Concept: Triticeae glutens
Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.
Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy and production of several autoantibodies of which endomysial, tissue transglutaminase and deamidated gliadin peptide antibodies are considered specific. Although anti-reticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This review highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.
BACKGROUND: Common marmosets (Callithrix jacchus) are susceptible to gastrointestinal diseases. Sensitivity to nutritional elements, for example gluten, has been suggested, but a serological screening has not been performed yet. METHODS: A gluten-containing diet was offered to 24 animals, followed by a gluten-free diet. During these diets, serum IgA antibodies to gliadin (AGA), tissue transglutaminase (tTG), deamidated gliadin (ADGA), and glycoprotein 2 (AGP2A) were determined. Body weight, diarrhea, and other clinical symptoms were recorded. RESULTS: Gluten increased AGA, tTG, and AGP2A concentrations in 13 of 24 animals. A significant decline of AGA and AGP2A was seen on gluten withdrawal. Positive (AGA, tTG) animals presented diarrhea more frequently on gluten-containing diet and showed significantly increased body weight on gluten-free diet compared to negative animals. CONCLUSION: Gluten ingestion caused gastrointestinal symptoms in common marmosets, which disappeared on gluten withdrawal. Considering the immunological response to both diets, gluten sensitivity seems to be most likely.
Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD).
To describe the clinical, serologic, and histologic characteristics of children with gluten sensitivity (GS).
Although no biomarker has been identified to date, previous studies have reported that about 50% of patients with suspected Non Celiac Gluten Sensitivity (NCGS) had positive first generation anti- gliadin antibodies (AGAs), expecially of the IgG class. These antibodies are not specific for NCGS, being also found in CD (80-90%), autoimmune liver disorders (21.5%), connective tissue disease (9%) and IBS (20%), as well as in healthy controls (2-8%), but their finding in patients with a clinical phenotype consistent with NCGS has been regarded as an element supporting this diagnosis. Even if the correlation between AGA IgG and NCGS condition turned out to be statistically significant in most studies, AGA IgG doesn’t seem to be an adequately strong marker for its lacking diagnostic accuracy. However it can partly help the NCGS diagnosis, integrated in the overall management of the patient. Therefore, in the presence of clinical symptoms that suggest NCGS, IgG AGA positivity, together with negative anti-tTG, EMA, and anti deamidated gliadin peptides (DGP) antibodies, NCGS diagnosis might be suspected. Future researches are necessary to identify reliable biomarkers for NGCS diagnosis and to better define clinically and serologically NCGS patients.
The first competitive disposable amperometric immunosensor based on gliadin-functionalized carbon/nanogold screen-printed electrodes was developed for rapid determination of celiotoxic prolamins. To date, no competitive spectrophotometric or electrochemical immunoassays have yet been successfully applied to gluten detection in processed food samples, which require the use of complex prolamin extraction solutions containing additives with denaturing, reducing and disaggregating functions. Thus, in this work, great effort was put into the optimization and performance evaluation of the immunosensor in terms of suitability as a screening tool for analysis of cereal-based food samples. For this purpose, aqueous ethanol or complex extraction mixtures, as the patented Cocktail Solution®, were proved effective in the extraction of gliadin. Good sensitivity was achieved after optimization of the immunocompetitive assay, giving limit of detection and limit of quantitation of 8 and 22 ng/ml of gliadin, respectively, for ethanol extracts. The immunosensor was proved to be suitable also for samples extracted with Cocktail Solution® after a proper dilution. Analysis of real samples of different flours proved the suitability of the immunosensing device as a powerful tool for safety assessment of raw materials used for the formulation of dietary products for celiac disease patients. This immunosensor combines good analytical performance using a very simplified set-up protocol with suitability for rapid screening analysis performed using inexpensive and portable instrumentation. Graphical abstract Depiction of the development and working principle of the competitive immunosensor.
Dermatitis herpetiformis (DH) is intensely pruritic papulovesicular skin disease, and is considered to be a cutaneous manifestation of gluten sensitivity; i.e., an extra-intestinal presentation of celiac disease (CD).(1) The processing of the dietary gluten antigen (gliadin) requires HLA-DQ2 or HLA-DQ8,(2) and approximately 85% of Caucasian DH patients carry human leukocyte antigen (HLA)-DQ2 and the majority of the remaining cases carry HLA-DQ8.(3) Tissue transglutaminase (tTG) (transglutaminase 2; TG2) is the major autoantigen in CD,(1) whereas epidermal transglutaminase (eTG) (transglutaminase 3; TG3) is the major autoantigen in DH. This article is protected by copyright. All rights reserved.
- Current opinion in clinical nutrition and metabolic care
- Published over 3 years ago
Noncoeliac gluten sensitivity (NCGS) has gained attention as an emerging clinical entity. Data regarding the epidemiology, pathogenesis, and management of NCGS are scattered in view of the diagnostic uncertainty surrounding the disorder. We aim to provide a current perspective of NCGS and its associated controversies.
High selectivity of genosensors is crucial for certain applications such as those involving species with high genetic variability. This is an unresolved problem when dealing with long target sequences that is further complicated when the target contains repetitive sequence domains. As a model for this situation, the problem of detecting gluten in food with identification of the source is studied. In order to discriminate the specific DNA sequence that encodes the wheat prolamin (gliadin) from rye and barley prolamins, the exquisite selectivity of a rationally designed hairpin capture probe is proposed and compared to a nonstructured capture probe. An electrochemical sandwich assay is proposed, involving capture probes chemisorbed on Au surfaces and biotinylated-signaling probes in combination with streptavidin-peroxidase labeling conjugates. As a result, a genosensor with similar sensitivity to that observed with linear probes but with complete specificity against closely related species was achieved. The surface-attached DNA stem-loop yields a device capable of accurately discriminating wheat DNA from rye and barley with a limit of detection of 1 nM.