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.

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.

UNASSIGNED: 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.
UNASSIGNED: We aimed to execute an extensive bibliometric study, focusing on the past 30 years of literature related to wheat allergy.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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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.

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.

UNASSIGNED: This study aimed to determine the prevalence and criteria of wheat allergy (WA) among patients with resistant allergic conjunctivitis (AC).
UNASSIGNED: A prospective comparative study was conducted on 100 patients with resistant AC. Skin prick-tests (SPTs), total and sIgE against a panel of inhalant and food allergens were performed in all patients\' sera. They were divided into 2 groups according to skin prick test (SPT) and specific IgE (sIgE) level, namely the wheat sensitive group (WSG) and wheat tolerant group (WTG). Total ocular symptom scores (TOSS) and 4-point sign scales were correlated for both groups.
UNASSIGNED: Ten patients out of 100 with IgE-mediated resistant AC were wheat sensitive, and the other 90 were wheat tolerant patients. WSG included patients of significantly younger age. Positive family history of atopy was proven in 100% of WSG vs. 67% of WTG. A significantly higher frequency of multiorgan allergy was detected in 100% of WSG vs. 20% in WTG (P = 0.0001). Thirty (30%) of WSG had associated allergic rhinitis (AR) and bronchial asthma (BA). Another 30% had an associated AR only, 10% had an associated BA only, and another 20% had an associated skin allergy. TOSS, 4- point sign scale, and total IgE level were significantly higher in WSG.
UNASSIGNED: This study provides novel evidence that wheat allergy is responsible for some severe forms of AC.

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.

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.

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.