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Keywords = wheat-dependent exercise-induced anaphylaxis

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15 pages, 1926 KB  
Article
Baseline Immune Signatures in Serum Extracellular Vesicles Distinguish Food-Induced from Wheat-Dependent Exercise-Induced Anaphylaxis
by Junda Li, Tengze Shang, Kai Guan and Jia Yin
Int. J. Mol. Sci. 2026, 27(11), 4732; https://doi.org/10.3390/ijms27114732 - 25 May 2026
Viewed by 257
Abstract
Food-induced anaphylaxis (FIA) is a life-threatening allergic reaction, while wheat-dependent exercise-induced anaphylaxis (WDEIA) is triggered by wheat ingestion plus cofactors. To elucidate their differences, we profiled serum extracellular vesicle (EV) proteomes from 240 participants, including WDEIA, FIA, oral allergy syndrome (OAS), and healthy [...] Read more.
Food-induced anaphylaxis (FIA) is a life-threatening allergic reaction, while wheat-dependent exercise-induced anaphylaxis (WDEIA) is triggered by wheat ingestion plus cofactors. To elucidate their differences, we profiled serum extracellular vesicle (EV) proteomes from 240 participants, including WDEIA, FIA, oral allergy syndrome (OAS), and healthy controls. All blood samples were obtained at least one month after the most recent acute allergic reaction, using TMT-based LC-MS/MS with ELISA validation. A total of 583 EV proteins were confidently identified, revealing distinct immune features. Compared with controls, EV-derived C1-inhibitor (C1-INH) significantly decreased in both WDEIA and FIA, showing diagnostic potential for systemic anaphylaxis. Seventy-six proteins differed between WDEIA and FIA, with reduced apolipoprotein E (APOE) in FIA and elevated eosinophil cationic protein (ECP) in WDEIA, both exhibiting good discriminatory power. These findings indicate that serum EV proteomics can reveal unique immune signatures and identify C1-INH, APOE, and ECP as potential biomarkers distinguishing food-related anaphylaxis subtypes. Full article
(This article belongs to the Special Issue Allergic Reactions and Immune Factors)
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26 pages, 2090 KB  
Review
Wheat Allergy in the Era of Precision Medicine: From Novel Molecular Markers to New Therapeutic Perspectives
by Solomiya Pukalyak, Weronika Gromek, Aleksandra Tomczak, Ewa Markut-Miotła, Maja Woźniak, Mariusz Wysokiński, Sylwia Smolinska and Emilia Majsiak
Int. J. Mol. Sci. 2026, 27(4), 1717; https://doi.org/10.3390/ijms27041717 - 10 Feb 2026
Cited by 2 | Viewed by 1271
Abstract
Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise [...] Read more.
Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise component-based diagnostics (CRDs) facilitates the management of wheat allergy. It has significantly improved the diagnostic accuracy for WDEIA ω-5-gliadin (Tri a 19), although considering new knowledge about wheat proteins, it seems necessary to include them in the diagnostic scheme, especially where Tri a 19 remains negative despite clinical symptoms. Therefore, in this review, we evaluate the clinical utility of new wheat molecules with a high risk of anaphylaxis. We pay particular attention to Tri a 37 (α-purothionin), a thermally stable allergen associated with a 4-fold increase in the risk of severe anaphylaxis, and Tri a 36 (LMW glutenin), which shows higher sensitivity than Tri a 19 in specific pediatric cohorts. In addition, we emphasize the role of Tri a 14 (nsLTP) in distinguishing true wheat sensitization from pollen-related cross-reactivity caused by profilins (Tri a 12) or carbohydrate determinants (CCDs). Beyond diagnostics, the review discusses dynamic changes in sensitization profiles in relation to the allergic march and the phenomenon of spontaneous remission in children. New management strategies are also discussed, including the potential of omalizumab (based on the data from the OUtMATCH study) in facilitating the reintroduction of allergens into the diet. Full article
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21 pages, 633 KB  
Review
Basophil Activation Test in IgE-Mediated Wheat Allergy: Diagnostic and Clinical Applications—A Narrative Review
by Elena Camelia Berghea, Mădălina Coman-Stanemir and Ioana Raluca Papacocea
Diagnostics 2025, 15(20), 2659; https://doi.org/10.3390/diagnostics15202659 - 21 Oct 2025
Cited by 2 | Viewed by 2530
Abstract
The basophil activation test (BAT) is an emerging tool in the diagnosis and management of IgE-mediated wheat allergies (WAs), particularly in complex or high-risk phenotypes. This narrative review explores the clinical applications of BAT across a spectrum of WA presentations, including wheat-dependent exercise-induced [...] Read more.
The basophil activation test (BAT) is an emerging tool in the diagnosis and management of IgE-mediated wheat allergies (WAs), particularly in complex or high-risk phenotypes. This narrative review explores the clinical applications of BAT across a spectrum of WA presentations, including wheat-dependent exercise-induced anaphylaxis (WDEIA), contact urticaria, and pediatric food allergy. The BAT provides a functional measure of allergen-triggered basophil activation, bridging the gap between mere sensitization and true clinical reactivity. We highlight its utility in detecting sensitization to specific wheat components such as ω-5 gliadin, glutenin subunits, and hydrolyzed wheat proteins, and its value in cases where traditional diagnostics are inconclusive. Furthermore, BAT is discussed as a dynamic biomarker in therapeutic monitoring, especially in patients receiving omalizumab, where reduced basophil reactivity correlates with improved clinical outcomes. While standardization and access remain challenges, the BAT holds significant promise as a precision diagnostic and monitoring tool in wheat allergies. Full article
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16 pages, 5619 KB  
Article
Allelic Analysis of the Gli-B1 Locus in Hexaploid Wheat Using Reverse-Phase–Ultra-Performance Liquid Chromatography
by Jong-Yeol Lee, Yu-Jeong Yang, Jinpyo So, Sewon Kim and Kyoungwon Cho
Molecules 2025, 30(3), 609; https://doi.org/10.3390/molecules30030609 - 30 Jan 2025
Cited by 1 | Viewed by 1735
Abstract
Wheat (Triticum aestivum L.) omega-5 gliadin, a major allergen responsible for wheat-dependent exercise-induced anaphylaxis in humans, is encoded by genes located at the Gli-B1 locus on chromosome 1B, which exhibits genetic polymorphism. Gli-B1 alleles have generally been identified based on the electrophoretic [...] Read more.
Wheat (Triticum aestivum L.) omega-5 gliadin, a major allergen responsible for wheat-dependent exercise-induced anaphylaxis in humans, is encoded by genes located at the Gli-B1 locus on chromosome 1B, which exhibits genetic polymorphism. Gli-B1 alleles have generally been identified based on the electrophoretic mobilities of the encoded gamma-, omega-1,2, and omega-5 gliadins in acid polyacrylamide gel electrophoresis. However, the similar mobilities of omega-5 gliadin variants make it difficult to distinguish them among different wheat varieties. In this study, we optimized reverse-phase–ultra-performance liquid chromatography (RP-UPLC) conditions to separate omega-5 gliadins in the reference wheat cultivar Chinese Spring and its nullisomic–tetrasomic lines for chromosome 1B. Five chromatographic peaks corresponded to omega-5 gliadin, and the average relative standard deviation to each peak retention time ranged from 0.31% to 0.93%, indicating that the method is accurate and reproducible for fractionating omega-5 gliadins in gliadin extracts from wheat flour. Using the optimized RP-UPLC method, we analyzed omega-5 gliadins in 24 wheat varieties with the Gli-B1f allele. The result showed that the wheat varieties were sorted into eight groups according to the composition of omega-5 gliadin, indicating that the classification of Gli-B1 alleles based on A-PAGE could not explain the composition of omega-5 gliadin in wheat. We reclassified 73 wheat varieties containing 16 unique Gli-B1 alleles into 31 groups based on the chromatographic patterns of their omega-5 gliadins. Our results provide information on the specific Gli-B1 alleles of wheat varieties belonging to each group and demonstrate the potential for RP-UPLC to facilitate genetic studies of wheat varieties. Full article
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16 pages, 479 KB  
Review
Allergenic Biomarkers in the Molecular Diagnosis of IgE-Mediated Wheat Allergy
by Mariana Preda, Florin-Dan Popescu, Emilia Vassilopoulou and Sylwia Smolinska
Int. J. Mol. Sci. 2024, 25(15), 8210; https://doi.org/10.3390/ijms25158210 - 27 Jul 2024
Cited by 16 | Viewed by 5583
Abstract
IgE-mediated wheat allergy can take on various forms, including childhood food allergy to wheat, wheat-dependent exercise-induced anaphylaxis in young adults, baker’s respiratory allergy/asthma in workers exposed to wheat flour inhalation, and contact urticaria that is caused by hydrolyzed wheat proteins in some cosmetics, [...] Read more.
IgE-mediated wheat allergy can take on various forms, including childhood food allergy to wheat, wheat-dependent exercise-induced anaphylaxis in young adults, baker’s respiratory allergy/asthma in workers exposed to wheat flour inhalation, and contact urticaria that is caused by hydrolyzed wheat proteins in some cosmetics, and that is sometimes associated with a food allergy. Singleplex and multiplex immunoassays detect specific IgE antibodies to wheat allergenic molecular biomarkers such as omega-5 gliadin Tri a 19, lipid transfer protein Tri a 14, and alpha-amylase inhibitors. The fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens is a commonly used singleplex assay. Multiplex methods include the ELISA-based macroarray immunoassay using nano-bead technology and a microarray immunoassay on polymer-coated slides. Another promising diagnostic tool is the basophil activation test performed with omega-5 gliadin and other wheat protein types. Detailed comprehension of the structural and immunological features of the numerous wheat allergens significant in clinical settings is imperative for advancing diagnostic biomarkers for IgE-mediated wheat allergies. Full article
(This article belongs to the Special Issue Recent Advances in Gluten-Related Disorders)
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11 pages, 2805 KB  
Article
Effect of Adding Chestnut Inner Skin on Allergenic Protein, Antioxidant Properties, and Quality of Bread
by Yoko Tsurunaga and Eishin Morita
Molecules 2024, 29(4), 863; https://doi.org/10.3390/molecules29040863 - 15 Feb 2024
Cited by 3 | Viewed by 2139
Abstract
Wheat-dependent, exercise-induced anaphylaxis has no fundamental cure and requires patients to refrain from wheat consumption or to rest after eating. Although hypoallergenic wheat production by enzymatic degradation or thioredoxin treatment has been investigated, challenges still exist in terms of labor and efficacy. We [...] Read more.
Wheat-dependent, exercise-induced anaphylaxis has no fundamental cure and requires patients to refrain from wheat consumption or to rest after eating. Although hypoallergenic wheat production by enzymatic degradation or thioredoxin treatment has been investigated, challenges still exist in terms of labor and efficacy. We investigated a hypoallergenic wheat product manufacturing technology that takes advantage of the property of tannins to bind tightly to proteins. Commercially available bread wheat (BW) and hypoallergenic wheat (1BS-18 “Minaminokaori”, 1BS-18M) were used. Chestnut inner skin (CIS) was selected as a tannin material based on the screening of breads with added unused parts of persimmon and chestnut. Hypoallergenicity was evaluated using Western blotting. The effect of CIS addition on the antioxidative properties of bread was also measured. For both BW and 1BS-18M, CIS addition reduced the immunoreactivity of wheat allergens. Antioxidant activities increased with increasing CIS substitution. However, 10% CIS-substituted breads were substantially less puffy. Five percent CIS substitution was optimal for achieving low allergenicity, while maintaining bread quality. The strategy investigated herein can reduce allergies related to wheat bread consumption. In this study, the evaluation of hypoallergenicity was limited to instrumental analysis. In the future, we will evaluate hypoallergenicity through clinical trials in humans. Full article
(This article belongs to the Special Issue Plant Foods Ingredients as Functional Foods and Nutraceuticals III)
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14 pages, 3322 KB  
Perspective
A Narrative Mini Review on Current Status of Hypoallergenic Wheat Development for IgE-Mediated Wheat Allergy, Wheat-Dependent Exercise-Induced Anaphylaxis
by Eishin Morita, Hiroaki Matsuo, Kunie Kohno, Tomoharu Yokooji, Hiroyuki Yano and Takashi Endo
Foods 2023, 12(5), 954; https://doi.org/10.3390/foods12050954 - 23 Feb 2023
Cited by 18 | Viewed by 4713
Abstract
Immunoglobulin E (IgE)-mediated food allergies to wheat that develop after school age typically shows a type of wheat-dependent exercise-induced anaphylaxis (WDEIA). At present, avoidance of wheat products or postprandial rest after ingesting wheat is recommended for patients with WDEIA, depending on the severity [...] Read more.
Immunoglobulin E (IgE)-mediated food allergies to wheat that develop after school age typically shows a type of wheat-dependent exercise-induced anaphylaxis (WDEIA). At present, avoidance of wheat products or postprandial rest after ingesting wheat is recommended for patients with WDEIA, depending on the severity of the allergy symptoms. ω5-Gliadin has been identified as the major allergen in WDEIA. In addition, α/β-, γ-, and ω1,2-gliadins, high and low molecular weight-glutenins, and a few water-soluble wheat proteins have been identified as IgE-binding allergens in a small proportion of patients with IgE-mediated wheat allergies. A variety of approaches have been manufactured to develop hypoallergenic wheat products that can be consumed by patients with IgE-mediated wheat allergies. In order to analyze such approaches, and to contribute to the further improvement, this study outlined the current status of these hypoallergenic wheat productions, including wheat lines with a reduced allergenicity that are mostly constructed for the patients sensitized to ω5-gliadin, hypoallergenic wheat by enzymic degradation/ion exchanger deamidation, and hypoallergenic wheat by thioredoxin treatment. The wheat products obtained by these approaches significantly reduced the reactivity of Serum IgE in wheat-allergic patients. However, either these were not effective on some populations of the patients, or low-level IgE-reactivity to some allergens of the products was observed in the patients. These results highlight some of the difficulties faced in creating hypoallergenic wheat products or hypoallergenic wheat lines through either traditional breeding or biotechnology approaches in developing hypoallergenic wheat completely safe for all the patients allergic to wheat. Full article
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19 pages, 2358 KB  
Article
Idiopathic Anaphylaxis? Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland
by Iwona Poziomkowska-Gęsicka
Int. J. Environ. Res. Public Health 2022, 19(24), 16716; https://doi.org/10.3390/ijerph192416716 - 13 Dec 2022
Cited by 8 | Viewed by 3280
Abstract
The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature [...] Read more.
The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature where as many as 41% of all cases are idiopathic anaphylaxis. Since the introduction of new diagnostic methods such as molecular diagnostics (MD) in our centre, the percentage of idiopathic anaphylaxis in the Anaphylaxis Register has significantly decreased. The purpose of this study was to identify possible causes of idiopathic anaphylaxis in patients with a history of moderate to severe anaphylactic reactions. After using MD, the causative agent was found in another 29 people. The proportion of people with idiopathic anaphylaxis in the Registry decreased from 9.2% to 3.5%. There were no significant differences in the incidence, although men appear to be slightly more common in primary idiopathic anaphylaxis. The mean age of primary idiopathic anaphylaxis was 40 years, but this was as high as 51 for anaphylaxis with alpha-gal allergy. Exercise may or may not be present as a cofactor despite its established role, e.g., in wheat-dependent exercise-induced anaphylaxis (WDEIA). In most of the analyzed cases, i.e., 70%, the reaction took place within an hour. The longest time interval from exposure to the development of symptoms is in the case of alpha-gal allergy; in this analysis, it was at least 5 h after ingestion of the so-called “red meat”. Patients are not aware of the disease, or further attacks cannot be prevented. As many as 80% had idiopathic anaphylaxis prior to visiting the centre, and 80% developed anaphylaxis after visiting the centre, which emphasizes the need to not stop the medical team in their search for the causes. As many as 93% of cases required medical intervention, of which adrenaline was used only in 34.5%, antihistamines in 86%, systemic glucocorticosteroids (sCS) in 75%, and fluids in 62% of cases. A total of 83% of patients received an emergency kit for self-administration. Idiopathic anaphylaxis can be resolved as known-cause anaphylaxis after a thorough medical history and, if possible, without exposing the patient after using appropriate, modern in vitro diagnostic methods, including molecular diagnostics. The diagnosis of idiopathic anaphylaxis should extend the diagnosis to include alpha-gal syndrome, LTP syndrome and WDEIA. Full article
(This article belongs to the Section Environmental Health)
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12 pages, 3025 KB  
Article
Hypoallergenic Wheat Line (1BS-18H) Lacking ω5-Gliadin Induces Oral Tolerance to Wheat Gluten Proteins in a Rat Model of Wheat Allergy
by Yukinori Yamada, Tomoharu Yokooji, Kyohei Kunimoto, Koki Inoguchi, Ryohei Ogino, Takanori Taogoshi, Eishin Morita and Hiroaki Matsuo
Foods 2022, 11(15), 2181; https://doi.org/10.3390/foods11152181 - 22 Jul 2022
Cited by 15 | Viewed by 4376
Abstract
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 [...] Read more.
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. Full article
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11 pages, 581 KB  
Review
Wheat Allergy in Children: A Comprehensive Update
by Giampaolo Ricci, Laura Andreozzi, Francesca Cipriani, Arianna Giannetti, Marcella Gallucci and Carlo Caffarelli
Medicina 2019, 55(7), 400; https://doi.org/10.3390/medicina55070400 - 23 Jul 2019
Cited by 91 | Viewed by 12733
Abstract
Gluten-related disorders are very common in pediatric patients. Wheat allergy is triggered by an immunoglobulin E (IgE)-dependent mechanism; its prevalence varies according to the age and region, and in Europe has been estimated to be lower than 1%. Many studies investigated the potential [...] Read more.
Gluten-related disorders are very common in pediatric patients. Wheat allergy is triggered by an immunoglobulin E (IgE)-dependent mechanism; its prevalence varies according to the age and region, and in Europe has been estimated to be lower than 1%. Many studies investigated the potential role of several external factors that can influence the risk to developing wheat allergy, but results are still inconclusive. It can be responsible for several clinical manifestations depending on the route of allergen exposure: food-dependent exercise-induced anaphylaxis (FDEIA), occupational rhinitis or asthma (also known as baker’s asthma), and contact urticaria. The prognosis of IgE-mediated wheat allergy in children is generally favorable, with the majority of children becoming tolerant by school age. Patients who experienced an anaphylactic reaction prior to 3 years of age and patients with higher level of wheat- or ω-5 gliadin-specific IgE antibodies seem to be at higher risk of persistent wheat allergy. The current management of patients is dietary avoidance. Nowadays, oral immunotherapy has been proposed for wheat allergy with promising results, even if further studies are necessary to establish the best protocol in order to promote tolerance in wheat-allergic children. Full article
(This article belongs to the Special Issue Food Allergies)
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