Routinely Used and Emerging Diagnostic and Immunotherapeutic Approaches for Wheat Allergy.

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.

Wheat-Related Disorders in Children: A 360-Degree View.

Immunological illnesses related to wheat represent an epidemiologically relevant phenomenon at a pediatric age. The term "Wheat-related disorders" involves a spectrum of diseases: celiac disease, IgE-mediated wheat allergy, non-IgE mediated wheat allergy, wheat-related eosinophilic esophagitis, and non-celiac gluten sensitivity. Their pathogenesis is different. At the same time, wheat represents their common point. This article aims to the state-of-the-art and new clinical evidence in pediatric age.

The top 100 most cited articles in the past 30 years of wheat allergy: a bibliometric analysis.

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," "wheat-dependent 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 most-cited 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.

Test Panel of Hidden Allergens for "Idiopathic Anaphylaxis" Reveals Wheat Allergy Dependent on Augmentation Factors as Common Final Diagnosis.

BACKGROUND: Idiopathic anaphylaxis (IA) is an unresolved concern. Hidden allergens may be relevant in IA and in nonsteroidal anti-inflammatory drug hypersensitivity (NSAID-HS). OBJECTIVE: To identify hidden elicitors for IA and NSAID-HS by a skin prick test (SPT) (13 allergens) and allergen-specific IgE (sIgE) panel (12 allergens) and to determine the value of each tested allergen. METHODS: We retrospectively included all patients from 2018 to 2021 referred with a suspicion of IA or NSAID-HS by history in whom SPT and/or sIgE to allergens of the IA panel were performed. Patient characteristics from patients' records included comorbidities, history and symptoms of anaphylaxis, serum baseline tryptase level, total IgE level, SPT, sIgE, challenge results, and final diagnoses. RESULTS: A total of 134 patients (77 female, mean age 39.7 ± 14.6 years) were included. Median serum baseline tryptase and total IgE levels were 4.23 µg/L and 133.5 kU/L, respectively. Allergologic workup with the IA panel resulted in positive SPT and sIgE in 61 (47%) and 66 (60%) patients, respectively. In those, confirmation or exclusion of allergy, mostly by challenge, led to a definitive diagnosis in 61 of 134 patients (46%). Skin prick test was most frequently positive to gluten (22.4%) and sIgE to ω5-gliadin (21.6%), which correlated with the history (r = 0.310, P < .001; and r = 0.407, P < .001, respectively). In 28 of 134 patients (21%) with initially suspected IA or NSAID-HS, challenges confirmed occult food allergy in which wheat allergy dependent on augmentation factors was the most frequent cause of anaphylaxis (19%). CONCLUSIONS: Wheat allergy dependent on augmentation factors should be considered in all patients with anaphylaxis of unknown cause or after NSAID intake.

Detection of Sensitization Profiles with Cellular In Vitro Tests in Wheat Allergy Dependent on Augmentation Factors (WALDA).

Wheat allergy dependent on augmentation factors (WALDA) is the most common gluten allergy in adults. IgE-mediated sensitizations are directed towards ω5-gliadin but also to other wheat allergens. The value of the different in vitro cellular tests, namely the basophil activation test (BAT) and the active (aBHRA) and passive basophil histamine-release assays (pBHRA), in the detection of sensitization profiles beyond ω5-gliadin has not been compared. Therefore, 13 patients with challenge-confirmed, ω5-gliadin-positive WALDA and 11 healthy controls were enrolled. Specific IgE (sIgE), skin prick tests, BATs, aBHRA, and pBHRA were performed with allergen test solutions derived from wheat and other cereals, and results were analyzed and compared. This study reveals a distinct and highly individual reactivity of ω5-gliadin-positive WALDA patients to a range of wheat allergens beyond ω5-gliadin in cellular in vitro tests and SPT. In the BAT, for all tested allergens (gluten, high-molecular-weight glutenin subunits, α-amylase/trypsin inhibitors (ATIs), alcohol-free wheat beer, hydrolyzed wheat proteins (HWPs), rye gluten and secalins), basophil activation in patients was significantly higher than in controls (p = 0.004-p < 0.001). Similarly, significant histamine release was detected in the aBHRA for all test substances, exceeding the cut-off of 10 ng/mL in all tested allergens in 50% of patients. The dependency of tests on sIgE levels against ω5-gliadin differed; in the pBHRA, histamine release to any test substances could only be detected in patients with sIgE against ω5-gliadin ≥ 7.7 kU/L, whereas aBHRA also showed high reactivity in less sensitized patients. In most patients, reactivity to HWPs, ATIs, and rye allergens was observed. Additionally, alcohol-free wheat beer was first described as a promising test substance in ω5-gliadin-positive WALDA. Thus, BAT and aBHRA are valuable tools for the identification of sensitization profiles in WALDA.

Impact of food processing on the allergenic properties of amylase trypsin inhibitors from wheat.

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.

Low Allergenicity in Processed Wheat Flour Products Using Tannins from Agri-Food Wastes.

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.

Skin gluten-related disorders: new and old cutaneous manifestations to be considered.

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.

Clinical profiles of patients with wheat-induced anaphylaxis at various ages of onset.

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 < 0.001), and patients aged 18-49 years [young adults] (2.8%, 5/178; p < 0.001). During WIA, cardiovascular symptoms in children were less frequent than those in other age groups (children, 28.6%; adolescents, 87.9%; young adults, 93.0%; older adults, 95.2%; p < 0.001). The consciousness loss rate in adults (both age groups; p < 0.001) and the hypotension rate in older adults (p = 0.006) were higher than those in other age groups. Compared with adults (young and older adults), children had a higher rate of allergic comorbidities (p = 0.004, 0.001, respectively) and a higher rate of other food allergies (p < 0.001, <0.001, respectively). Compared with the mild-to-moderate anaphylaxis group, the severe anaphylaxis group had a higher onset age (p = 0.001), higher cofactor prevalence (p = 0.004), lower allergic comorbidity rate (p = 0.014), and higher positive rate of specific IgE to omega-5 gliadin (ω-5 gliadin) (p = 0.023). Conclusion: Clinical profiles of patients with WIA are different among various onset age/severity groups. An improved understanding of WIA symptoms in various age/severity groups could help accelerate diagnosis, suggest preventive measures, and contribute to improved patient care.

Development of a barley reference material for gluten analysis.

Celiac disease (CD) can be triggered in susceptible individuals by the consumption of gluten, a complex storage protein mixture present in wheat, rye and barley. There is no specific reference material (RM) available for barley and this leads to inaccurate quantitation of barley gluten in supposedly gluten-free foods. Therefore, the aim was to select representative barley cultivars to establish a new barley RM. The relative protein composition of the 35 barley cultivars averaged 25% albumins and globulins, 11% d-hordeins, 19% C-hordeins, and 45% B/γ-hordeins. The mean gluten and protein content was 7.2 g/100 g and 11.2 g/100 g, respectively. The prolamin/glutelin ratio (1:1) commonly used in ELISAs to calculate the gluten content was found to be inappropriate for barley (1.6 ± 0.6). Eight cultivars suitable as potential RMs were selected to ensure a typical barley protein composition and improve food safety for CD patients.

Celiac Disease on the Rise in the US Military Population: A 22 Year Retrospective Epidemiologic Study.

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.

Allergenicity of wheat protein in diet: Mechanisms, modifications and challenges.

Wheat is widely available in people's daily diets. However, some people are currently experiencing IgE-mediated allergic reactions to wheat-based foods, which seriously impact their quality of life. Thus, it is imperative to provide comprehensive knowledge and effective methods to reduce the risk of wheat allergy (WA) in food. In the present review, recent advances in WA symptoms, the major allergens, detection methods, opportunities and challenges in establishing animal models of WA are summarized and discussed. Furthermore, an updated overview of the different modification methods that are currently being applied to wheat-based foods is provided. This study concludes that future approaches to food allergen detection will focus on combining multiple tools to rapidly and accurately quantify individual allergens in complex food matrices. Besides, biological modification has many advantages over physical or chemical modification methods in the development of hypoallergenic wheat products, such as enzymatic hydrolysis and fermentation. It is worth noting that using biotechnology to edit wheat allergen genes to produce allergen-free food may be a promising method in the future which could improve the safety of wheat foods and the health of allergy sufferers.

A Meta-Analysis of the Prevalence of Wheat Allergy Worldwide.

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.

Intrinsic Allergenicity Potential of Salt-Soluble Protein Extracts from the Diploid, Tetraploid and Hexaploid Wheats: Validation Using an Adjuvant-Free Mouse Model.

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.

Characterization of rye flours and their potential as reference material for gluten analysis.

The safety of gluten-free products relies on accurate gluten analysis, most commonly using ELISA. These test kits are calibrated to gliadins or wheat gluten, because there is no reference material (RM) for rye. Our aim was to select representative samples out of 32 rye cultivars for use as RM. All cultivars were characterized by RP-HPLC, gel permeation HPLC and R5 and G12 ELISA. The protein and gluten content ranged from 5.5 to 11.2 g/100 g and 3.0 to 7.8 g/100 g, respectively. The average protein distribution was 40% albumins/globulins, 23% γ-75k-secalins, 17% γ-40k-secalins, 14% ω-secalins and 6% high-molecular-weight-secalins. The mean prolamin/glutelin ratio was 4.4 for rye and this translates to an estimated conversion factor from rye prolamins to gluten of 1.2, instead of the usual factor of 2. Seven cultivars were selected for RM production based on cluster analysis, geographical origin and availability to comprehensively cover the diversity of rye.

Phenotypic Distinctions Between Omega-5-Gliadin Allergy and Peanut Allergy: Clinical Profile, Reaction Rates and Triggers, and Quality of Life.

Background: 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.

An Adjuvant-Free Mouse Model Using Skin Sensitization Without Tape-Stripping Followed by Oral Elicitation of Anaphylaxis: A Novel Pre-Clinical Tool for Testing Intrinsic Wheat Allergenicity.

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.

Diagnostic management of patients reporting symptoms after wheat ingestion.

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.

Hypoallergenic Wheat Line (1BS-18H) Lacking ω5-Gliadin Induces Oral Tolerance to Wheat Gluten Proteins in a Rat Model of Wheat Allergy.

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.

Cross-reactivity of each fraction among cereals in children with wheat allergy.

BACKGROUND: Cross-reactivity between wheat and other cereals is a crucial issue in the management of wheat allergy. Few studies have reported in vitro cross-reactivity in immediate-type wheat allergy. The aim of this study aimed to examine cross-reactivity of the three fractions (albumin/globulin, gliadin, and glutenin fractions) among cereals in children with wheat allergy. METHODS: Sera from 128 children with immediate-type wheat allergy were collected. Specific immunoglobulin E (sIgE) levels against each fraction of wheat, barley, and rye were measured by enzyme-linked immunosorbent assay (ELISA). Cross-reactivities of each fraction among wheat, barley, and rye were examined via inhibition ELISA. RESULTS: All subjects were sensitized to all fractions of wheat, barley, and rye. The wheat sIgE levels were significantly higher than those of barley and rye in all the fractions (p ≤ .001) and were significantly correlated with sIgE levels in each fraction (r = .887-.969, p < .001). Inhibition ELISA revealed that wheat inhibited the IgE binding to most of the solid phases at lower protein levels compared with barley and rye in all fractions. CONCLUSIONS: In children with immediate-type wheat allergy, sensitization to all the three fractions of wheat was observed. In addition, they showed sensitization to barley and rye caused by in vitro cross-reactivity with wheat in each fraction. When managing children with wheat allergy, sensitization to barley and rye caused by the cross-reactivities should be considered.