ArticleLiterature Review

Non-celiac Gluten Sensitivity

October 2012
Gastrointestinal Endoscopy Clinics of North America 22(4):723-34

DOI:10.1016/j.giec.2012.07.006

Source
PubMed

Authors:

University of Oslo

Gluten sensitivity has been best recognized and understood in the context of two conditions, celiac disease and wheat allergy. However, some individuals complain of symptoms in response to ingestion of "gluten," without histologic or serologic evidence of celiac disease or wheat allergy. The term non-celiac gluten sensitivity (NCGS) has been suggested for this condition, although a role for gluten proteins as the sole trigger of the associated symptoms remains to be established. This article reviews the available information regarding symptomatology, epidemiology and genetics, serology and histology, and in vitro and in vivo experimental data on the pathophysiology of NCGS.

ANALYSIS OF NON-CELIAC GLUTEN SENSITIVITY IN PATIENTS WITH ENDOMETRIOSIS

Article

Jul 2021

Overview and Aims: Identify patients with surgically confirmed endometriosis and with gastrointestinal symptomatology by assessing whether there is clinical improvement of these from the adoption of gluten-free diet (GFD). Study design: They were invited to participate in the study by the researchers through telephone calls and instant messaging applications after selection in the clinics of attending physicians. Population: Through the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire, the relationship of GFD adherence to symptomatology attenuation and benefit in the quality of life of 48 patients was analyzed. Methods: Inclusion criteria: female patients with surgical confirmation of endometriosis who agreed to participate in the study in accordance with the Informed Consent Form (ICF). Exclusion criteria: patients who already performed GFD, patients diagnosed with celiac disease, gluten allergy or non-celiac sensitivity to gluten, presence of gastrointestinal comorbidities, severe diseases or cognitive alterations that prevented the study from being performed. The patients who obtained the top 20 scores were invited to adopt GFD for one month, among those selected, only 12 proposed to participate in the diet. However, three of these presented personal complications that prevented the continuation of the same. After this period, a new questionnaire was applied to measure the impact of the diet on quality of life. Results: Nine patients finished the proposed period for the diet, with the average score obtained in the pre-diet questionnaire reducing from 57.2 to 36 in the post-diet. Conclusion: There was an improvement in gastrointestinal complaints of most patients and consequently in quality of life with GFD.

Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity

Article

Full-text available

Nov 2017
GASTROENTEROLOGY

Background & aims: Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in absence of celiac disease. The mechanisms of non-celiac gluten sensitivity are unclear, and there are no biomarkers for this disorder. Foods with gluten often contain fructans, a type of fermentable oligo-, di-, monosaccharides and polyols. We aimed to investigate the effect of gluten and fructans separately in individuals with self-reported gluten sensitivity. Methods: We performed a double-blind crossover challenge of 59 individuals on a self-instituted gluten-free diet, for whom celiac disease had been excluded. The study was performed at Oslo University Hospital in Norway from October 2014 through May 2016. Participants were randomly assigned to groups placed on diets containing gluten (5.7 g), fructans (2.1 g), or placebo, concealed in muesli bars, for 7 days. Following a minimum 7-day washout period (until the symptoms induced by the previous challenge were resolved), participants crossed over into a different group, until they completed all 3 challenges (gluten, fructan, and placebo). Symptoms were measured by gastrointestinal symptom rating scale irritable bowel syndrome (GSRS-IBS) version. A linear mixed model for analysis was used. Results: Overall GSRS-IBS scores differed significantly during gluten, fructan, and placebo challenges; mean values were 33.1±13.3, 38.6±12.3, and 34.3±13.9, respectively (P = .04). Mean scores for GSRS bloating were 9.3±3.5, 11.6±3.5, and 10.1±3.7, respectively, during the gluten, fructan, and placebo challenges (P = .004). The overall GSRS-IBS score for participants consuming fructans was significantly higher than for participants consuming gluten (P = .049), as was the GSRS bloating score (P = .003). Thirteen participants had the highest overall GSRS-IBS score after consuming gluten, 24 had the highest score after consuming fructan, and 22 had the highest score after consuming placebo. There was no difference in GSRS-IBS scores between gluten and placebo groups. Conclusions: In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the gastrointestinal symptom rating scale irritable bowel syndrome version.Clinicaltrials.gov no: NCT02464150.

The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma

Article

Full-text available

Dec 2015

The spectrum of gluten-related disorders has widened in recent times and includes celiac disease, non-celiac gluten sensitivity, and wheat allergy. The complex of symptoms associated with these diseases, such as diarrhea, constipation or abdominal pain may overlap for the gluten related diseases, and furthermore they can be similar to those caused by various other intestinal diseases, such as irritable bowel syndrome (IBS). The mechanisms underlying symptom generation are diverse for all these diseases. Some patients with celiac disease may remain asymptomatic or have only mild gastrointestinal symptoms and thus may qualify for the diagnosis of IBS in the general clinical practice. Similarly, the overlap of symptoms between IBS and non-celiac gluten sensitivity (NCGS) often creates a dilemma for clinicians. While the treatment of NCGS is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. Both IBS and NCGS are common in the general population and both can coexist with each other independently without necessarily sharing a common pathophysiological basis. Although the pathogenesis of NCGS is not well understood, it is likely to be heterogeneous with possible contributing factors such as low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Innate immunity may also play a pivotal role. One possible inducer of innate immune response has recently been reported to be amylase-trypsin inhibitor, a protein present in wheat endosperm and the source of flour, along with the gluten proteins.

Resetting Policies to End Family Homelessness

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Apr 2020

Homelessness is a devastating experience for children and their families. Families, the majority of whose members are children, now comprise more than one-third of the overall homeless population. Most of these children are less than six years old. Various assumptions have driven policy and the allocation of resources to programs serving these families. Although decades of research and field experience suggest strategies for preventing and reducing this problem, perspectives differ, hindering the development of effective solutions. In this article, we explore some of these assumptions, including ( a) definitions of homelessness used to count the numbers of families and determine resource allocation, ( b) the needs of children and responses to the impact of adverse childhood experiences, and ( c) whether services matter and should be integrated with affordable housing. We conclude by suggesting various directions to ensure that these children are protected and have the opportunity to grow and thrive. Expected final online publication date for the Annual Review of Public Health, Volume 41 is April 1, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Review paper. Gluten-related disorders and schizophrenia - potential linking mechanisms, diagnostic and therapeutic challenge

Article

Full-text available

Jan 2017

More and more evidence confirms the theory that the intake of cereal products containing gluten may play an important role in the pathogenesis of many diseases. There are also premises indicating the relationship between the so-called gluten-related diseases and the development and course of mental disorders, including schizophrenia. The aim of this article is to review the literature on the potential relationship between the consumption of gluten and schizophrenia, considering the etiopathogenesis and the role of gluten-free diet in the treatment of schizophrenia. Methods: There were analysed available research papers in PubMed and Google Scholar with the key words: schizophrenia, gluten- related disorders, allergy to grain products, celiac disease, microbiota, immune system, exorphins and time span: 1960-2016 . Conclusions: Existing research results indicate a possible relationship between diet rich in grain products with high gluten content and the occurrence or exacerbation of schizophrenia symptoms. However, further studies are necessary to: 1) identify groups of patients for whom the consumption of cereal products (gluten) is associated with a particular risk of schizophrenia exacerbation, 2) determine the mechanisms relating the consumption of gluten with the mental state of schizophrenic patients, 3) get the possible benefits of implementing gluten-free diet in patients with schizophrenia.

Changes in the coelomic microclimate during carbon dioxide laparoscopy: Morphological and functional implications

Article

Mar 2017

Robert Beaumont Wilson

In this article the adverse effects of laparoscopic CO2 pneumoperitoneum and coelomic climate change, and their potential prevention by warmed, humidified carbon dioxide insufflation are reviewed. The use of pressurized cold, dry carbon dioxide (C02) pneumoperitoneum causes a number of local effects on the peritoneal mesothelium, as well as systemic effects. These can be observed at a macroscopic, microscopic, cellular and metabolic level. Local effects include evaporative cooling, oxidative stress, desiccation of mesothelium, disruption of mesothelial cell junctions and glycocalyx, diminished scavenging of reactive oxygen species, decreased peritoneal blood flow, peritoneal acidosis, peritoneal hypoxia or necrosis, exposure of the basal lamina and extracellular matrix, lymphocyte infiltration, and generation of peritoneal cytokines such as IL-1, IL-6, IL-8 and TNFα. Such damage is increased by high CO2 insufflation pressures and gas velocities and prolonged laparoscopic procedures. The resulting disruption of the glycocalyx, mesothelial cell barrier and exposure of the extracellular matrix creates a cascade of immunological and pro-inflammatory events and favours tumour cell implantation. Systemic effects include cardiopulmonary and respiratory changes, hypothermia and acidosis. Such coelomic climate change can be prevented by the use of lower insufflation pressures and preconditioned warm humidified CO2. By achieving a more physiological temperature, pressure and humidity, the coelomic microenvironment can be better preserved during pneumoperitoneum. This has the potential clinical benefits of maintaining isothermia and perfusion, reducing postoperative pain, preventing adhesions and inhibiting cancer cell implantation in laparoscopic surgery.

Non-celiac gluten sensitivity: approaches to differential diagnosis and potential biomarkers

Article

Full-text available

Jan 2023

The aim of this review was to highlight current approaches to the diagnosis of non-celiac gluten sensitivity. A literature search was performed in PubMed, NCBI (National Library of Medicine), Scopus, and Embase databases using the following key words: “non-celiac gluten sensitivity”, “non-celiac wheat sensitivity” combined with “diagnostics”, “biomarkers”. The selection criteria used were English, human research, and clinical trials. Only articles published in peer-reviewed journals were included in the study. The disadvantages of the currently available diagnostic protocol, a double-blind, placebo-controlled study, were presented, among them the difficulties of differential diagnosis in the first step and the problems of gluten provocation in the second. Potential biomarkers were introduced, the determination of which may eventually become an alternative to the current approach. Key words: celiac disease, gluten intolerance, non-celiac gluten sensitivity, wheat allergy, gluten

Role of Nutrition in Gastroesophageal Reflux, Irritable Bowel Syndrome, Celiac Disease, and Inflammatory Bowel Disease

Article

Jul 2023

There remains a paucity of data on the efficacy of nutritional interventions in luminal gastrointestinal disorders. This review appraises the evidence supporting dietary modification in gastroesophageal reflux disease (GERD), irritable bowel syndrome, Celiac disease, and inflammatory bowel disease. Alhough the use of elimination diets; high fat/low carb; low fermentable oligosaccharides, disaccharides, monosaccharides and polyols; and lactose-free diets in GERD have been studied, the evidence supporting their efficacy remains weak and mixed. Patients with GERD should avoid eating within 3 hours of lying recumbent. Studied dietary interventions for disorders of gut-brain interaction include low fermentable oligosaccharides, disaccharides, monosaccharides and polyols and gluten-restricted and lactose-free diets. While all can be effective in carefully, individually selected patients, the evidence for each intervention remains low. In patients with inflammatory bowel disease, enteral nutrition is established in pediatric populations as useful in reducing inflammation and partial enteral nutrition has a growing evidence base for use in adults and children. Specific carbohydrate diets and the Crohn’s disease exclusion diet show promising evidence but require further study to validate their efficacy prior to recommendation. Overall, the evidence supporting nutritional therapy across luminal gastrointestinal disorders is mixed and often weak, with few well-designed randomized controlled trials (RCTs) demonstrating consistent efficacy of interventions. RCTs, particularly cross-over RCTs, show potential to compare dietary interventions.

Non-celiac gluten sensitivity in pediatrics

Article

Full-text available

Jun 2023

The possibility of a causal relationship between gluten intake and the development of symptoms in the absence of celiac disease (CD) and wheat allergy (WA) has recently gained new scientific interest and includes a condition known as non-celiac gluten sensitivity (NCGS). To date, NCGS has been widely described in adults, whereas there is little information about this pathology in pediatric practice. This article presents a clinical case of NCGS in a 6-year-old girl who was admitted to the gastroenterology department of the Republican Specialized Scientific and Practical Medical Center of Pediatrics (Republic of Uzbekistan) with complaints of abdominal pain, bloating, weight loss, liquid stools, headaches, and fatigue. The complaints appeared 5 months before hospitalization. Antibodies to tissue transglutaminase IgA were within reference ranges, specific IgE antibodies to wheat and gluten were not elevated. A biopsy from the distal duodenum revealed Marsh-Oberhuber 1 lesions. The patient was switched to a gluten-free diet (GFD) with suspected NCGS. At week 4 of the diet, an improvement was noted, but abdominal bloating persisted. An intolerance to components such as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) was suspected. The use of the FODMAP diet significantly improved the condition. The reintroduction of gluten after 6 weeks resulted in a recurrence of symptoms, confirming the diagnosis of NCGS. Given that the number of gluten-related diseases is increasing, and not much is known about NCGS, we decided to present this case to raise awareness and questions regarding diagnosis, the need for specific monitoring, and treatment. Key words: FODMAP, gluten, children, non-celiac gluten sensitivity, celiac disease

Non-celiac gluten sensitivity as a rare cause of growth retardation in children: a case series study

Article

Full-text available

Oct 2021

Aim: Herein, we present five children and adolescents with a final diagnosis of non-celiac gluten sensitivity (NCGS). Background: Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extra-intestinal symptoms triggered by ingestion of gluten-containing compounds, e.g., wheat, rye, and barley, in subjects without celiac disease or wheat allergy. Methods: Demographic characteristics, clinical manifestations, serum biomarkers and skin prick test were evaluated. Patient data was also recorded after they followed a gluten-free diet (GFD). Height and weight were measured, and all patients were examined 6 months after following the suggested GFD. Results: All patients had failure to thrive and abdominal pain. Clinical symptoms were reduced, and significant weight and height gains were detected after 1 month of following a gluten-free diet. Conclusion: The relationship between failure to thrive (FTT) and NCGS is still unknown; hence, NCGS may be one of the main causes of FTT which can be prevented by gluten-free diets.

Type 1 Marsh Celiac Disease: Diagnosis and Response

Chapter

Nov 2014

Les dosages d’IgG anti aliments méthodes et pertinence clinique des résultats. Position du groupe de travail de biologie de la Société française d’allergologie

Article

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Apr 2018

De plus en plus de personnes dans les pays développés attribuent à une intolérance alimentaire diverses manifestations cliniques de typestroubles gastro-intestinaux, douleurs articulaires voire polyarthrite rhumatoïde (PR), migraine ou fatigue chronique. Plusieurs auteurs ont rapportéune fréquence plus importante de la positivité des IgG anti-aliments chez les patients souffrant de syndrome de l’intestin irritable (SII), de maladiesinflammatoires chroniques de l’intestin (MICI) ou de PR comparés aux témoins sains. Depuis une décennie, ces dosages de recherche sontdisponibles en routine sur prescription médicale mais aussi en accès libre sans avis médical via internet. Ces dosages sont utilisés pour établir desrégimes d’éviction des aliments pour lesquels la recherche d’IgG est positive, dans l’espoir d’une amélioration des symptômes supposés être enrelation avec la consommation de ces aliments par le biais d’une réaction d’intolérance faisant intervenir les IgG. L’objectif de ce travail est derappeler les mécanismes impliqués dans les intolérances et allergies alimentaires, et le rôle physiologique des réponses immunitaires à IgG. Lestechniques de dosage des IgG anti-aliments commercialement disponibles sont passées en revue. Les principales études basées sur le dosage desIgG anti-aliments appliqué à diverses pathologies font l’objet d’une analyse critique, suivie d’une discussion. Il en ressort que l’intérêt clinique desdosages d’IgG anti-aliments est l’objet d’une vive polémique en raison de leur mauvaise valeur prédictive positive. Les recommandations établiessur la base de ces dosages sont susceptibles de faire prendre un risque au patient en retardant quelquefois le bon diagnostic ou en lui faisant suivreun régime alimentaire d’éviction le plus souvent inutile et parfois délétère pour sa santé. Les coûts directs liés aux dosages et indirects occasionnéspar les régimes d’éviction, souvent élevés, peuvent être évités au profit d’autres stratégies diagnostiques. En conclusion, dans l’état actuel des connaissances médicales, les dosages d’IgG anti-aliments ne devraient plus être pratiqués en routine pour établir un diagnostic d’intolérance ouallergie alimentaire à IgG, ni mettre en place un régime d’éviction. Leur utilisation devrait être réservée à des fins de recherche.

Les dosages d’IgG anti-aliments : méthodes et pertinence clinique des résultats. Position du groupe de travail de biologie de la Société française d’allergologie

Article

Apr 2018

An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity

Article

Full-text available

Dec 2019
PLOS ONE

Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease.

Edible Brown Seaweed in Gluten-Free Pasta: Technological and Nutritional Evaluation

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Nov 2019

Seaweed is a novel source of important nutritional compounds with interesting biological activities that could be processed into added-value products, namely gluten-free foods. In this study, two previously developed products obtained from Laminaria ochroleuca processing (liquid extract and a purée-like mixture) were incorporated in gluten-free (GF) pasta in order to develop functional products especially designed for the celiac population. The raw and cooked pastas were characterized in terms of their cooking quality parameters, nutritional composition, texture and rheological properties, and antioxidant activity. It was found that the developed GF pastas had similar mechanical and texture characteristics to the control. Both supplemented GF pastas presented a significantly (p < 0.05) higher fibre and mineral content than the control pasta.

Anti-food IgG assays: Methods and clinical relevance of results. Position of the biology task force of the French society of allergy

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Jan 2018

Autoantibodies in the Extraintestinal Manifestations of Celiac Disease

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Aug 2018

Increased antibody reactivity towards self-antigens is often indicative of a disruption of homeostatic immune pathways in the body. In celiac disease, an autoimmune enteropathy triggered by the ingestion of gluten from wheat and related cereals in genetically predisposed individuals, autoantibody reactivity to transglutaminase 2 is reflective of the pathogenic role of the enzyme in driving the associated inflammatory immune response. Autoantibody reactivity to transglutaminase 2 closely corresponds with the gluten intake and clinical presentation in affected patients, serving as a highly useful biomarker in the diagnosis of celiac disease. In addition to gastrointestinal symptoms, celiac disease is associated with a number of extraintestinal manifestations, including those affecting skin, bones, and the nervous system. Investigations of these manifestations in celiac disease have identified a number of associated immune abnormalities, including B cell reactivity towards various autoantigens, such as transglutaminase 3, transglutaminase 6, synapsin I, gangliosides, and collagen. Clinical relevance, pathogenic potential, mechanism of development, and diagnostic and prognostic value of the various identified autoantibody reactivities continue to be subjects of investigation and will be reviewed here.

Recommandations de bonne pratique de prescription et d’interprétation de la biologie de l’allergie : démarche méthodologique d’actualisation 2018 par le groupe de travail de la Société française d’allergologie

Article

Full-text available

Apr 2018

Introduction Les examens biologiques sont d’un apport important pour le diagnostic et le suivi des allergies ou la recherche de facteurs prédisposant à celles-ci. L’utilisation optimisée de ces outils nécessite une actualisation constante des connaissances. En France, le texte de recommandations de la Haute Autorité de santé (HAS) date de 2005. La mise à disposition des allergènes moléculaires et l’évolution des stratégies diagnostiques a rendu indispensable une actualisation de ces recommandations, qui a été initiée sous l’impulsion de la Société française d’allergologie. Méthodes Nous avons utilisé la méthode de Recommandation pour la pratique clinique (RPC) élaborée par la HAS pour rédiger des recommandations concises, gradées par niveaux de preuve, répondant aux questions posées. Ces recommandations ont été relues par un groupe de relecture incluant les professionnels et usagers concernés, puis validées par un groupe de validation. Les liens d’intérêt des rédacteurs ont été déclarés selon les exigences de la HAS. Résultats Nous avons identifié 63 questions, objet de ces recommandations de bonne pratique, dont 11 sur les allergies respiratoires, 28 sur les allergies alimentaires, 11 sur les allergies aux médicaments, 8 sur les allergies aux piqûres et morsures d’arthropodes et 5 sur d’autres pathologies allergiques. La majorité des recommandations relèvent d’un niveau de preuve de grade C. Un préambule aborde 16 questions d’ordre plus général, liées à la biologie de l’allergie. Discussion Ces recommandations n’ont pas vocation à décrire l’ensemble des outils pour le diagnostic ou le suivi des maladies allergiques, mais concernent des points d’amélioration de la prise en charge de l’allergie, identifiés à l’aide de recommandations consensuelles nationales et internationales ou d’études de pratiques publiées depuis 2005. En l’absence de telles données, l’avis et l’expérience du groupe de travail a été exprimé. Conclusion Ces recommandations de bonne pratique de prescription et d’interprétation des examens biologiques pour le diagnostic et le suivi des hypersensibilités allergiques selon la méthode RPC de la HAS, apportent en 2018 une actualisation rendue nécessaire par l’évolution des concepts et des outils.

Les dosages d’IgG anti-aliments : méthodes et pertinence clinique des résultats. Position du groupe de travail de biologie de la Société française d’allergologie

Article

Apr 2018

There is an increasing tendency in western countries to attribute to food intolerance various clinical types of gastrointestinal disorders, joint pain or rheumatoid arthritis (RA), migraine and chronic fatigue. Several authors have reported a greater frequency of positive anti-food IgG in patients presenting irritable bowel syndrome (IBS), chronic inflammatory bowel disease (IBD) and RA compared to healthy controls. Over the last decade, screening tests have become routinely available on prescription but are also freely available over the Internet. These assays are used to create diets that avoid IgG-positive foods in the hope of improving symptoms thought to be related to the consumption of these foods associated with IgG-mediated intolerance reactions. The purpose of this study is to review the mechanisms involved in food intolerance and the physiological and pathological role of IgG immune response. Commercially available assays for food IgG are reviewed. Studies based on anti-food IgG determination applied to various diseases are reviewed and discussed. Considerable controversy surrounds the clinical relevance of anti-food IgG assays because of their poor positive predictive value. The recommendations made on the basis of these assays are likely to jeopardize the health of patients by delaying correct diagnosis or encouraging them to follow a mostly useless and occasionally harmful diet. The frequently high direct and indirect costs of assays and avoidance diets may be avoided in favor of other diagnostic strategies. Finally, in the current state of medical knowledge, anti-food IgG tests should not be performed routinely to establish a food intolerance diagnosis or to devise an avoidance diet. They should be used solely for research purposes.

Consommation de gluten et syndrome de l'intestin irritable : revue de la littérature et intérêt pour le médecin généraliste

Thesis

May 2013

Akpemado Benoït

Le syndrome de l'intestin irritable (SII) est un trouble digestif fonctionnel trèsfréquemment rencontré en médecine générale. Depuis quelques années, certains patients atteints de troubles digestifs fonctionnels ont expérimenté un amendement de leurs symptômes en excluant le gluten de leur alimentation. Dénommé sensibilité au gluten (SG), cette nouvelle entité parmi les troubles liés au gluten est définie par des réactions cliniques (digestives ou extradigestives) qui apparaissent à l'ingestion de gluten, et disparaissent à son exclusion, alors que la maladie coeliaque et l'allergie au blé ont été éliminées. Ce concept étant récent et pouvant remettre en cause la prise en charge du syndrome de l'intestin irritable, nous avons réalisé une revue de la littérature pour tester l'hypothèse selon laquelle l'ingestion de gluten peut être responsable d'un syndrome de l'intestinirritable.Les données de la littérature sont encore trop peu nombreuses. La méthodologie decertaines études est souvent critiquable, mais la plupart a analysé l?impact du gluten surl'histologie duodénale. Seules trois études à ce jour, dont 2 études randomisées ontutilisé la référence diagnostique des troubles liés au gluten, non allergiques et noncoeliaques : un régime sans gluten suivi d?une réintroduction du gluten en doubleaveugle contrôlée placebo. Cela permet effectivement de confirmer l'existence d'unesensibilité au gluten non coeliaque.2 observations cliniques de médecine générale, présentées en complément du travailbibliographique, indiquent une efficacité du régime sans gluten sur le score de qualitéde vie IBS-QOL.La découverte de cette nouvelle entité devrait avoir un impact concret dans la pratiquequotidienne du médecin généraliste lors de la prise en charge d'un SII. Outre le fait dediminuer la prescription de certains examens complémentaires inutiles et couteux, celapermettrait pour un sous groupe non négligeable de patients atteints de SII de découvrirune réponse tangible et durable à leurs problèmes digestifs chroniques

Management of celiac disease: From evidence to clinical practice

Article

Full-text available

Nov 2017

Celiac disease (CD) is a complex polygenic disorder, which involves genetic factors human leukocyte complex (HLA) and non-HLA genes, environmental factors, innate and adoptive immunity, and a robust chronic T-mediated autoimmune component. The main goal of the present monograph is to define a methodological approach for the disease, characterized by frequent late diagnosis, in order for the physician to become aware of the disease management, the diversity of the clinical presentation itself and in different patients. A unique attention is payed to the specific diagnostic tests to define a correct and accurate application of them, and in addition, to disease follow-up and possible complications. Moreover, a dedicated space is assigned to refractory CD, to potential CD and non-celiac gluten sensitivity. Legislative aspects of the celiac disease in Italy are addressed, too. The celiac disease guidelines and their evaluation by means of Appraisal of Guidelines, Research and Evaluation II instrument allow us to classify the different recommendations and to apply them according to the stakeholders’ involvement, pertinence, methodological accuracy, clarity and publishing independence. Finally, the most current scientific evidence is taken into account to create a complete updated monograph.

HLA-DQ2 and -DQ8 haplotypes frequency and diagnostic utility in celiac disease patients of Gaza strip, Palestine

Article

Full-text available

Nov 2017

Purpose: Celiac disease (CD) diagnosis can be established by serological and small bowel biopsy (SBB), while absence of HLA-DQ2 and -DQ8 haplotypes excludes the disease. The present study aims at evaluating the diagnosis of a representative sample of pediatric and adult CD patients of Gaza strip in light of DQ2 and DQ8 haplotypes expression. Methods: Unrelated CD patients (n = 101) and matched healthy controls (n = 97) were genotyped for DQA1*05, DQB1*02 and DQB1*03:02 alleles by allele-specific real-time PCR. The diagnosis was re-evaluated according to the patient laboratory tests and HLA-DQ genotype. Results: The diagnosis of 35 patients who have been managed for CD could not be confirmed. Twenty-five of them were diagnosed upon their clinical presentation only. The remaining were either negative for serological and SBB tests or negative for HLA-DQ haplotypes. The HLA-DQ alleles were negative in 4 SBB and one Anti-EMA positive patients. The frequency of DQ2 and DQ8 haplotypes among the remaining 65 confirmed cases was 70.8 and 15.4%, respectively, compared to 17.5 and 27.8% in the controls. The DQB1*02 allele was the most common in the cases (84.6%) followed by DQA1*05 allele (80%) and DQB1*03:02 allele (20%). The DQA1*05 allele was commonest in the control group (54.6%) followed by DQB1*02 allele (42.3%) and DQB1*03:02 allele (28.9%). Conclusions: Absence of HLA-DQ2 and HLA-DQ8 genotyping in the workup of patients may result in CD misdiagnosis, particularly in a setting with poor histopathological diagnostic capacity.

JAAPA 2015 gaesser angadi

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Nov 2017

Identification of metalloproteases like domain in Triticum aestivum α/β gliadin protein from bioinformatics perspective: A Hypothesis

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In the last decade, the ingestion of gluten, a heterogeneous complex of proteins present in wheat, rice, barley and probably in oats, has been associated with clinical disorders, such as celiac disease, wheat allergy and recently to non-celiac gluten sensitivity or wheat intolerance syndrome. Gluten-related disorders, which are becoming epidemiologically relevant with an estimated global prevalence of about 5%, require the exclusion of gluten from the diet. For the past 5 years, an important shift in the availability of gluten-free products, together with increased consumption in the general population, has been recorded and is estimated to be about 12–25%. Many people follow a self-prescribed gluten-free diet, despite the fact that the majority have not first been previously excluded, or confirmed, as having gluten disorders. They rely on claims that a gluten-free diet improves general health. In this review, we provide an overview of the clinical disorders related to gluten or wheat ingestion, pointing out the current certainties, open questions, possible answers and several doubts in the management of these conditions. • KEY MESSAGE • Incidence of gluten-related disorders is increased in the last decade and self-diagnosis is frequent with inappropriate starting of a gluten-free diet. • Gluten and wheat are considered as the most important triggers to coeliac disease, wheat allergy and non-celiac gluten sensitivity. • Pediatricians, allergologist and gastroenterologist are involved in the management of these conditions and appropriate diagnostic protocols are required.

Symptomatic efficacy of buckwheat products in non-celiac gluten sensitivity: a randomized dietary intervention trial

Article

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Jun 2017
ASIA PAC J CLIN NUTR

Background and objectives: Buckwheat (Fagopyrum esculentum) is a gluten-free grain with acclaimed benefi-cial effects on human health. Our aim was to assess the effect of buckwheat products on intestinal/extra-intestinal symptoms and biochemical parameters in patients with Non-Celiac Gluten Sensitivity (NCGS). Methods and study design: A randomized, crossover trial with two intervention phases was conducted on 19 NCGS patients over a 12 week-period. The participants were assigned to consume products made from buckwheat or to maintain their normal gluten-free diet for 6 weeks in a random order. Symptoms due to NCGS were evaluated using two questionnaires. Results: During the intervention period with buckwheat products, patients experienced a signifi-cant decrease in the severity of abdominal pain and bloating (p=0.03). In contrast, the control group showed a significant worsening trend for the majority of NCGS symptoms such as nausea, headache, joint/muscle pain, and attention disorders. The replacement diet with buckwheat products also resulted in a significant increase of serum magnesium (+4.7%) and a significant reduction in the circulating levels of some pro-inflammatory cytokines such as interferon gamma (-33.3%) and monocyte chemotactic protein-1 (-46.5%). Conclusion: The study supports the positive effects of buckwheat for NCGS patients, showing that this alternative cereal can contribute to the re-duction of both negative gastro-intestinal and related symptoms, and nutritional deficiencies, and lead to an im-provement in inflammatory profile.

Screening for coeliac disease in adult patients with type 1 diabetes mellitus: Myths, facts and controversy

Article

Full-text available

Jul 2016

This review aims at summarizing the present knowledge on the clinical consequences of concomitant coeliac disease (CD) in adult patients with type 1 diabetes mellitus (T1DM). The cause of the increased prevalence of CD in T1DM patients is a combination of genetic and environmental factors. Current screening guidelines for CD in adult T1DM patients are not uniform. Based on the current evidence of effects of CD on bone mineral density, diabetic complications, quality of life, morbidity and mortality in patients with T1DM, we advise periodic screening for CD in adult T1DM patients to prevent delay in CD diagnosis and subsequent CD and/or T1DM related complications.

Elevated Immune Response to Gliadin in Autism: Association with Gastrointestinal Symptoms but Not Celiac Disease

Conference Paper

Jan 2012

Prevalence of dental findings of children with celiac disease in Libya: a comparative study

Article

Oct 2014

Background and objectives: Celiac disease is a disease affecting the digestive system whereby the patient is unable to tolerate gluten-containing food. The aims of this study were to study the prevalence of dental defects and oral hygiene status of a group of celiac disease patients in Benghazi. Materials and methods: A group of celiac disease patients (n = 40 & Male: Female ratio is 1: 2.4 & age range 3-19 years, mean 10 years, SD ± 4.8) were recruited from Benghazi Pediatric Hospital where they had already been diagnosed in gastroenterology units at private clinics. The patient’s dental status was assessed through measuring their Decayed, Missing and Filled Teeth index (DMFT), oral hygiene index (OHI) and CPITN using disposable mouth mirrors, explorers and periodontal probes. Descriptive statistics was applied to give a picture about the oral hard and soft tissue prevalence this group of patients. Results: Descriptive statistics of the celiac sample showed that 29 (72.5%) had enamel hypoplastic defects. The mean and SD values for DMFT, CPITN and OHI were measured (DMFT: 4.5 SD ± 4.7 & CPITN: 0.8 SD ± 0.5; and OHI: 1.1 SD ± 0.7). Besides, only two patients (6.4%) reported a history of oral ulceration during the course of their therapy. Healthy controls showed comparative values, being less in only OHI, while they were slightly more in DMFT and CPITN. Conclusion: This is a cross-sectional clinical survey showing that patients with celiac disorder should be expected to have higher prevalence of defective incisor teeth, which makes their front teeth liable to traumatic fracture. The presence of frequent soft tissue ulcers in their mouths might indicate a warning sign of the possibility to develop the disease and thus urge the child’s parents or guardians to consult a physician to confirm or negate the suspicion.

Neurological disorders and Celiac disease

Article

Full-text available

Dec 2015

Celiac disease (CD) determines neurologic manifestations in 10% of all CD patients. We describe the most common clinical manifestations as cerebellar ataxia, gluten encephalopathy, multiple sclerosis, peripheral neuropathies, sensorineural hearing loss, epilepsy, headache, depression, cognitive deficiencies and other less described clinical conditions. Our aim is to perform, as more as possible, a review about the most recent update on the topics in international literature. It is important to consider clinical neurological manifestations in celiac patients and to research these conditions also in the follow-up because they may start also one year after the start of gluten free diet (GFD) as peripheral neuropathy. The association with autism is analysed and possible new association with non-celiac gluten sensitivity (NCGS) are considered.

The brain-gut axis dysfunctions and hypersensitivity to food antigens in the etiopathogenesis of schizophrenia

Article

Full-text available

Jan 2015

Despite over 100-year history of research on schizophrenia, its etiology is still not fully understood, which might be due to the significant heterogeneity in terms of both its course, as well as the etiopathogenesis. One of the best-proven mediating mechanisms in the development of schizophrenia is the immuno-inflammatory response, the sources of which are believed to be the dysfunctions of brain-gut axis and pathological processes occurring in the intestines. This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow's milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups. However, further research is needed on links between the intestinal microbiome and intestinal function as factors mediating the activation of the immune system and the development and further course of schizophrenia.

The brain-gut axis dysfunctions and hypersensitivity to food antigens in the etiopathogenesis of schizophrenia

Article

Full-text available

Jan 2015

Hanna Karakula-Juchnowicz

Despite over 100-year history of research on schizophrenia, its etiology is still not fully understood, which might be due to the significant heterogeneity in terms of both its course, as well as the etiopathogenesis. One of the best-proven mediating mechanisms in the development of schizophrenia is the immuno-inflammatory response, the sources of which are believed to be the dysfunctions of brain-gut axis and pathological processes occurring in the intestines. This paper is a review of the literature on this subject which presents factors both involved in the functioning of brain-gut axis and important for the development of schizophrenia, i.e. 1. intestinal microbiome (intestinal microbiota), 2. permeable intestine (leaky gut syndrome), 3. hypersensitivity to food antigens, including gluten and casein of cow’s milk. Research results seem to be very promising and indicate the possibility of improved clinical outcomes in some patients with schizophrenia by modifying diet, use of probiotics, and the implementation of antibiotic therapy of specific treatment groups. However, further research is needed on links between the intestinal microbiome and intestinal function as factors mediating the activation of the immune system and the development and further course of schizophrenia.

Navigating the gluten-free boom

Article

Full-text available

Aug 2015

Gluten-free diets have gained popularity with the public at a rate greater than would be expected based on the prevalence of gluten-related disorders such celiac disease, nonceliac gluten sensitivity, and wheat allergy. This article reviews gluten-related disorders, indications for gluten-free diets, and the possible health benefits of gluten. Despite the health claims for gluten-free eating, no published experimental evidence supports weight-loss with a gluten-free diet or suggests that the general population would benefit from avoiding gluten.

Coeliac disease and gluten-related disorders in childhood

Article

Jun 2015
NAT REV GASTRO HEPAT

Gluten-related disorders such as coeliac disease, wheat allergy and noncoeliac gluten sensitivity are increasingly being diagnosed in children. Coeliac disease occurs frequently, affecting 1-3% of the Western population. The condition manifests at a very young age, more so in girls, and is related to the HLA genotype. Coeliac disease might be considered a public health problem and, as primary prevention is not possible, the debate on mass screening should be reopened. Wheat proteins, including gluten, are responsible for one of the most common food allergies in children: wheat allergy. Unlike coeliac disease and wheat allergy, noncoeliac gluten sensitivity is an unclear and controversial entity. These three gluten-related disorders are treated with a gluten-free diet. In coeliac disease, the diet should be strictly followed, whereas wheat allergy only requires wheat elimination and in noncoeliac gluten sensitivity occasional trials of gluten reintroduction can be done. A good diagnostic work-up is important for gluten-related disorders in childhood to avoid unnecessary restrictive diets in children. In this Review, we provide an overview of the pathogenesis, diagnosis and management of the most common gluten-related disorders in children.

Ikke-cøliakisk glutensensitivitet: - en av de glutenrelaterte lidelsene?

Article

Mar 2014

Lise Friis Pedersen

Zöliakie/Einheimische Sprue

Chapter

Jul 2015

Zöliakie/Einheimische Sprue

Chapter

Feb 2016

Molecular triggers of non-celiac wheat sensitivity

Chapter

Jan 2021

Armin Alaedini

Non-celiac gluten/wheat sensitivity (NCWS) is characterized by a range of intestinal and extraintestinal symptoms in response to ingestion of wheat and related cereals in individuals in whom celiac disease and wheat allergy are ruled out. Recent data support the existence of a biological basis for NCWS, as demonstrated by several dietary intervention trials and the discovery of biomarkers of immune activation and compromised intestinal barrier in patients. Despite the fact that the condition is more commonly known as a gluten sensitivity, the identity of the molecular component(s) of wheat responsible for triggering the associated symptoms remains a subject of debate and research. Gluten proteins, amylase/protease inhibitor proteins, and fermentable carbohydrates are among the various possible culprits proposed based on preclinical or clinical data. This review is aimed at examining the evidence, including the strength of the available data and their potential relevance to the pathogenic mechanism and clinical presentation of NCWS.

Non-celiac wheat sensitivity: rationality and irrationality of a gluten-free diet in individuals affected with non-celiac disease: a review

Article

Full-text available

Jan 2021
BMC GASTROENTEROL

Non-celiac gluten or wheat sensitivity (NCWS) is a “clinical entity induced by the ingestion of wheat leading to intestinal and/or extraintestinal symptoms that improve once the wheat-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded”. This mostly accepted definition raises several points that remain controversial on this condition. In the present review, the authors summarize the most recent advances in the clinic and research on NCWS through an accurate analysis of different studies. We screened PubMed, Medline, Embase, and Scopus using the keywords “non-celiac gluten sensitivity”, “non-celiac wheat sensitivity”, and “diagnosis”. We would like to emphasize two main points, including (A) the controversial clinical and etiological aspects in different trials and experiences with particular attention to the Salerno criteria for the diagnosis of NCWS and (B) the histological aspects. The etiology of NCWS remains controversial, and the relationship with irritable bowel syndrome is obscure. Histologically, the duodenal mucosa may show a variable pattern from unremarkable to a slight increase in the number of T lymphocytes in the superficial epithelium of villi. The endorsement of this disease is based on a positive response to a gluten-free diet for a limited period, followed by the reappearance of symptoms after gluten challenge. The Salerno expert criteria may help to diagnose NCWS accurately. Social media and inaccurate interpretation of websites may jeopardize the diagnostic process if individuals self-label as gluten intolerant.

Immunopathogenesis of Celiac Disease

Chapter

Nov 2014

Celiac Disease Symptoms in Athletes: Prevalence Indicators of Perceived Quality of Life

Article

Apr 2020

Background Celiac disease (CD) is a common gastrointestinal pathology; however, prevalence and comorbidities are unknown in collegiate athletics. Hypotheses (1) Athletes will have similar odds of CD as general population estimates (approximately 1 in 141) based on self-report and signs and symptoms, (2) athletes scoring higher on the Celiac Symptom Index (CSI) will have lower self-reported quality of life (QoL), (3) athletes scoring higher on the CSI will have higher depression scores, and (4) athletes scoring higher on the CSI will have higher perceived stress scores. Study Design Epidemiological cross-sectional study. Level of Evidence Level 4. Methods The CSI, WHO Quality of Life-BREF, Beck Depression Inventory, and Perceived Stress Scale were used to assess patients’ signs and symptoms of CD and psychosocial measures/QoL in male and female National Collegiate Athletic Association (all divisions) athletes (N = 141). Participants also self-reported a formal diagnosis of CD. Chi-square analyses determined CD prevalence. Odds ratios determined risk for either being diagnosed with CD or reporting more symptoms than the general population. Correlational analyses determined whether symptoms correlated with QoL and psychosocial measures. Results Athletes were 3.85 times (95% CI, 0.42-34.89) more likely to report a CD diagnosis and were 18.36 times (95% CI, 2.40-140.48) more likely to report a high degree of CD symptoms than the general population. Athletes with more symptoms had worse physical, psychological, social, and environmental QoL indicators and higher depression and perceived stress scores. Conclusion Athletes may be a higher risk population for experiencing CD and report greater signs/symptoms compared with general population estimates. Additionally, athletes with higher CD symptom scores also reported poorer QoL. Clinical Relevance Allied health care professionals should be aware of the diversity of CD symptoms and be prepared to refer athletes when gastrointestinal symptoms persist to ensure proper care and unhampered performance.

Maladies liées au gluten

Article

Full-text available

Mar 2020

Non-Celiac Gluten Sensitivity in patients with severe abdominal pain and bloating: The accuracy of ALCAT 5

Article

Sep 2018

Background and aims: Non-Celiac Gluten Sensitivity (NCGS) is a recently proposed clinical condition causing both intestinal and extra-intestinal symptoms, without gastrointestinal lesions, which improve on avoiding gluten intake, in the absence of celiac disease and wheat allergy. The prevalence of this condition is still a matter of debate, in part due to the very recent introduction of an accepted diagnostic test, a double-blind, placebo controlled gluten challenge. However, this is a lengthy and cumbersome procedure, theoretically burdened by a significant reduction of patient compliance. ALCAT 5 is an automated in vitro test evaluating the toxic effect of gluten on neutrophils by the exposure of these cells to a gluten-containing extract of gluten-containing cereals. The test is very simple to perform, the results are rapidly obtained, and might represent, if sufficiently accurate, a promising alternative to diagnose gluten intolerance. The aim of this study was the comparison of ALCAT 5 results with those of a double-blind, placebo-controlled, gluten challenge, in a group of patients with clinically-suspected NCGS. Methods: Twenty-five patients (M/F 3/22, mean age 32 ± 4 yrs) with severe functional abdominal pain and bloating, who had previously undergone the ALCAT 5 test, were enrolled. All the subjects reported their symptoms on a gluten-containing diet and considered gluten the causal agent. Following the Salerno Experts' Criteria, they underwent a double-blind, placebo controlled trial with gluten vs placebo. A mean value during gluten ingestion >30% of the value during placebo was considered as indicative of gluten sensitivity. Results: After blinded administration of gluten, 13 out of 25 (52%) patients showed an increase in the severity of abdominal pain, and 11 out of 25 (44%) showed an increase in the severity of abdominal bloating. Considering these two symptoms together, in 16 patients out of 25 (64%), blinded gluten administration induced an increase of abdominal pain and/or bloating. The ALCAT 5 test proved to be positive in 20 and negative in 5 patients. In sixteen patients out of 25 the result of ALCAT 5 agreed with the double-blind trial (64%). In particular, both tests were positive in 14 patients and negative in 2. Conclusions: In this subgroup of patients, ALCAT 5 could be used to support the clinical suspicion of the presence of NCGS and to address these patients to a blinded gluten challenge.

Pathogenesis, diagnosis and treatment of anaemia in immune-mediated gastrointestinal disorders

Article

May 2018

Immune‐mediated disorders affecting the gastrointestinal (GI) tract may compromise GI integrity, interfere with the absorption of nutrients and cause bleeding and inflammation. All these features contribute to the pathogenesis of anaemia, the most prevalent extra‐intestinal manifestation of immune‐mediated GI disorders. Anaemia is most commonly due to iron deficiency and/or inflammation, but vitamin deficiencies and, more infrequently, autoimmune haemolysis or drug‐induced myelosuppression can be involved. Here we address several issues related to the differential diagnosis and treatment of anaemia in immune‐mediated GI disorders, giving particular relevance to the problem of iron deficiency anaemia associated with inflammation. It is emphasized how, in most cases, anaemias due to iron or vitamin deficiencies are best treated by parenteral administration of the deficient factor(s), and how the available high dose intravenous (IV) iron formulations can reduce ambulatory and social costs of IV iron supplementation, while improving patient's compliance to treatment. Actual and future treatment possibilities for anaemia of inflammation, involving the use of erythropoiesis stimulating agents, biologicals and hepcidin inhibitors are discussed.

Delay in Diagnosis of Celiac Disease in Patients Without Gastrointestinal Complaints

Article

Jun 2017

Purpose The purpose of our study is to investigate the delay in diagnosis of patients with biopsy-proven celiac disease in those who present with gastrointestinal complaints vs non-gastrointestinal complaints at our tertiary care center. Celiac disease is an autoimmune disorder which affects approximately 1% of the population worldwide. Celiac disease can have variable clinical presentations characterized by either predominately gastrointestinal symptoms or may present without any gastrointestinal symptom. Methods We retrospectively reviewed 687 adult patients’ charts who carried the diagnosis of celiac disease. Patients included had biopsy-proven celiac disease and were categorized based on presence or absence of gastrointestinal symptoms prior to their diagnosis. Results 101 patients with biopsy-proven celiac disease met inclusion criteria. 52 patients presented with gastrointestinal symptoms and 49 had non-gastrointestinal complaints. Results from Mann-Whitney statistical analysis showed a median delay in diagnosis of 2.3 months for gastrointestinal symptoms group and 42 months for non-gastrointestinal group ( P<0.001). 43.2% patients with non-gastrointestinal symptoms had abnormal thyroid-stimulating hormone (TSH) as opposed to 15.5% in the gastrointestinal symptom group (P=0.004). Of patients with non-gastrointestinal symptoms, 69.4% had anemia compared to 11.5% of gastrointestinal symptom group (P<0.001). The majority of patients in the non-gastrointestinal symptom group 68% were noted to have abnormal bone density scans compared to 41% in the gastrointestinal symptom group. No gender differences were noted on Chi square analysis between the two groups (p=0.997). Conclusions Although there is growing awareness of celiac disease, the delay in diagnosis for patients without gastrointestinal symptoms remains prolonged, with an average delay of 3.5 years.

The Linkage Between Fitness, Nutrition and Mind for our Well-being, Abundance and Health

Article

Full-text available

May 2014

Anat Bloch Feldman

Wheat challenge in self-reported gluten sensitivity: a comparison of scoring methods

Article

Oct 2016
SCAND J GASTROENTERO

Background: The condition non-coeliac gluten sensitivity (NCGS) is clinically similar to coeliac disease, but lack objective diagnostic criteria. Symptom relief on gluten-free diet followed by gluten containing food challenge may confirm the condition in clinical settings. Aim: To describe the results of an open bread challenge in patients with suspected NCGS, and to compare the results with recently suggested cut-offs for symptom change. Material and methods: Fifty-six patients (12 males) self-instituted on gluten-free diet with negative coeliac disease diagnostics were examined for NCGS by an open bread challenge. Symptoms were reported by Gastrointestinal Symptom Rating Scale, IBS-version (GSRS-IBS) and visual analogue scale (VAS). Results were retrospectively compared to the Salerno and Monash cut-offs for symptom change. Results: Forty-seven patients were diagnosed with NCGS. Total GSRS-IBS score and overall symptoms by VAS increased significantly in NCGS (p < .001), but not in non-NCGS patients (p < .12 and p = .08, respectively). Total GSRS-IBS challenge score and overall symptoms by VAS were significantly higher in NCGS than in non-NCGS patients (53 vs. 37, p = .004 and 76 vs. 39 mm, p = .02, respectively). Applying the Salerno and Monash cut-offs, 63 and 75% would be classified with NCGS, respectively. According to total GSRS–IBS absolute agreement was lowest between clinician’s diagnosis and Salerno cut-off (63%) and highest between Salerno and Monash cut-offs (88%). Conclusion: Clinician diagnosed 85% with NCGS. The proportion of NCGS was lower according to the Salerno and Monash cut-offs. The Salerno cut-off should be the starting point for a common definition of symptom change.

For gluten or wheat sensitivity

Article

Nov 2014
ALLERGOLOGIE

Ute Körner

Diet adherence and gluten exposure in coeliac disease and self-reported non-coeliac gluten sensitivity

Article

Dec 2015

Background/objectives: Adherence to gluten-free diet in self reported non-coeliac gluten sensitive subjects is scarcely researched. Objectives of the study were to compare dietary adherence in coeliac disease (CD) subjects and in non-coeliac gluten sensitive (NCGS) subjects, and to estimate gluten exposure based on weighed food records and analysis of gluten content in selected food items. Subjects/methods: Twenty-three subjects with biopsy verified CD on a gluten-free diet and 34 HLA-DQ2(+) NCGS subjects on a self-instituted gluten-free diet were enrolled. The latter group was under investigation of CD. Dietary adherence was assessed by frequency questionnaire and structured forms supplied by weighed food records. For the analyses of food samples, the sandwich R5-ELISA, Ridascreen(®) Gliadin competitive method was used. Results: There was no difference in dietary adherence between CD and NCGS subjects (83% vs 68%, p = 0.21). NCGS subjects were mainly self-educated in gluten-free diet compared to CD subjects (91% and 39%, respectively, p < 0.001). In non-adherent subjects, there was no difference in gluten exposure between CD and NCGS (10 vs 138 mg/day, p = 0.83). There was no difference in BMR-factor between CD and NCGS subjects, or between adherent and non-adherent subjects. Conclusions: Both CD and NCGS subjects were largely adherent, and adherence did not differ between the groups. Gluten exposure varied greatly, and some CD and NCGS subjects reached gluten intake above 500 mg/day, which might have considerable health effects on the individual, especially in case of coeliac disease.

Definition of Celiac Disease and Gluten Sensitivity

Chapter

Jan 2014

As an important component of wheat, rye, and barley, gluten can be found in a large variety of foods consumed throughout the world (breads, pasta, pizza, etc.). However, the introduction of gluten-containing grains in the human diet about 10,000 years ago created the conditions for human diseases related to gluten exposure. These reactions to gluten represent a heterogeneous set of conditions, including celiac disease, non-celiac gluten sensitivity, and wheat allergy, which combined affect about 10 % of the general population. These three conditions represent distinct pathophysiological reactions to gluten ingestion, with differing clinical presentations, serological markers, and long-term treatments. Though current research strives to clarify the boundaries between these entities, their differences can be difficult to distinguish. This chapter provides an overview of the ever-evolving definitions of gluten-related disorders.

Absence of somatization in non-coeliac gluten sensitivity

Article

Full-text available

Apr 2012
SCAND J GASTROENTERO

In contrast to coeliac disease (CD), the mechanism behind non-coeliac gluten sensitivity (NCGS) is unclear. The aims of the study were to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals compared with CD patients and healthy controls, and to compare the response to gluten challenge between NCGS and CD patients. We examined 22 CD patients and 31 HLA-DQ2+ NCGS patients without CD, all on a gluten-free diet. All but five CD patients were challenged orally for 3 days with gluten; symptom registration was performed during challenge. A comparison group of 40 healthy controls was included. Patients and healthy controls completed questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life. The NCGS patients reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after gluten challenge than CD patients. There were no significant differences between CD and NCGS patients regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. The somatization level was low in CD and NCGS groups. Symptom increase after gluten challenge was not related to personality in NCGS patients. NCGS patients did not exhibit a tendency for general somatization. Personality and quality of life did not differ between NCGS and CD patients, and were mostly at the same level as in healthy controls. NCGS patients reported more symptoms than CD patients after gluten challenge.

Corrigendum: Assessing Possible Celiac Disease by an HLA-DQ2-Gliadin Tetramer Test

Article

Full-text available

Apr 2012
AM J GASTROENTEROL

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)

The Oslo definitions for coeliac disease and related terms

Article

Full-text available

Feb 2012
GUT

Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.

Early tissue transglutaminase-mediated response underlies K562(S)-cell gliadin dependent agglunation

Article

Full-text available

Feb 2012
Pediatr Res

INTODUCTION: K562(S) agglutination has been used as a rapid and economic tool for the in vitro screening of the toxicity of cereal fractions and prolamins in celiac disease (CD). A strict correlation has been reported between the toxicity of cereals and cereal fractions for celiac patients and their ability to agglutinate K562(S) cells. Whether this specificity of K562(S)-cell agglutination is caused by the activation of the same pathogenic events triggered by toxic cereal fractions in CD intestine or simply represents a bystander event of gluten toxicity is, however, unknown. K562(S) cells were incubated in vitro with the peptic-tryptic digest of wheat gliadin. The agglutination of K562(S) cells by wheat gliadin peptides is orchestrated by a cascade of very early events occurring at the K562(S)-cell surface similar to those occurring at the intestinal epithelial surface. They involve a rapid increase in intracellular calcium levels that activate tissue transglutaminase (TG2), leading to a rapid actin reorganization that is pivotal in driving cell agglutination. These specific effects of toxic cereals are phenocopied by the gliadin-derived peptide p31-43, which orchestrates the activation of innate response to gliadin in CD. Our study provides the rationale for the extensive use of K562(S)-cell agglutination as a valuable tool for screening cereal toxicity.

Autism spectrum disorder and celiac disease: No evidence for a link

Article

Full-text available

Jan 2012
ARQ NEURO-PSIQUIAT

To evaluate the possible association between celiac disease (CD) and/or gluten sensitivity (GS) and autism spectrum disorder (ASD). Occurrences of CD were determined in a group of children and adolescents affected by ASD and, conversely, occurrences of ASD were assessed in a group of biopsy-proven celiac patients. To detect the possible existence of GS, the levels of antigliadin antibodies in ASD patients were assessed and compared with the levels in a group of non-celiac children. The prevalence of CD or GS in ASD patients was not greater than in groups originating from the same geographical area. Similarly the prevalence of ASD was not greater than in a group of biopsy-proven CD patients. No statistically demonstrable association was found between CD or GS and ASD. Consequently, routine screening for CD or GS in all patients with ASD is, at this moment, neither justified nor cost-effective.

Important Lessons Derived From Animal Models of Celiac Disease

Article

Full-text available

Aug 2011
INT REV IMMUNOL

Several animal models have been recently developed to recapitulate various components of the complex process that is celiac disease. In addition to the increasing diversity of murine models there are now monkey models of celiac disease. Mouse strains and protocols have been developed that are now just beginning to address the complex interactions among the innate and adaptive immune responses to gluten, as well as gluten-dependent autoimmunity in celiac disease. The most important conclusion that these models have provided us with so far is that while all three components (innate gluten sensitivity, adaptive gluten sensitivity, and autoimmunity) are independent phenomena, all are necessary for celiac disease to develop.

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: Celiac disease and gluten sensitivity

Article

Full-text available

Mar 2011
BMC MED

Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders. CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity. Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293). This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.

Assessing Possible Celiac Disease by an HLA-DQ2-gliadin Tetramer Test

Article

Full-text available

Mar 2011
AM J GASTROENTEROL

Investigation of uncertain celiac disease (CD) in patients already on a gluten-free diet (GFD) is difficult. We evaluated HLA-DQ2-gliadin tetramers for detection of gluten-specific T cells in peripheral blood and histological changes in the duodenum after a short gluten challenge as a diagnostic tool. HLA-DQ2+ individuals on a GFD for at least 4 weeks were investigated; 35 with uncertain diagnosis, 13 CD patients, and 2 disease controls. All participants had a challenge with four slices of gluten-containing white bread, daily for 3 days (d1-d3). An esophagogastroduodenoscopy with biopsy sampling was done on d0 and d4. Biopsies were scored according to revised Marsh criteria. Peripheral blood CD4+ T cells were isolated, stained with HLA-DQ2-gliadin peptide tetramers, and analyzed by flow cytometry on d0 and d6. After challenge, a positive tetramer test was seen in 11/13 CD patients. Four of these subjects also showed typical histological changes on challenge. Of the 35 patients with uncertain diagnosis, 3 were diagnosed with CD. Two of these three patients had both positive tetramer staining and histological changes in biopsies after challenge. Tetramer staining for gluten-specific T cells is a sensitive method in detecting an immune response in CD patients after a short gluten challenge. The prevalence of CD in the group with self-prescribed GFD was about 10%.

Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial

Article

Full-text available

Jan 2011
AM J GASTROENTEROL

Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

The Impact of Misdiagnosing Celiac Disease at a Referral Centre

Article

Full-text available

Sep 2009
CAN J GASTROENTEROL

In the past few years, the number of celiac disease diagnoses not confirmed at the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, a tertiary referral centre, was particularly high. Therefore, a decision was made to investigate the reasons why these diagnoses were wrong and by whom they had been made. The clinical histories of all celiac patients referred to the centre were re-evaluated. Between December 1998 and January 2007, 614 patients who were diagnosed at other institutions and presumed to be affected by celiac disease attended the tertiary referral outpatient clinic. The histological and serological results allowed for confirmation the diagnosis in 434 patients. In the remaining 180 patients, the initial diagnosis of celiac disease could not be confirmed; therefore, the patients were re-investigated. After re-evaluation, the diagnosis of celiac disease was confirmed in only 61 of these 180 cases. The reasons for incorrect initial diagnosis were analyzed. A mere 80% correct diagnosis rate is a very disappointing result. Although it should be obvious that celiac disease must be investigated with duodenal biopsies and celiac antibody testing, this well-known strategy is not always followed, probably resulting in an incorrect diagnosis.

Prevalence of Celiac Disease and Gluten Sensitivity in the United States Clinical Antipsychotic Trials of Intervention Effectiveness Study Population

Article

Full-text available

Jun 2009

Celiac disease (CD) and schizophrenia have approximately the same prevalence, but epidemiologic data show higher prevalence of CD among schizophrenia patients. The reason for this higher co-occurrence is not known, but the clinical knowledge about the presence of immunologic markers for CD or gluten intolerance in schizophrenia patients may have implications for treatment. Our goal was to evaluate antibody prevalence to gliadin (AGA), transglutaminase (tTG), and endomysium (EMA) in a group of individuals with schizophrenia and a comparison group. AGA, tTG, and EMA antibodies were assayed in 1401 schizophrenia patients who were part of the Clinical Antipsychotic Trials of Intervention Effectiveness study and 900 controls. Psychopathology in schizophrenia patients was assessed using the Positive and Negative Symptoms Scale (PANSS). Logistic regression was used to assess the difference in the frequency of AGA, immunoglobulin A (IgA), and tTG antibodies, adjusting for age, sex, and race. Linear regression was used to predict PANSS scores from AGA and tTG antibodies adjusting for age, gender, and race. Among schizophrenia patients, 23.1% had moderate to high levels of IgA-AGA compared with 3.1% of the comparison group (χ(2) = 1885, df = 2, P < .001.) Moderate to high levels of tTG antibodies were present in 5.4% of schizophrenia patients vs 0.80% of the comparison group (χ(2) = 392.0, df = 2, P < .001). Adjustments for sex, age, and race had trivial effects on the differences. Regression analyses failed to predict PANSS scores from AGA and tTG antibodies. Persons with schizophrenia have higher than expected titers of antibodies related to CD and gluten sensitivity.

Diagnosis and treatment of celiac disease

Article

Full-text available

Feb 2009
MUCOSAL IMMUNOL

The understanding of the pathogenesis of celiac disease has made huge advances in recent years. The disease is caused by an inappropriate immune response to dietary gluten proteins. This immune response is controlled by CD4(+) T cells in the lamina propria that recognize gluten peptides in the context of disease predisposing HLA-DQ2 and HLA-DQ8 molecules.(1, 2) These T cells are specific for proline- and glutamine-rich gluten peptides that are resistant to proteolysis and that have been become deamidated by the enzyme transglutaminase 2 (TG2). Strikingly, celiac disease patients produce antibodies to this same enzyme when exposed to dietary gluten. Here we discuss how the new insight in the pathogenesis has lead to development of new diagnostics and nourished research into novel treatments.

Functional bowel disease and functional abdominal pain

Article

Full-text available

Oct 1999

The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient's pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.

In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope

Article

Full-text available

Apr 2000

Celiac disease (CD) is an increasingly diagnosed enteropathy (prevalence, 1:200-1:300) that is induced by dietary exposure to wheat gliadins (as well as related proteins in rye and barley) and is strongly associated with HLA-DQ2 (alpha1*0501, beta1*0201), which is present in over 90% of CD patients. Because a variety of gliadin peptides have been identified as epitopes for gliadin-specific T-cell clones and as bioactive sequences in feeding studies and in ex vivo CD intestinal biopsy challenge, it has been unclear whether a 'dominant' T-cell epitope is associated with CD. Here, we used fresh peripheral blood lymphocytes from individual subjects undergoing short-term antigen challenge and tissue transglutaminase-treated, overlapping synthetic peptides spanning A-gliadin to demonstrate a transient, disease-specific, DQ2-restricted, CD4 T-cell response to a single dominant epitope. Optimal gamma interferon release in an ELISPOT assay was elicited by a 17-amino-acid peptide corresponding to the partially deamidated peptide of A-gliadin amino acids 57-73 (Q65E). Consistent with earlier reports indicating that host tissue transglutaminase modification of gliadin enhances gliadin-specific CD T-cell responses, tissue transglutaminase specifically deamidated Q65 in the peptide of A-gliadin amino acids 56-75. Discovery of this dominant epitope may allow development of antigen-specific immunotherapy for CD.

Gluten challenge in coeliac disease reveals a single transglutaminase-modified peptide as the dominant T cell epitope in A-gliadin

Article

Apr 2000

Reply to: gluten ataxia 'in perspective'

Article

Jan 2003

Clinical, radiological, neurophysiological and neuropathological characteristics of gluten ataxia

Article

Jan 2010

"Gluten-sensitive diarrhea without evidence of celiac disease"

Article

Aug 1981
GASTROENTEROLOGY

Intolerance to Cereals Is Not Specific for Coeliac Disease

Article

Jan 2000

K. Kaukinen, K. Turjanmaa, M. Mäki

Autism and Schizophrenia: Intestinal Disorders

Article

Jan 2000
NUTR NEUROSCI

We examined Dohan's hypothesis that schizophrenia is associated with the absorption of "exorphins" contained in gluten and casein. In addition, because of the work of Reichelt et al. (Reichelt, K.L., Saelid, G., Lindback, J. and Orbeck, H. (1986) Biological Psychiatry 21:1279-1290) and Rodriguez et al. (Rodriguez, Trav, A.L., Barreiro Marin, P., Galvez, Borrero, I.M., del Olmo Romero-Nieva, F. and Diaz Alvarez, A. (1994) Journal of Nervous and Mental Disease Aug; 182(8): 478-479), we carried out similar studies on a group of children with autism. In both syndromes we found similar patterns of peptide containing peaks (Ninhydrin positive) after molecular screening with Sephadex G-15. Immunoglobulin assay of IgA and IgG against glia-din and casein in serum was done. High titer IgG antibodies to gliadin were found in 87% of autistic and 86% of schizophrenic patients and high titer IgG antibodies to bovine casein were found in 90% of autistic and in 93% of schizophrenic patients. High titer IgA antibodies to gluten or casein were found in 30% of children with autism while in schizophrenic patients 86% had elevated IgA antibodies to gluten and 67% to casein; some normal children and adults have these antibodies but only in trace amounts. When schizophrenic patients were treated with dialysis or a gluten-casein free diet, or both (Cade, R., Wagemaker, H., Privette, R.M., Fregly, M., Rogers, J. and Orlando, J. (1990) Psychiatry: A World Prespective 1: 494-500) peptiduria and Brief Psychiatric Rating Scores fell while abnormal behavior diminished. A gluten-casein free diet was accompanied by improvement in 81% of autistic children within 3 months in most of the behavior categories. Our data provide support for the proposal that many patients with schizophrenia or autism suffer due to absorption of exorphins formed in the intestine from incomplete digestion of gluten and casein.

Sporadic cerebellar ataxia associated with gluten sensitivity

Article

May 2001
BRAIN

K. Burk

A total of 104 patients with sporadic cerebellar ataxia were tested for antigliadin and antiendomysium antibodies. Twelve individuals (11.5%) with gluten sensitivity underwent duodenal biopsy and extensive clinical, electrophysiological, neuropsychological, radiological and laboratory investigations including human leucocyte antigen (HLA) typing. Two patients showed typical changes of gluten-sensitive enteropathy with crypt hyperplasia and mucosal flattening. In five patients, the intraepithelial lymphocyte count was elevated. Sporadic ataxia with gluten sensitivity was found to be tightly linked to the HLA DQB1*0201 haplotype (70%). Neurological symptoms were not related to hypovitaminosis or inflammatory CSF changes. The clinical syndrome was dominated by progressive cerebellar ataxia with ataxia of stance and gait (100%), dysarthria (100%) and limb ataxia (97%). Oculomotor abnormalities were gaze-evoked nystagmus (66.7%), spontaneous nystagmus (33.3%), saccade slowing (25%) and upward gaze palsy (16.7%). Extracerebellar features also included deep sensory loss (58.3%), bladder dysfunction (33.3%) and reduced ankle reflexes (33.3%). In accordance with clinical findings, electrophysiological investigations revealed prominent axonal neuropathy with reduced amplitudes (50%) and abnormal evoked potentials (58.3%). On neuropsychological testing, patients presented with moderate verbal memory and executive dysfunction. All patients had evidence of cerebellar atrophy on MRI. We conclude that sporadic ataxia may be associated with positive antibodies against gliadin. Nevertheless, mucosal pathology does not represent an obligatory condition of ataxia with gluten sensitivity. The fact that the disease is strongly associated with the same HLA haplotypes found in coeliac disease not only demonstrates coeliac disease and ataxia with gluten sensitivity to be part of the same disease entity but supports the hypothesis of an immunological pathogenesis of cerebellar degeneration.

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: Disappointing in clinical practice

Article

Apr 1999

Kamran Rostami

OBJECTIVE:We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives.METHODS:The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2–76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy).RESULTS:The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA.CONCLUSIONS:Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

Awareness of gluten-related disorders: A survey of the general public, chefs and patients

Article

Oct 2011

Background & aims We sought to establish the level of knowledge of celiac disease (CD) and gluten sensitivity (GS) among the general public and chefs, and to compare dining habits of people with CD and the general public. Methods Surveys assessing knowledge of CD and GS as well as dining habits were administered through an Internet survey tool or face-to-face. The chef survey also assessed training/education. Results Among 861 persons from the general public 47% had heard of CD, 67% of GS and 88% of peanut allergy. Chefs were more likely than the general public to have heard of CD (77% vs. 47%, p < 0.0001), though greater proportions in both groups had heard of GS (89% vs. 67%, p < 0.0001). 63% of patients (n = 790) reported that they avoid restaurants because of the gluten-free diet and ate take-out food and restaurant food significantly less often than the general public. Trained chefs had more knowledge than untrained chefs (83% vs. 52%, p < 0.0001). There was a direct relationship between the average check price and chefs’ awareness (<

25: 64% vs. >

65: 94%, p < 0.0001). Conclusions Awareness of gluten-related issues was prominent. Surprisingly, both the public and chefs were more likely to have heard of GS than CD. Most with CD avoid restaurants, and eat outside the home less frequently than the general public. Knowledge of CD among chefs exceeds that of the general public, but varies considerably.

Gluten ataxia 'in perspective' - Reply

Article

Sep 2003
BRAIN

Marios Hadjivassiliou

We note Dr Wills’ and Dr Unsworth’s continued scepticism at the concept of gluten ataxia in the face of overwhelming evidence in its support. We have proposed that IgG antigliadin antibodies are currently the best marker of the whole spectrum of gluten sensitivity although they are not specific for gluten‐sensitive enteropathy. We hope that a better marker of neurological manifestations of gluten sensitivity will come with the identification of the antibodies recognizing neuronal epitopes, such as those on Purkinje cells identified by antibodies in patients with gluten ataxia. This would be analogous to the antiendomysium antibody in cases with gluten‐sensitive enteropathy or epidermal …

Serological Tests in Gluten Sensitivity (Nonceliac Gluten Intolerance)

Article

Dec 2011
J CLIN GASTROENTEROL

To characterize the serological pattern of gluten sensitivity (GS) and to compare it with that found in celiac disease. GS has recently been identified as a new clinical entity included in the spectrum of gluten-related disorders, but it is still lacking of diagnostic markers. Sera from 78 patients with GS and 80 patients with celiac disease were retrospectively assessed for immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA). IgG AGA were positive in 56.4% of GS patients and in 81.2% of celiac patients, with high antibody titers in both groups. IgA AGA were detected in 7.7% of GS patients and in 75% of celiac patients, showing lower enzyme-linked immunosorbent assay activities in GS than those found in celiac disease. Only 1 of the 78 patients with GS was positive for IgG DGP-AGA (detected in 88.7% of patients with celiac disease). IgA tTGA and IgA EmA were negative in all GS patients, whereas their positivity in celiac patients was 98.7% and 95%, respectively. Patients with GS displayed a variegated clinical picture with intestinal and extraintestinal symptoms (abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia) together with normal or mildly abnormal small intestinal mucosa. The serological pattern of GS is characterized by IgG AGA positivity in more than half of cases associated to IgA AGA in a few patients, but without EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.

Diagnosis, Comorbidities, and Management of Irritable Bowel Syndrome in Patients in a Large Health Maintenance Organization

Article

Aug 2011

Irritable bowel syndrome (IBS) imposes significant clinical and economic burdens. We aimed to characterize practice patterns for patients with IBS in a large health maintenance organization, analyzing point of diagnosis, testing, comorbidities, and treatment. Members of Kaiser Permanente Northern California who were diagnosed with IBS were matched to controls by age, sex, and period of enrollment. We compared rates of testing, comorbidities, and interventions. From 1995-2005, IBS was diagnosed in 141,295 patients (mean age, 46 years; standard deviation, 17 years; 74% female). Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower endoscopy did not usually precede IBS diagnosis. Patients with IBS were more likely than controls to have blood, stool, endoscopic, and radiologic tests and to undergo abdominal or pelvic operations (odds ratios, 1.5-10.7; all P < .0001). Only 2.7% were tested for celiac disease, and only 1.8% were eventually diagnosed with inflammatory bowel disease. Chronic pain syndromes, anxiety, and depression were more common among IBS patients than among controls (odds ratios, 2.7-4.6; all P < .0001). Many patients with IBS were treated with anxiolytics (61%) and antidepressants (55%). Endoscopic and radiologic testing was most strongly associated with having IBS diagnosed by a gastroenterologist. Psychotropic medication use was most strongly associated with female sex. In a large, managed care cohort, most diagnoses of IBS were made by generalists, often without endoscopic evaluation. Patients with IBS had consistently higher rates of testing, chronic pain syndromes, psychiatric comorbidity, and operations than controls. Most patients with IBS were treated with psychiatric medications.

Persistently positive gliadin antibodies without transglutaminase antibodies in the elderly: Gluten intolerance beyond coeliac disease

Article

Jun 2011

The specificity of the conventional gliadin antibody test is considered low. We explored whether gliadin antibody(AGA)-positivity without tissue transglutaminase antibodies (tTGA) is persistent in the elderly population and whether such positivity indicates overt or potential coeliac disease in genetically predisposed individuals. AGA and tissue transglutaminase antibody were measured in 2089 elderly individuals twice with a three-year interval. AGA-positive but tissue transglutaminase antibody-negative subjects with coeliac-type human leucocyte antigen (HLA) were examined and underwent gastroduodenal endoscopy (cases). Small-bowel mucosal villous morphology and densities of CD3+ and γδ+ intraepithelial lymphocytes and the occurrence of tissue transglutaminase-specific IgA deposits were analysed. Randomly selected persistently AGA-negative age- and sex-matched subjects served as controls. AGA-positivity was persistent in 81% of those initially positive. Amongst the 49 clinically studied and 36 endoscopied cases only one (2.8%) had coeliac disease. Many (54%) showed signs of inflammation in the biopsy, without villous atrophy. Coeliac-type HLA was not over-represented in the persistently AGA-positive compared to the general population. Persistently AGA-positive coeliac-type HLA-positive subjects had more gastrointestinal symptoms than AGA-negative controls. AGA-positivity is often persistent. Overt coeliac disease is seldom found behind persistent AGA-positivity, but this characteristic is associated with mucosal inflammation and gastrointestinal symptoms at least in HLA-positive individuals.

Diagnosis of Food Allergy: Epicutaneous Skin Tests, In Vitro Tests, and Oral Food Challenge

Article

Oct 2010
CURR ALLERGY ASTHM R

Food allergy is becoming an increasingly common diagnosis. Because of this increase in prevalence, it is imperative that physicians evaluating patients with possible adverse reactions to foods understand the currently available assays and how they should best be used to accurately diagnose the disease. Simple tests such as skin prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests, which measure sensitization and not clinical allergy, are not without pitfalls, and their utility must be appreciated to avoid over- and underdiagnosis. Although the physician-supervised oral food challenge remains the gold standard for food allergy diagnosis, a careful medical history paired with SPT and serum food-specific IgE testing often can provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT and serum food-specific IgE levels, as well as examine atopy patch testing and other emerging tests, such as component-resolved diagnostics and the basophil activation test. Finally, we describe the use of the double-blind, placebo-controlled oral food challenge as the current gold standard for food allergy diagnosis.

Markers of Gluten Sensitivity and Celiac Disease in Recent-Onset Psychosis and Multi-Episode Schizophrenia

Article

Jul 2010

Increased immune sensitivity to gluten has been reported in schizophrenia. However, studies are inconsistent about this association. The sample of 471 individuals included 129 with recent-onset psychosis, 191 with multi-episode schizophrenia, and 151 controls. Immunoglobulin (Ig)G and IgA antibodies to gliadin and to tissue transglutaminase, and IgG antibodies to deamidated gliadin were measured. Quantitative levels of antibodies in the psychiatric groups were compared with controls. All participants were categorized as to whether their levels of antibodies met standardized cutoffs for celiac disease. HLA DQ2 and HLA DQ8 alleles were detected by real-time polymerase chain reaction. Individuals with recent-onset psychosis had increased levels of IgG (odds ratio [OR] 5.50; 95% confidence interval [CI] 2.65-11.42) and IgA (OR 2.75; 95% CI 1.31-5.75) antibodies to gliadin compared with control subjects. Individuals with multi-episode schizophrenia also had significantly increased levels of IgG antibodies to gliadin (OR 6.19; 95% CI 2.70-14.16). IgG antibodies to deamidated gliadin and IgA antibodies to tissue transglutaminase were not elevated in either psychiatric group, and fewer than 1% of individuals in each of the groups had levels of these antibodies predictive of celiac disease. There were no significant differences in the distribution of the HLA DQ2/8 alleles among the groups. Individuals with recent-onset psychosis and with multi-episode schizophrenia who have increased antibodies to gliadin may share some immunologic features of celiac disease, but their immune response to gliadin differs from that of celiac disease.

Novel Immune Response to Gluten in Individuals with Schizophrenia

Article

Sep 2009

A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes.

Double-blind, placebo-controlled food challenge in adults in everyday clinical practice: A reappraisal of their limitations and real indications

Article

Jun 2009
CURR OPIN ALLERGY CL

The double-blind, placebo-controlled food challenge (DBPCFC) is widely considered as the 'gold standard' for the diagnosis of food allergy. However, in adult patients, this procedure is rather rarely performed outside the academic context. This review article aims to reappraise the pros and cons of DBPCFC and to elicit some critical thoughts and discussions about the real indications of this diagnostic procedure in adult patients in everyday practice. There are many data showing that the DBPCFC poses a number of critical problems that are difficult to overcome in normal outpatient clinics and hospitals, and that are generally not addressed in most articles dealing with this issue. Performing DBPCFC poses a number of practical problems and has several pitfalls, which make its routine use in normal clinical settings generally impossible. This review article shows that the need for this procedure in adult patients seems in effect very little and specifies new, more limited indications to its use in everyday practice. Further, it suggests a role for the open challenge, which lacks several of the disadvantages of DBPCFC.

The Gluten-Free, Casein-Free Diet in Autism: An Overview With Clinical Implications

Article

Dec 2008

Jennifer H Elder

The prevalence of classic autism and autism spectrum disorder (ASD) appears to be on the rise, and to date, there remains no clear etiology or cure. Out of desperation, many families are turning to new therapies and interventions discovered through various media sources and anecdotal reports from other parents. Unfortunately, many of these newer, well-publicized interventions have little empirical support. One of the most popular yet currently scientifically unproven interventions for ASD is the gluten-free, casein-free (GFCF) diet. Clinicians working with families of individuals with ASD are often asked for advice and find themselves unable to offer the most up-to-date and scientifically credible information. This article provides an overview of ASD and the GFCF diet, a summary and critique of current research findings, recommendations for future research, and practical advice for families to use in deciding if a trial of the GFCF diet is in the best interest of their child and family.

Gastrointestinal Symptoms in Children with an Autism Spectrum Disorder and Language Regression

Article

Jan 2009
PEDIATR NEUROL

Few studies have compared gastrointestinal problems in children with an autism spectrum disorder with and without a history of language regression. A cross-sectional study was conducted with structured interviews in 100 children with autism spectrum disorder, using a gastrointestinal questionnaire and a familial autoimmune questionnaire. By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%, P = 0.006) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%, P = 0.001) and of rheumatoid arthritis (30% vs 11%, P = 0.03). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%, P = 0.001) than in those without. An association was observed between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Additional studies are needed to examine a possible shared autoimmune process.

Comparison of Commercially Available Serologic Kits for the Detection of Celiac Disease

Article

Sep 2008
J CLIN GASTROENTEROL

The sensitivity and specificity of current antihuman tissue transglutaminase (tTG) IgA assays used to detect celiac disease reportedly approach 100%. In addition, the sensitivity of new generation deamidated gliadin peptide (alpha-DGP) antibody assays has also been reported to be similar to the tTG IgA assays. In routine clinical practice, however, the sensitivities and specificities of these tests for diagnosing celiac disease seem to be lower. We analyzed sensitivities and specificities of 4 IgA tTG and 3 deamidated gliadin peptide (alpha-DGP) kits. The performance of 4 tTG IgA assays, A: Inova (Hu red blood cell), B: Binding site (rHu Ag), C: Eurospital (rHu Ag), D: Immco (rHu Ag) and 3 Inova alpha-DGP assays, E: alpha-DGP-IgA, F: alpha-DGP-IgG, and G: alpha-DGP-IgA+G was evaluated using sera from different subsets of celiac disease patients and controls; group 1: active celiac disease n=28, group 2: gluten-free diet n=54, group 3: healthy controls n=40, group 4: disease controls n=57(Crohn's disease n=17, chronic hepatitis n=40). Using the manufacturer's cut-off values, the sensitivities and specificities of different kits ranged from 71.4% to 96.4% and 87.5% to 100%, respectively. When group 1 was compared with disease controls, sensitivities remained the same but specificities decreased. Receiver operating characteristic plot derived cut-off values modified decision thresholds in all assays except kit (G). Kappa analysis demonstrated variable degrees of agreement. All assays demonstrated higher sensitivities for patients with higher grades of villous atrophy. Overall sensitivity was at or below 90%, which is lower than that reported in the literature. Performance of the recombinant and red blood cell antigen-based tTG assays was similar, whereas the alpha-DGP assays demonstrated lower values. Receiver operating characteristic plot derived cut-off values altered test results. Many factors affect the results of these tests and clinicians should be aware of their limitations.

Response of intestinal mucosa to gluten challenge in autistic subjects

Article

Nov 1979

Eight autistic patients with steatorrhoea, hypocalciuria, and alleged behavioural improvements on gluten restriction, were fed ordinary diets plus 20 g gluten/day for 4 weeks. None of the patients had any significant change in body-weight or bowel habit as a result of gluten challenge, nor were any histological abnormalities detected on jejunal biopsy. The data suggest that the steatorrhoea and hypocalciuria seen in some autistic subjects cannot be accounted for by the presence of coeliac disease. Furthermore, these patients should not be confined to gluten-free diets, unless rigorous behavioural studies demonstrate a statistically significant improvement in behaviour as a result of the diet, or deterioration during challenge.

Coeliac disease and schizophrenia

Article

Feb 1971

D N Challacombe

Coeliac disease and Schizophrenia

Article

Aug 1973

F C Dohan

Agglutinating activity of gliadin-derived peptides from wheat: Implications for coeliac disease pathogenesis

Article

Jul 1984

The PT-digest of bread wheat gliadin was very active in agglutinating undifferentiated human K562(S) cells. This activity was quantitatively, but not qualitatively, similar to that of Con A or WGA. Moreover, Con A-induced cell agglutination was inhibited by mannan and mannose, WGA-induced agglutination by NAG only, and cell agglutination induced by bread wheat gliadin peptides was inhibited by each of these three saccharides. Not only was mannan the most active saccharide in preventing cell agglutination induced by bread wheat gliadin peptides, but it was also able to dissociate agglutinated cells. As compared to the PT- digest of whole bread wheat gliadin, the digest obtained from purified A-gliadin was tenfold more active. The PT-digest of durum wheat gliadin did not show any agglutinating activity.

Incomplete Absorption of the Carbohydrate in All-Purpose Wheat Flour

Article

May 1981

Malabsorption of the carbohydrate lactose is a common cause of flatulence, abdominal discomfort, and diarrhea in otherwise healthy persons. The possibility that such symptoms could result from malabsorption of the other major dietary carbohydrates (sucrose or starch) has received little consideration since these carbohydrates are assumed to be completely absorbed in health. The authors measured breath hydrogen to assess the absorption of the carbohydrate in white, all-purpose wheat flour. These studies demonstrate that nearly all normal subjects fail to absorb an appreciable portion of this form of starch, possibly because of an interaction between the starch and protein moieties of wheat flour.

Celiac disease and schizophrenia

Article

Jun 1980

F C Dohan

Cooper BT, Holmes GK, Ferguson RA, et al .Gluten-sensitive diarrhea without evidence of celiac disease

Article

Dec 1980
GASTROENTEROLOGY

Eight adult female patients suffering from abdominal pain and chronic diarrhea which was often incapacitating and frequently nocturnal, had dramatic relief on a gluten-free diet and return of symptoms after gluten challenge. Previous nonspecific measures and a milk-free diet were ineffective. Multiple jejunal biopsies showed minor, but significant changes in cellularity which returned to normal on the gluten-free diet. Apart from a slight increase in jejunal cellularity, no immunological abnormalities were found after gluten challenge. Steatorrhea or other biochemical defects, common in celiac disease, were not found. It was concluded that these patients had a gluten-sensitive diarrhea, but had no evidence of celiac disease.

In siblings of celiac children, rectal gluten challenge reveals gluten sensitization not restricted to celiac HLA

Article

Sep 1996
GASTROENTEROLOGY

Inflammatory changes in the rectum of patients with celiac disease after local instillation of gluten have been reported. The aim of this study was to examine rectal mucosa after local gluten challenge in children with celiac disease and their siblings. Rectal biopsy specimens were obtained before and 6 hours after rectal challenge with a peptictryptic digest of gliadin in 33 children with treated celiac disease, 12 controls, and 19 siblings of children with celiac disease. Epithelium and lamina propria volumes were determined, and CD3+ and gamma delta + lymphocytes were counted. After local instillation of gliadin, a significant increment in the absolute number of intraepithelial lymphocytes was noted in patients with celiac disease but not in controls. Immunohistochemical analysis showed a significant increase in CD3+ and gamma delta + cells, with the gamma delta/CD3 ratio remaining unchanged after challenge. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis was used to classify 6 of 13 siblings as having celiac disease. The positivity was not associated with the presence of the heterodimer encoded by the DQA*0501 DQB1*0201 alleles in any of the siblings. All patients with celiac disease were identified by rectal gluten challenge. Approximately half of the siblings reacted to rectal instillation of gluten. The genetic background of such sensitization to gluten remains to be elucidated.

Food-induced Type 1 Diabetes in the BB Rat

Article

Dec 1996

Fraser W Scott

Autism and celiac disease: Failure to validate the hypothesis that a link might exist

Article

Aug 1997
BIOL PSYCHIAT

Autism is a heterogeneous condition and the possible pathogenic role of several different factors has been postulated. Association between celiac disease and neurological manifestations such as drug resistant epilepsy and cerebral calcifications is well known. Some authors in the past also reported the existence of a linkage with autism. On the basis of these observations, we have evaluated 120 patients with celiac disease diagnosed at the Pediatric Clinic of the University of Catania, Italy, in order to identify behavioral problems and autistic features: there were 20 controls for this part of the study. At the same time, AGA and AEMAb were assayed in 11 patients with infantile autism and 11 age- and sex-matched controls. No celiac case was detected among the group of autistic patients and, although two of them had slightly increased levels of AGA IgG and AEMAb, subsequent antibodies determinations and jejunal biopsies gave normal results. Moreover none of the celiac patients had a positive DSM-III-R test for infantile autism.

Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia

Article

Dec 1998

Ataxia is the commonest neurological manifestation of coeliac disease. Some individuals with genetic susceptibility to the disease have serological evidence of gluten sensitivity without overt gastrointestinal symptoms or evidence of small-bowel inflammation. The sole manifestation of disease in such patients may be ataxia. We describe the clinical, radiological, and neurophysiological features of this disorder. Patients with ataxia attending the neurology outpatient clinics at the Royal Hallamshire Hospital, Sheffield, UK, were screened for gluten sensitivity as shown by the titre of antibody to gliadin. Those with other causes of ataxia were excluded. We carried out clinical, neurophysiological, neuroradiological, and, in two cases, neuropathological examinations. 28 patients with gluten ataxia were identified. All had gait ataxia and most had limb ataxia. Those with more severe gait ataxia had longer disease duration. No patient had tremor or other extrapyramidal features. 19 patients showed some form of peripheral neuropathy on neurophysiological examination. 16 patients had no gastrointestinal symptoms. Distal duodenal biopsy showed lymphocytic infiltration in two patients, and changes compatible with coeliac disease in 11. Six patients had evidence of cerebellar atrophy on magnetic-resonance imaging. Necropsy was done on two patients who died; there was lymphocytic infiltration of the cerebellum, damage to the posterior columns of the spinal cord, and sparse infiltration of the peripheral nerves. Gluten sensitivity is an important cause of apparently idiopathic ataxia and may be progressive. The ataxia is a result of immunological damage to the cerebellum, to the posterior columns of the spinal cord, and to peripheral nerves. We propose the term gluten ataxia to describe this disorder.

Sensitivity of Antiendomysium and Antigliadin Antibodies in Untreated Celiac Disease: Disappointing in Clinical Practice

Article

May 1999

We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives. The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy). The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA. Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

Gluten-free diet prevents diabetes in NOD mice

Article

Sep 1999

Epidemiological as well as animal studies have shown that environmental factors such as nutrition contribute to the development of diabetes. In this study we investigated whether the early introduction of a gluten-free diet can influence the onset and/or incidence of diabetes, as well as insulitis and the number of gut mucosal lymphocytes, in non-obese diabetic (NOD) mice. Gluten-free and standard Altromin diets (with the same milk protein and vitamin content) were given to breeding pairs of NOD mice as well as to the first generation of NOD female mice, which were then observed for 320 days. A substantially lower diabetes incidence (chi(2)=15.8, p=0.00007) was observed in NOD mice on the gluten-free diet (15%, n=27) compared to mice on the standard diet (64%, n=28). In addition, mice on the gluten-free diet developed diabetes significantly later (244+/-24 days SEM) compared to those on the standard diet (197+/-8 days, p=0.03). No differences in the number of CD3(+), TCR-gammadelta(+), IgA(+), and IgM(+) cells in the small intestine were observed. We showed that gluten-free diet both delayed and to a large extent prevented diabetes in NOD mice that have never been exposed to gluten.

Induction of apoptosis in CaCo-2 cells by wheat gliadin peptides

Article

May 2000
TOXICOLOGY

Recent experimental evidence suggests that enterocyte apoptosis is greater than hitherto assumed and may be responsible for villous atrophy in coeliac disease. We have previously demonstrated that a small peptide (M.W. 1157.5 Da), identified as the sequence H(2)N-gln-gln-pro-gln-asp-ala-val-gln-pro-phe-COOH from durum wheat gliadin, is able to prevent K 562 (S) cell agglutination induced by the peptic-tryptic digests (PT) of prolamin fractions from the cereals which are not tolerated in coeliac disease (i.e. bread wheat, rye, barley and possibly oats), and toxic A-gliadin peptides in coeliac disease. In the present study we have investigated the effects of the bread wheat gliadin digest (PT) on apoptosis of Caco-2 cells and whether the '1157.5' Da peptide may in any way interfere with them. We evaluated both earlier biochemical and later morphological nuclear apoptotic events in the human colon adenocarcinoma cell line Caco-2. After 48 h exposure to the PT gliadin digest and the '1157.5' Da peptide, apoptosis was detected both for the early-stage apoptotic cells (adherent cells) and the late-stage apoptotic ones (detached cells which were floating in the culture medium). Exposure to the PT gliadin digest resulted in a high percentage of adherent cells that underwent cell death by apoptosis (about 30%), independent of the concentration range used; while the presence in the culture medium of peptide '1157.5' Da determined complete inhibition of cell death. On the other hand, morphological nuclear modifications observed in the floating cells showed a difference in the rate of the apoptosis dependent on the PT concentration, with partial protection in the presence of the peptide. These findings show an action of bread wheat gliadin peptides leading to cell death by apoptosis in the Caco-2 cell line and that the '1157.5' Da peptide is capable of preventing such an effect.

Intolerance to cereals is not specific for celiac disease

Article

Oct 2000

Abdominal complaints after ingestion of cereals are not uncommon. We assessed how reliable such a history is as a marker for the presence of overt coeliac disease, and whether we should also take into account latent coeliac disease and cereal allergy. The study group comprised 93 consecutive adults from health centres spontaneously reporting abdominal symptoms after consumption of cereals. Small bowel mucosal morphology, CD3+, alphabeta+ and gammadelta+ intraepithelial lymphocytes (IELs), HLA DQ alleles and serum IgA-class endomysial (EmA), tissue transglutaminase (tTg) and gliadin (AGA) antibodies were determined. Skin prick and patch tests and serum radioallergosorbent tests for cereals were carried out. Thirty non-coeliac adults served as biopsy controls. Eight (9%) patients had coeliac disease and one mild partial villous atrophy. Altogether 17 had an increased density of gamma delta+ IELs without atrophy. However, only seven (8%) showed evidence of latent coeliac disease, i.e. both an increase in gammadelta+ IELs and the presence of coeliac disease-type HLA. One or more of the allergy tests for cereals was positive in 19; 9 adopted a gluten-free diet and abdominal symptoms were alleviated in all. In non-coeliac patients, serum EmA and tTg tests were negative in all, whereas AGA was seen in 40%. Intolerance to cereals is not a specific sign of overt or latent coeliac disease. All experimental dietary interventions before proper diagnosis of coeliac disease are therefore to be discouraged. Allergy to cereals, on the other hand, should be considered even in adults.

Homemade Gluten-Free Pasta Is as Well or Better Digested Than Gluten-Containing Pasta

Article