proteins, mainly "gliadins" and "glutenins," which play a vital role in determining the rheological properties of wheat dough. However, ingesting gluten can trigger severe conditions in susceptible individuals, including celiac disease, wheat allergy, or non-celiac gluten sensitivity, collectively known as gluten-related disorders. This review provides a panoramic view, delving into the various aspects of gluten-triggered disorders, including symptoms, diagnosis, mechanism, and management. Though a gluten-free diet remains the primary option to manage gluten-related disorders, the emerging microbial and plant biotechnology tools are playing a transformative role in reducing the immunotoxicity of gluten. The enzymatic hydrolysis of gluten and the development of gluten-reduced/free wheat lines using RNAi and CRISPR/Cas technology are laying the foundation for creating safer wheat products. In addition to biotechnological interventions, the emerging artificial intelligence technologies are also bringing about a paradigm shift in the diagnosis and management of gluten-related disorders. Here, we provide a comprehensive overview of the latest developments and the potential these technologies hold for tackling gluten sensitivity.

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.

Introduction: Gluten is a mixture of wheat, rye and barley storage proteins. These corps have provided human beings worldwide with energy and nutrients for centuries. However, an increase in the occurrence of symptoms after the consumption of gluten has been observed recently. Although celiac disease is an indication of strict adherence to the gluten-free diet (GFD), the popularity of GFD is growing among healthy people. The risks of unsupported gluten elimination should be assessed before the introduction of GFD. Purpose: The study aims to define GFD and indicate who should follow the diet, as well as present difficulties concerning strict adherence to GFD and possible consequences of eliminating gluten on one’s own. Description of the state of knowledge: Regarding the mechanism, in which the symptoms after gluten consumption develop, the following diseases have been distinguished: celiac disease (CD), wheat allergy and non-celiac gluten sensitivity. Currently, the only indication of strict long-life adherence to GFD is CD. Such a restrictive approach may cause financial and social problems. Although the introduction of GFD improves the quality of life in CD patients, it does not lead to the immediate disappearance of the symptoms. Healthy people, who decide to eliminate gluten, should balance their diet carefully, as GFD might cause nutritional deficiencies and metabolic diseases. Summary: Strict long-life adherence to GFD is indicated in CD. This treatment may be problematic, which often is not evident to people who eliminate gluten on their own. Unbalanced GFD can lead to nutritional deficiencies as well as metabolic diseases.

The present study aimed to investigate the effect of the addition of tannins from unutilized resources on wheat allergen reduction, antioxidant properties, and quality by substituting 3%, 5%, and 10% of the flour with chestnut inner skin (CIS) and young persimmon fruit (YPF) powders to produce cookies. The enzyme-linked immunosorbent assay and Western blotting showed significantly lower wheat allergen content in CIS- or YPF-substituted cookies than in control cookies, and this effect was pronounced for CIS-substituted cookies. In addition, the tannin content and antioxidant properties of the CIS- or YPF-substituted cookies were markedly higher than those of the control cookies. Quality analysis of the CIS- and YPF-substituted cookies showed that the specific volume and spread factor, which are quality indicators for cookies, were slightly lower in the CIS- and YPF-substituted cookies than in the control cookies. Compared to the control, CIS substitution did not affect the breaking stress and total energy values of the cookies; however, YPF substitution at 10% increased these values. Color was also affected by the addition of CIS and YPF. The results suggest that the addition of CIS and YPF can reduce wheat allergens in cookies and improve tannin content and antioxidant properties.

Wheat allergies are potentially life-threatening because of the high risk of anaphylaxis. Wheats belong to four genotypes represented in thousands of lines and varieties. Monitoring changes to wheat allergens is critical to prevent inadvertent ntroduction of hyper-allergenic varieties via breeding. However, validated methods for this purpose are unavailable at present. As a proof-of-concept study, we tested the hypothesis that salt-soluble wheat allergens in our mouse model will be identical to those reported for humans. Groups of Balb/cJ mice were rendered allergic to durum wheat salt-soluble protein extract (SSPE). Using blood from allergic mice, a mini hyper-IgE plasma bank was created and used in optimizing an IgE Western blotting (IEWB) to identify IgE binding allergens. The LC-MS/MS was used to sequence the allergenic bands. An ancient Aegilops tauschii wheat was grown in our greenhouse and extracted SSPE. Using the optimized IEWB method followed by sequencing, the cross-reacting allergens in A. tauschii wheat were identified. Database analysis showed all but 2 of the durum wheat allergens and all A. tauschii wheat allergens identified in this model had been reported as human allergens. Thus, this model may be used to identify and monitor potential changes to salt-soluble wheat allergens caused by breeding. [ABSTRACT FROM AUTHOR]

Introduction: Wheat is the most important cereal for human nutrition but its high consumption is associated to an increasing complaint of wheat-related disorders, many of which are allergic in nature and different in respect to the involved allergens. In this study, we compared the clinical aspects of wheat allergy presented by patients sensitized to Tri a 19 in respect to those presented by patients sensitized to Tri a 14. Methods: With this aim, we selected patients sensitized to 1 or both of the 2 allergens, and among these we identified those who were really wheat allergic and reactive on the basis of a standardized methodology. We evaluated the clinical features such as the kind and severity of symptoms, the coexistence of triggering factors such as physical exercise and NSAIDs and alcohol consumption, and the association with other allergens and with various immunologic parameters. Wheat allergy in Tri a 19 sensitized patients was confirmed through a questionnaire while the patients sensitized to Tri a 14 underwent wheat challenge with 100 g of pasta followed by exercise on a treadmill. Results: Seventy-nine patients sensitized to Tri a 14 and 40 patients sensitized to Tri a 19 were recruited. The 2 sensitizations were independent with a significant inverse relation (p < 0.00001). The Tri a 19 sensitized patients presented, in respect to the Tri a 14 sensitized ones, an older age (p = 0.0017), a higher risk to be wheat allergic (p < 0.0001), a higher severity of the reactions (p < 0.00001) and a higher association with some cofactors, namely alcohol (p < 0.0005) and physical exercise (p = 0.003). On the contrary, Tri a 14 sensitization was associated with atopy (p < 0.0001), with a higher probability of patients being asymptomatic (p < 0.0001) and being sensitized to other foods, in particular to nuts and cereals (p < 0.00001). Conclusions: Sensitization to Tri a 19 or Tri a 14 determines different clinical pictures. In particular, sensitization to Tri a 19 implies a higher probability of severe reactions, even dependent on daily triggers, while that to Tri a 14 implies a higher cross-reactivity with other foods but it's more frequently asymptomatic, making a food challenge necessary to prevent useless food avoidance. [ABSTRACT FROM AUTHOR]

Objective: Celiac disease (CD) is an autoimmune-mediated disease characterized by small intestinal mucosal damage after gluten exposure in genetically predisposed individuals. Although it is known that the prevalence of CD in siblings of celiac patients is more common than the normal population, there are limited studies on the frequency of non-celiac gluten sensitivity (NCGS) and wheat allergy (WA). In this study, we aimed to investigate the prevalence of CD, NCGS and WA in siblings of children with CD. Material and Methods: Siblings of patients diagnosed with CD in our pediatric gastroenterology clinic were examined for CD, NCGS and WA. CD diagnosed according to The European Society for Paediatric Gastroenterology Hepatology and Nutrition guideline. NCGS was diagnosed with the disappearance of symptoms related to gluten intake with gluten elimination, while WA was diagnosed with the absence of wheat-related symptoms after wheat removal from the diet and wheat-specific immunoglobulin E assays. Demographic and clinical features and laboratory parameters of the cases were recorded. Results: 50 siblings of 59 celiac patients eligible for the study [25 males (50%), mean age±standard deviation; 11.5±3.66 years (4-17 years)] were included. Three of the siblings [6%, 95% confidence interval (CI): 1.56-17.54) were diagnosed with CD, and 7 (14%, 95% CI: 6.28-27.36) were diagnosed with NCGS. There was no sibling with a diagnosis of WA. Conclusion: In our study, both CD and NCGS were found to have a higher prevalence in siblings of CD patients. When screening siblings of patients with CD, cases with symptoms and normal serology and endoscopy findings should be evaluated for NCGS. [ABSTRACT FROM AUTHOR]

Various gluten-related diseases (celiac disease, wheat allergy, gluten sensitivity) are known and their incidence is growing. Gluten is a specific type of plant storage protein that can impair the health of gluten-prone persons following consumption, depending on the origin. The most severe effects are induced by wheat, barley, and rye. The only treatment is based on the absolute avoidance of those foods, as even traces might have severe effects on human well-being. With the goal of binding gluten impurities after ingestion, an in vitro setting was created. A special processed kind of zeolite, purified clinoptilolite-tuff (PCT), was implemented as an adsorber of gluten derived from different origins. Zeolites are known for their excellent sorption capacities and their applications in humans and animals have been studied for a long time. Tests were also performed in artificial gastric and intestinal fluids, and the adsorption capacity was determined via a certified validated method (ELISA). Depending on the kind of gluten source, 80–130 µg/mg of gluten were bound onto PCT. Hence, purified clinoptilolite-tuff, which was successfully tested for wheat, barley, and rye, proved to be suitable for the adsorption of gluten originating from different kinds of crops. This result might form the basis for an expedient human study in the future. [ABSTRACT FROM AUTHOR]

Surapon Piboonpocanun,1 Torpong Thongngarm,2 Chamard Wongsa,2 Punchama Pacharn,3 Onrapak Reamtong,4 Mongkhon Sompornrattanaphan2 1Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand; 2Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Division of Allergy and Clinical Immunology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 4Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandCorrespondence: Mongkhon SompornrattanaphanDivision of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandTel +66 24198263Email mongkhon.som@mahidol.ac.thBackground: Various clinical patterns based on routes of sensitization and sensitized allergens are reported in adult-onset IgE-mediated wheat allergy. There is still a paucity of data on IgE-bound wheat allergen profiles in wheat challenge-proven adult-onset wheat allergic cases. Therefore, we aim to identify the major sensitized allergens in Thai adult-onset wheat allergic patients whose first symptom occurred after the age of 18 years despite previous tolerance.Methods: This cross-sectional pilot study recruited patients from the Thai Adult-onset IgE-mediated Wheat Allergy Cohort (TAWAC). The sera of patients with mostly challenge-proven cases were selected for allergen study, including ImmunoCAP and IgE-bound gliadins along with glutenins profiles. The IgE-bound proteins were identified by liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). Direct binding of IgE to recombinant gliadin and glutenin was performed to confirm the results of immunoblot and LC-MS/MS.Results: Eleven wheat-dependent exercise-induced anaphylaxis (WDEIA) and 4 typical wheat allergy (WA) patients were enrolled. Serum IgE from > 50% of bound proteins had a molecular weight ranging from 35 to 55 kDa in both gliadin and glutenin extracts. Further, ELISA demonstrated that γ-gliadin and ω 5-gliadin were the most important major allergens. Other major allergens include α/β-gliadin, HMW glutenin, and possibly α-amylase inhibitor or LWM glutenin. Gamma-gliadin sensitization was found in all WA patients (4/4), while ω-5 gliadin was found in all WDEIA patients (11/11) from ELISA.Conclusion: Wheat γ-gliadin and ω-5 gliadin are major wheat allergens among adult-onset wheat allergy patients in Thailand. Component-resolved diagnosis using γ-gliadin might be helpful in high suspicion of wheat allergy.Keywords: allergens, anaphylaxis, enzyme-linked immunosorbent assay, food allergy, gliadins, gluten, immediate hypersensitivity, prolamin, wheat allergy

Wheat is a major food allergen per the regulatory bodies of various nations. Hypersensitivity reactions to wheat have been steadily increasing for reasons that are not completely understood. Wheat-allergy models typically use adjuvants to induce sensitization to wheat proteins followed by an intraperitoneal challenge to elicit anaphylaxis. Although these models are very useful, they lack the ability to reveal the intrinsic allergenicity potential of wheat. To improve the mouse model of wheat allergy, we tested the hypothesis that repeated skin application of salt-soluble protein extract (SSPE) from durum wheat will clinically sensitize the mice to oral anaphylaxis to SSPE. Balb/c mice were bred and maintained on a plant-protein-free diet and used in the experiments. Adult female mice were exposed to SSPE once a week for 9 weeks via a solution on intact skin. Sensitization was measured by SSPE-specific IgE (sIgE) antibody and total IgE (tIgE) levels. Oral anaphylaxis was quantified by hypothermic shock response (HSR), and mucosal mast cell response (MMCR) was quantified by measuring MMCP-1 after oral challenge. Using single mouse data, correlation analyses were performed to determine the relationship among the allergenicity readouts. Spleen cytokines were quantified using a protein microarray method. Our results show that (i) repeated skin exposures to SSPE elicited robust increases in the sIgE and tIgE levels; (ii) skin exposure to SSPE was sufficient to sensitize mice for oral anaphylaxis and MMCR; (iii) both HSR and MMCR showed a strong correlation with each other, as well as with sIgE, and a modest correlation with tIgE levels; (iv) selected Th2/Th17/Th1 cytokines were elevated in skin-sensitized mice; and (v) oral allergen-challenged mice showed selective elevation of IL-6 and a panel of chemokines compared to saline-challenged mice. Together, we report the development and characterization of a novel adjuvant-free wheat-allergy mouse model that uses skin sensitization without tape-stripping followed by oral elicitation of anaphylaxis. Furthermore, validation of quantifiable wheat allergenicity readouts makes this model particularly suitable as a pre-clinical testing tool to assess the intrinsic sensitization/oral-anaphylaxis elicitation potential of novel wheat proteins (e.g., processed wheat) and to develop hypo/non-allergenic wheat products.

Celia Zubrinich,1,2 Robert Puy,1,3 Robyn O’Hehir,1,3 Mark Hew1,2 1Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; 2School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 3Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Celia Zubrinich Email c.zubrinich@alfred.org.auBackground: Allergy to the omega-5-gliadin component of gluten (O-5-G allergy) often manifests when wheat ingestion is followed by a co-factor, usually exercise. There is no established best approach to management.Objective: We sought to identify the beneficial effects, firstly of establishing a firm diagnosis, and secondly of stringent management, either by avoiding gluten ingestion altogether or separating it temporally from exercise by at least 4 hours. We also determined how frequently patients adhered to their physicians’ clinical recommendations.Methods: We undertook a survey of individuals diagnosed with O-5-G allergy at our institution over 8 years, who had a consistent clinical history and confirmatory laboratory evidence.Results: Of 80 eligible individuals, 43 responded (54%). Symptoms began in adulthood for all bar one, and concurrent asthma and eczema was uncommon (9% prevalence, respectively). Median time to diagnosis was 2 years. Achieving a diagnosis reduced the rate of reactions (0.35 per month vs 1.085 reactions per month, p=0.029). Many patients (10/43) did not adhere to the recommended stringent approach, to either avoid wheat/gluten or separate food and exercise by 4 hours. However, those adopting a stringent approach had a substantially lower risk of recurrent allergic reaction (0.22 per month vs 0.74 per month, p=0.004).Conclusion: The epidemiology of O-5-G allergy implies pathogenic mechanisms potentially distinct from those of childhood-onset food allergy. Accurate diagnosis improves the clinical trajectory, primarily through the adoption of a stringent management approach.Keywords: omega-5-gliadin allergy, wheat allergy, food allergy, anaphylaxis, wheat-dependent exercise-induced anaphylaxis, WDEIA, food-dependent exercise-induced anaphylaxis, FDEIA