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Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring.
Laserna-Mendieta, EJ, Casanova, MJ, Arias, Á, Arias-González, L, Majano, P, Mate, LA, Gordillo-Vélez, CH, Jiménez, M, Angueira, T, Tébar-Romero, E, et al
Nutrients. 2020;(1)
Abstract
A lifelong gluten-free diet (GFD) is the only current treatment for celiac disease (CD), but strict compliance is complicated. Duodenal biopsies are the "gold standard" method for diagnosing CD, but they are not generally recommended for disease monitoring. We evaluated the sensitivity and specificity of fecal gluten immunogenic peptides (GIPs) to detect duodenal lesions in CD patients on a GFD and compared them with serum anti-tissue transglutaminase (tTG) IgA antibodies. A prospective study was conducted at two tertiary centers in Spain on a consecutive series of adolescents and adults with CD who maintained a long-lasting GFD. Adherence to a GFD and health-related quality of life were scored with validated questionnaires. Mucosal damage graded according to the Marsh-Oberhüber classification (Marsh 1/2/3) was used as the reference standard. Of the 97 patients included, 27 presented duodenal mucosal damage and 70 had normal biopsies (Marsh 0). The sensitivity (33%) and specificity (81%) of GIPs were similar to those provided by the two assays used to measure anti-tTG antibodies. Scores in questionnaires showed no association with GIP, but an association between GIPs and patients' self-reported gluten consumption was found (p = 0.003). GIP displayed low sensitivity but acceptable specificity for the detection of mucosal damage in CD.
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2.
[Not Available].
Providoli, N
Revue medicale suisse. 2020;(679):235-236
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Allergic reactions to hydrolysed wheat proteins: clinical aspects and molecular structures of the allergens involved.
Tranquet, O, Larré, C, Denery-Papini, S
Critical reviews in food science and nutrition. 2020;(1):147-156
Abstract
Wheat gluten can be chemically or enzymatically hydrolysed to produce functional ingredients useful in food and cosmetics. However severe allergies to hydrolysed wheat proteins (HWP) have been described in Europe and Japan since the early 2000's. Triggering proteins and IgE epitopes were described both for French and Japanese cohorts and appeared remarkably similar leading to define a new wheat allergic entity. Deamidation induced by functionalisation generate neo-allergens responsible for this particular allergy. This article aims to review the processes leading to deamidation and the clinical features of the patients suffering from this allergy. Then the molecular determinants involved in HWP-allergy were exhaustively described and hypothesis regarding the sensitizing mechanism of HWP-allergy are discussed. Finally, current regulation and tools aiming at managing this risk associated with HWP are presented.
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Metabolic effects in patients with celiac disease, patients with nonceliac gluten sensitivity, and asymptomatic controls, after six months of a gluten-free diet.
Remes-Troche, JM, Cobos-Quevedo, OJ, Rivera-Gutiérrez, X, Hernández, G, de la Cruz-Patiño, E, Uscanga-Domínquez, LF
Revista de gastroenterologia de Mexico (English). 2020;(2):109-117
Abstract
INTRODUCTION AND OBJECTIVES It is essential for patients with celiac disease (CD) to be on a gluten-free diet (GFD) but said diet has also been reported to increase the risk for metabolic syndrome. There is no evidence on the metabolic effects of a GFD in patients with nonceliac gluten sensitivity (NCGS) or in asymptomatic subjects. Therefore, the aim of the present study was to evaluate the metabolic effects of a GFD over a 6-month period in patients with CD, patients with NCGS, and in asymptomatic controls (ACs). MATERIALS AND METHODS A prospective study was conducted that evaluated metabolic syndrome and its components of obesity, high blood pressure, hepatic steatosis, and hyperglycemia at the baseline and at 6 months. RESULTS A total of 66 subjects (22 CD, 22 NCGS, and 22 AC) were included in the study. At the baseline, 10% of the patients with CD presented with obesity, high blood pressure, hepatic steatosis, and metabolic syndrome. After 6 months, obesity and metabolic syndrome increased by 20% (p=0.125). In the patients with NCGS, obesity increased by 5% after the GFD and 20% of those patients presented with de novo hepatic steatosis. The prevalence of obesity decreased by 10% in the controls after the GFD (30 vs 20%, p=0.5) and none of the other components of metabolic syndrome were affected. CONCLUSIONS The metabolic benefits and risks of a GFD should be considered when prescribing said diet in the different populations that opt for that type of intervention.
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5.
Pitfalls in the Diagnosis of Coeliac Disease and Gluten-Related Disorders.
Schiepatti, A, Savioli, J, Vernero, M, Borrelli de Andreis, F, Perfetti, L, Meriggi, A, Biagi, F
Nutrients. 2020;(6)
Abstract
The spectrum of gluten-related disorders (GRD) has emerged as a relevant phenomenon possibly impacting on health care procedures and costs worldwide. Current classification of GRD is mainly based on their pathophysiology, and the following categories can be distinguished: immune-mediated disorders that include coeliac disease (CD), dermatitis herpetiformis (DH), and gluten ataxia (GA); allergic reactions such as wheat allergy (WA); and non-coeliac gluten sensitivity (NCGS), a condition characterized by both gastrointestinal and extra-intestinal symptoms subjectively believed to be induced by the ingestion of gluten/wheat that has recently gained popularity. Although CD, DH, and WA are well-defined clinical entities, whose diagnosis is based on specific diagnostic criteria, a diagnosis of NCGS may on the contrary be considered only after the exclusion of other organic disorders. Neither allergic nor autoimmune mechanisms have been found to be involved in NCGS. Mistakes in the diagnosis of GRD are still a relevant clinical problem that may result in overtreatment of patients being unnecessary started on a gluten-free diet and waste of health-care resources. On the basis of our clinical experience and literature, we aim to identify the main pitfalls in the diagnosis of CD and its complications, DH, and WA. We provide a practical methodological approach to guide clinicians on how to recognize and avoid them.
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6.
Negative predictive value of the repeated absence of gluten immunogenic peptides in the urine of treated celiac patients in predicting mucosal healing: new proposals for follow-up in celiac disease.
Ruiz-Carnicer, Á, Garzón-Benavides, M, Fombuena, B, Segura, V, García-Fernández, F, Sobrino-Rodríguez, S, Gómez-Izquierdo, L, Montes-Cano, MA, Rodríguez-Herrera, A, Millán, R, et al
The American journal of clinical nutrition. 2020;(5):1240-1251
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Abstract
BACKGROUND The treatment of celiac disease (CD) is a lifelong gluten-free diet (GFD). The current methods for monitoring GFD conformance, such as a dietary questionnaire or serology tests, may be inaccurate in detecting dietary transgressions, and duodenal biopsies are invasive, expensive, and not a routine monitoring technique. OBJECTIVES Our aim was to determine the clinical usefulness of urine gluten immunogenic peptides (GIP) as a biomarker monitoring GFD adherence in celiac patients and to evaluate the concordance of the results with the degree of mucosal damage. METHODS A prospective observational study was conducted involving 22 de novo CD patients, 77 celiac patients consuming a GFD, and 13 nonceliac subjects. On 3 d of the week, urine samples were collected and the GIP concentrations were tested. Simultaneously, anti-tissue transglutaminase antibodies, questionnaire results, clinical manifestations, and histological findings were analyzed. RESULTS Approximately 24% (18 of 76) of the celiac patients consuming a GFD exhibited Marsh II-III mucosal damage. Among this population, 94% (17 of 18) had detectable urine GIP; however, between 60% and 80% were asymptomatic and exhibited negative serology and appropriate GFD adherence based on the questionnaire. In contrast, 97% (31 of 32) of the celiac patients without duodenal damage had no detectable GIP. These results demonstrated the high sensitivity (94%) and negative predictive value (97%) of GIP measurements in relation to duodenal biopsy findings. In the de novo CD-diagnosed cohort, 82% (18 of 22) of patients had measurable amounts of GIP in the urine. CONCLUSIONS Determining GIP concentrations in several urine samples may be an especially convenient approach to assess recent gluten exposure in celiac patients and appears to accurately predict the absence of histological lesions. The introduction of GIP testing as an assessment technique for GFD adherence may help in ascertaining dietary compliance and to target the most suitable intervention during follow-up.
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Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.
Barbaro, MR, Cremon, C, Wrona, D, Fuschi, D, Marasco, G, Stanghellini, V, Barbara, G
Nutrients. 2020;(12)
Abstract
Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.
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Pilot study on non-celiac gluten sensitivity: effects of Bifidobacterium longum ES1 co-administered with a gluten-free diet.
Di Pierro, F, Bergomas, F, Marraccini, P, Ingenito, MR, Ferrari, L, Vigna, L
Minerva gastroenterologica e dietologica. 2020;(3):187-193
Abstract
BACKGROUND Bifidobacterium longum ES1 is a strain probiotic, colonizing the human gut and capable of a degradative action on gliadin. In an attempt to find new nutritional solutions aimed at improving the quality of life of patients with non-celiac gluten sensitivity (NCGS) we evaluated the effectiveness of this strain, in association with a gluten-free diet, comparing its efficacy versus diet therapy alone. METHODS The experimental design included a non-randomized, open-label, 1:1 intervention study in parallel groups. Enrolled patients with symptoms attributable to NCGS, and with negative diagnoses of both wheat allergy and celiac disease, were included in this three-month trial divided into four outpatient visits (baseline, T1, T2 and T3). Fifteen patients for each group completed the experimental protocol. RESULTS Our results showed that a combination of diet and probiotic determined a more significant reduction in the frequency and intensity of intestinal and extra-intestinal symptoms, and a clear improvement in stool consistency. CONCLUSIONS Although the study was carried out on a small number of patients, the results of our pilot trial suggest that a combined strategy of naturally gluten-free diet therapy with administration of the probiotic strain ES1 appears to offer a greater advantage than the dietary regime alone in improving the clinical symptomatic picture and in stabilizing the intestinal microbiota.
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Effects of edible plant polyphenols on gluten protein functionality and potential applications of polyphenol-gluten interactions.
Girard, AL, Awika, JM
Comprehensive reviews in food science and food safety. 2020;(4):2164-2199
Abstract
Expanding plant-based protein applications is increasingly popular. Polyphenol interactions with wheat gluten proteins can be exploited to create novel functional foods and food ingredients. Polyphenols are antioxidants, thus generally decrease gluten strength by reducing disulfide cross-linking. Monomeric polyphenols can be used to reduce dough mix time and improve flexibility of the gluten network, including to plasticize gluten films. However, high-molecular-weight polyphenols (tannins) cross-link gluten proteins, thereby increasing protein network density and strength. Tannin-gluten interactions can greatly increase gluten tensile strength in dough matrices, as well as batter viscosity and stability. This could be leveraged to reduce detrimental effects of healthful inclusions, like bran and fiber, to loaf breads and other wheat-based products. Further, the dual functions of tannins as an antioxidant and gluten cross-linker could help restructure gluten proteins and improve the texture of plant-based meat alternatives. Tannin-gluten interactions may also be used to reduce inflammatory effects of gluten experienced by those with gluten allergies and celiac disease. Other potential applications of tannin-gluten interactions include formation of food matrices to reduce starch digestibility; creation of novel biomaterials for edible films or medical second skin type bandages; or targeted distribution of micronutrients in the digestive tract. This review focuses on the effects of polyphenols on wheat gluten functionality and discusses emerging opportunities to employ polyphenol-gluten interactions.
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Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease.
Goel, G, Daveson, AJM, Hooi, CE, Tye-Din, JA, Wang, S, Szymczak, E, Williams, LJ, Dzuris, JL, Neff, KM, Truitt, KE, et al
Clinical and experimental immunology. 2020;(1):68-78
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Abstract
Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on a gluten free-diet (n = 25) and from a parallel cohort of healthy volunteers (n = 25) who underwent an unmasked gluten challenge. Sera were collected at baseline and 2, 4 and 6 h after consuming 10 g vital wheat gluten flour; 187 cytokines were assessed. Confirmatory analyses were performed by high-sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, chemokine (C-C motif) ligand 20 (CCL20), IL-6, chemokine (C-X-C motif) ligand (CXCL)9, CXCL8, interferon (IFN)-γ, IL-10, IL-22, IL-17A, tumour necrosis factor (TNF)-α, CCL2 and amphiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at 4 h. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had the highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their probable source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.