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Recent Advances in Gluten-Related Disorders
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Recent Advances in Gluten-Related Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 3240

Special Issue Editor

Dr. Sylwia Smolińska

E-Mail Website
Guest Editor
Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland
Interests: gastrointestinal track; histamine; gut microbiome; clinical immunology; allergy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nowadays, the consumption of gluten-free products is becoming an increased alimentary habit in the general population. An increased number of people are encouraged to view gluten as a toxic compound, a huge impact of which has been the fashion of being on a gluten-free diet, which is popularized by celebrities without medical or scientific backgrounds. The suggestion that the avoidance of gluten improves health causes a medically unjustified adherence to a gluten-free diet. Gluten is the main storage protein of wheat grains. Gluten is a complex mixture of hundreds of related but distinct proteins, mainly gliadin and glutenin. Similar storage proteins exist, such as secalin in rye, hordein in barley, and avenins in oats, and are collectively referred to as "gluten". I welcome you to participate in this Special Issue and the discussion about the importance of gluten-rich food, such as grains (wheat, rye, barley, and oats), as important staple food in the daily diet and its necessary avoidance in gluten-related disorders, such as celiac disease, non-celiac gluten sensitivity (NCGS), and wheat allergy. In my opinion, it should still be a matter of active debate in the scientific community, especially to show the importance of gluten intake as well as to show the only medical reasons of its avoidance. All papers describing the most recent advances in the immunopathology of gluten digestion, the diagnostic biomarkers of gluten-related diseases, the susceptibility of gluten-related disorders, and the new potential therapies for the treatment of gluten-related disorders, as well as papers that show the importance of gluten intake in the daily diet, are more than welcome to be submitted.

Dr. Sylwia Smolińska
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gluten
  • gluten-free diet
  • gluten-rich diet
  • celiac disease
  • wheat allergy
  • non-celiac gluten sensitivity

Published Papers (4 papers)

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Research

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15 pages, 2036 KiB  
Article
Detection of Sensitization Profiles with Cellular In Vitro Tests in Wheat Allergy Dependent on Augmentation Factors (WALDA)
by Valentina Faihs, Viktoria Schmalhofer, Claudia Kugler, Rebekka K. Bent, Katharina A. Scherf, Barbara Lexhaller, Charlotte G. Mortz, Carsten Bindslev-Jensen, Tilo Biedermann, Per S. Skov, Bernadette Eberlein and Knut Brockow
Int. J. Mol. Sci. 2024, 25(7), 3574; https://doi.org/10.3390/ijms25073574 - 22 Mar 2024
Viewed by 524
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Advances in Gluten-Related Disorders)
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18 pages, 7811 KiB  
Article
Specificity Enhancement of Glutenase Bga1903 toward Celiac Disease-Eliciting Pro-Immunogenic Peptides via Active-Site Modification
by Yu-You Liu, Rui-Ling Ye and Menghsiao Meng
Int. J. Mol. Sci. 2024, 25(1), 505; https://doi.org/10.3390/ijms25010505 - 29 Dec 2023
Viewed by 698
Abstract
Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous [...] Read more.
Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicates its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 34-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. The increased specificity of E380Q/S387L not only enhances its ability to break down pro-immunogenic peptides but also positions this enzyme variant as a promising candidate for oral therapy for celiac disease. Full article
(This article belongs to the Special Issue Recent Advances in Gluten-Related Disorders)
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20 pages, 2577 KiB  
Article
Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis
by Rick Jorgensen, Haoran Gao, Tamil Selvan Arul Arasan, Chris Van Antwerp, Vaisheswini Sundar, Perry K. W. Ng and Venu Gangur
Int. J. Mol. Sci. 2023, 24(24), 17247; https://doi.org/10.3390/ijms242417247 - 08 Dec 2023
Cited by 1 | Viewed by 920
Abstract
Wheat is a prominent allergenic food that can trigger life-threatening anaphylaxis. Presently, it remains unclear whether wheat glutenin (WG) extract possesses inherent sensitization potential independently, without the use of adjuvants, and whether it can sensitize mice to the extent of inducing life-threatening systemic [...] Read more.
Wheat is a prominent allergenic food that can trigger life-threatening anaphylaxis. Presently, it remains unclear whether wheat glutenin (WG) extract possesses inherent sensitization potential independently, without the use of adjuvants, and whether it can sensitize mice to the extent of inducing life-threatening systemic anaphylaxis. In this study, we tested the hypothesis that repeated skin exposures to WG extract without adjuvant will sensitize mice with the resultant anaphylactic reaction upon systemic WG challenge. Balb/c mice were bred and maintained on a strict plant protein-free diet and were repeatedly exposed to a WG extract or vehicle once a week for 9 weeks. WG-specific (s)IgE and total (t)IgE levels were quantified. Mice were challenged with WG extract to induce anaphylactic reactions as measured by hypothermic shock response (HSR) and mucosal mast cell degranulation response (MMCR). We also conducted proteomic analysis of 120 spleen immune markers. These skin-sensitized mice exhibited exposure-dependent IgE responses and near-fatal anaphylaxis upon challenge. Proteomic analysis identified seven dramatically elevated immune biomarkers in anaphylactic mice. These data reveal that WG is intrinsically allergenic, and that chronic skin exposure to WG extract can prime the mice for potentially fatal anaphylaxis. Full article
(This article belongs to the Special Issue Recent Advances in Gluten-Related Disorders)
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Review

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19 pages, 1210 KiB  
Review
Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development
by Rick Jorgensen, Shambhavi Shivaramaiah Devarahalli, Yash Shah, Haoran Gao, Tamil Selvan Arul Arasan, Perry K. W. Ng and Venugopal Gangur
Int. J. Mol. Sci. 2024, 25(8), 4399; https://doi.org/10.3390/ijms25084399 - 16 Apr 2024
Viewed by 463
Abstract
Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive [...] Read more.
Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future. Full article
(This article belongs to the Special Issue Recent Advances in Gluten-Related Disorders)
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