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Sample records for celiac disease-related gluten

  1. Celiac disease and new diseases related to gluten

    PubMed

    Jiménez Ortega, Ana Isabel; Martínez García, Rosa María; Quiles Blanco, María José; Majid Abu Naji, Jamil Abdel; González Iglesias, María José

    2016-07-12

    Celiac disease is the most common chronic intestinal disease. Nowadays it´s known that this is a multisistemic pathology of immune mechanism, triggered by gluten, which occurs in genetically susceptible individuals. It affects approximately 1% of the world population, which is a very high prevalence, affects all age groups and has symptoms both digestive and extra-digestive. Since it is a disease that requires maintaining a gluten-free diet and medical monitoring for life, it is important to know it and establish its diagnosis properly. Along with celiac disease a number of new diseases related to gluten are diagnosed increasingly, including the non celiac gluten sensitivity or wheat allergy. The suffering of celiac disease, or other related diseases, by conditioning diet changes of the affected individual, it may be associated with nutritional imbalances that need to monitor and try to solve. Therefore patients with this problem need special nutritional advice.

  2. In search of tetraploid wheat accessions reduced in celiac disease-related gluten epitopes.

    PubMed

    van den Broeck, Hetty; Hongbing, Chen; Lacaze, Xavier; Dusautoir, Jean-Claude; Gilissen, Ludovicus; Smulders, Marinus; van der Meer, Ingrid

    2010-11-01

    Tetraploid wheat (durum wheat) is mainly used for the preparation of pasta. As a result of breeding, thousands of tetraploid wheat varieties exist, but also tetraploid landraces are still maintained and used for local food preparations. Gluten proteins present in wheat can induce celiac disease, a T-cell mediated auto-immune disorder, in genetically predisposed individuals after ingestion. Compared to hexaploid wheat, tetraploid wheat might be reduced in T-cell stimulatory epitopes that cause celiac disease because of the absence of the D-genome. We tested gluten protein extracts from 103 tetraploid wheat accessions (obtained from the Dutch CGN genebank and from the French INRA collection) including landraces, old, modern, and domesticated accessions of various tetraploid species and subspecies from many geographic origins. Those accessions were typed for their level of T-cell stimulatory epitopes by immunoblotting with monoclonal antibodies against the α-gliadin epitopes Glia-α9 and Glia-α20. In the first selection, we found 8 CGN and 6 INRA accessions with reduced epitope staining. Fourteen of the 57 CGN accessions turned out to be mixed with hexaploid wheat, and 5 out of the 8 selected CGN accessions were mixtures of two or more different gluten protein chemotypes. Based on single seed analysis, lines from two CGN accessions and one INRA accession were obtained with significantly reduced levels of Glia-α9 and Glia-α20 epitopes. These lines will be further tested for industrial quality and may contribute to the development of safer foods for celiac patients.

  3. A modified extraction protocol enables detection and quantification of celiac disease-related gluten proteins from wheat.

    PubMed

    van den Broeck, Hetty C; America, Antoine H P; Smulders, Marinus J M; Bosch, Dirk; Hamer, Rob J; Gilissen, Ludovicus J W J; van der Meer, Ingrid M

    2009-04-01

    The detection, analysis, and quantification of individual celiac disease (CD) immune responsive gluten proteins in wheat and related cereals (barley, rye) require an adequate and reliable extraction protocol. Because different types of gluten proteins behave differently in terms of solubility, currently different extraction protocols exist. The performance of various documented gluten extraction protocols is evaluated for specificity and completeness by gel electrophoresis (SDS-PAGE), immunoblotting and RIDASCREEN Gliadin competitive ELISA. Based on these results, an optimized, two-step extraction protocol has been developed.

  4. [Non-celiac gluten sensitivity].

    PubMed

    Hoffmanová, Iva; Sánchez, Daniel

    2015-03-01

    Non-celiac gluten sensitivity has recently been recognized by the scientific community as a part of gluten-related disorders, and is defined as a condition with gastrointestinal and/or extra-intestinal symptoms triggered by gluten ingestion in the absence of celiac disease and wheat allergy. Currently, there is no specific serological marker and non-celiac gluten sensitivity remains a diagnosis of exclusion: testing for celiac disease and wheat allergy must be negative, symptoms must improve with a gluten-free diet, and diagnosis must be confirmed by the gluten challenge. In this article, we discuss current knowledge of pathophysiology, clinical and epidemilogical spectrum, diagnosis, and treatment of NCGS.

  5. Non Celiac Gluten Sensitivity.

    PubMed

    Bardella, Maria Teresa; Elli, Luca; Ferretti, Francesca

    2016-12-01

    A new syndrome responding to gluten-free diet and defined non-celiac gluten sensitivity entered the spectrum of gluten-related disorders, together with celiac disease and wheat allergy. However, its definition, prevalence, diagnosis, pathogenesis, treatment, and follow up are still controversial. The purpose of the review is to summarize the evidence and problems emerging from the current literature. Direct implication of gluten in the onset of symptoms is often unproved as a low fermentable oligo-, di- and mono-saccharides and polyols diet or other components of cereals as wheat amylase trypsin inhibitor could be similarly involved. To date, no specific biomarkers or histological abnormalities confirm diagnosis, and only the self-reported response to gluten-free diet as well as a positive double blind placebo-gluten challenge characterizes these non-celiac, non-wheat allergic patients. Critical revision of published studies can offer practical indications in approaching this clinical topic and useful suggestions to standardize scientific researches.

  6. [Celiac disease and "gluten sensitivity"].

    PubMed

    Tronconi, G M; Parma, B; Barera, G

    2010-01-01

    It is known that celiac disease is characterized by a huge variety of clinical forms ranging from classical ones to silent forms, potential ones and to an increased number of cases of gluten-sensitivity. The latter is an abnormal non-allergic sensibility to gluten. Clinical manifestations can be very different without a severe intestinal damage (Marsh/Oberhuber 0-I) and this condition seems to benefit from a gluten free diet. Cases of gluten-sensitivity appear very interesting in the search of histological markers with elevated specificity, which are able to identify slight and early gluten dependent enteropathy, especially in at risk patients for celiac disease even before classical autoantibodies appear: for instance, this is the case of intraepithelial lymphocytes T-cell receptor gamma delta and mucosal deposits of class IgA anti transglutaminase antibodies. Other studies are investigating transglutaminase isoenzimes (different from tissue one), that can be identified in patients with gluten dependent symptoms without classical autoantibodies. Forms of gluten allergy have a different pathogenesis from celiac disease and are represented by "backer's asthma" or by classical allergy to wheat proteins. Clinical manifestations can vary from anaphylactic reactions to dermatological, respiratory and intestinal symptoms. Also in these cases the therapeutic approach is based on gluten free diet.

  7. Non-celiac gluten hypersensitivity.

    PubMed

    Ashat, Munish; Kochhar, Rakesh

    2014-01-01

    There has been an increasing interest in non-celiac gluten sensitivity (NCGS) in recent years. The condition is characterized by both gastrointestinal and extra-intestinal symptoms that respond to gluten withdrawal. Most of the symptoms are subjective and for many years such patients remain in a diagnostic dilemma. Although symptomalogy is similar to irritable bowel syndrome (IBS), NCGS is now regarded as a distinct clinical entity. However, the disease pathology is not well elucidated and our knowledge of NCGS is still very rudimentary. This review highlights the importance of this new clinical entity, outlines its pathological mechanisms and suggests a diagnostic algorithm for its management.

  8. Quick Start Gluten Free Diet Guide for Celiac Disease and Non Celiac Sensitivity

    MedlinePlus

    ... Free Diet Guide for Celiac Disease & Non-Celiac Gluten Sensitivity The Quick Start Guide is designed to provide ... with celiac disease, dermatitis herpetiformis and non-celiac gluten sensitivity. For more detailed information consult with a dietitian ...

  9. Celiac disease and non-celiac gluten sensitivity.

    PubMed

    Lebwohl, Benjamin; Ludvigsson, Jonas F; Green, Peter H R

    2015-10-05

    Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.

  10. Celiac disease and non-celiac gluten sensitivity

    PubMed Central

    Lebwohl, Benjamin; Ludvigsson, Jonas F

    2015-01-01

    Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population. PMID:26438584

  11. Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity.

    PubMed

    Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa

    2015-06-21

    Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.

  12. Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

    PubMed Central

    Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa

    2015-01-01

    Cereal crops and cereal consumption have had a vital role in Mankind’s history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient’s clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis. PMID:26109797

  13. Celiac Disease and Nonceliac Gluten Sensitivity.

    PubMed

    Watkins, Runa D; Zawahir, Shamila

    2017-06-01

    Gluten-related disorders include celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity. CD is an autoimmune enteropathy caused by damage to small intestinal mucosa when gluten is ingested in genetically susceptible individuals. Currently, the only available treatment of CD is gluten-free diet. Several potential treatments are being researched. Wheat allergy is a hypersensitivity reaction caused by IgE-mediated and/or non-IgE-mediated immune response, and can involve the gastrointestinal tract, skin, or respiratory tract. Nonceliac gluten sensitivity is one of a variety of immunologic, morphologic, or symptomatic manifestations precipitated by ingestion of gluten in individuals in whom CD and wheat allergy are excluded. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Celiac disease and gluten-associated diseases.

    PubMed

    Helms, Steve

    2005-09-01

    Celiac disease develops from an autoimmune response to specific dietary grains that contain gluten. Diagnosis can be made based on the classical presentation of diarrhea, fatty stools, and abdominal bloating and cramping, as well as the presence of specific serum antibodies. In addition, gluten ingestion has increasingly been found to be associated with other conditions not usually correlated with gluten intolerance. The subsequent diversity of the clinical presentation in these cases can complicate decision-making and delay treatment initiation in conditions such as ataxia, headaches, arthritis, neuropathy, type 1 diabetes mellitus, and others. This review explores the etiology and pathology of celiac disease, presents support for the relationship between gluten and other diseases, and provides effective screening and treatment protocols.

  15. Discovery of gluten as the injurious component in celiac disease.

    PubMed

    Goh, Vi Lier; Werlin, Steven L

    2011-04-01

    Celiac disease is a common disorder that was first identified in the early 1900s. Multiple diets were used to treat celiac disease until 1953, when Dicke, Weijers, and van de Kamer identified gluten as the cause of the symptoms. Today, gluten avoidance continues to be the only treatment for patients with celiac disease.

  16. Celiac Disease and Nonceliac Gluten Sensitivity: A Review.

    PubMed

    Leonard, Maureen M; Sapone, Anna; Catassi, Carlo; Fasano, Alessio

    2017-08-15

    The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial). Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, extraintestinal signs or symptoms, or both, suggesting that celiac disease is a systemic disease. Nonceliac gluten sensitivity is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. The clinical variability and the lack of validated biomarkers for nonceliac gluten sensitivity make establishing the prevalence, reaching a diagnosis, and further study of this condition difficult. Nevertheless, it is possible to differentiate specific gluten-related disorders from other conditions, based on currently available investigations and algorithms. Clinicians cannot distinguish between celiac disease and nonceliac gluten sensitivity by symptoms, as they are similar in both. Therefore, screening for celiac disease must occur before a gluten-free diet is implemented, since once a patient initiates a gluten-free diet, testing for celiac disease is no longer accurate. Celiac disease and nonceliac gluten sensitivity are common. Although both conditions are treated with a gluten-free diet, distinguishing between celiac disease and nonceliac gluten sensitivity is important for long-term therapy. Patients with celiac disease should be followed up

  17. [Adult celiac disease(gluten enteropathy].

    PubMed

    Pleşa, Alina; Lepşa, Alina; Crumpei, Felicia

    2002-01-01

    Celiac sprue is a disease in which there is malabsorption of nutrients by that portion of the small intestine which is damaged, a characteristic though not specific lesion of the small intestinal mucosa and prompt clinical improvement following withdrawal of certain cereal grains from the diet. We present a 41 years old patient with a history of diarrhea, treated as enterocolitis for several years, in which the gluten-free diet brought a clinical improvement.

  18. [Irritable bowel syndrome, celiac disease and gluten].

    PubMed

    Mearin, Fermín; Montoro, Miguel

    2014-08-04

    For many years irritable bowel syndrome (IBS) and celiac disease (CD) have been considered 2 completely separate entities, with CD being clearly related to a permanent gluten intolerance and IBS having no relation with gluten ingestion. However IBS and CD symptoms may be indistinguishable, especially when diarrhea, bloating or abdominal pain predominate. In the last decade several studies have shown that the separation between CD and IBS is not so clear. Thus, some patients who have been diagnosed of IBS suffer in fact from CD. In addition, it seems that there is a group of patients who, without having CD, suffer gluten intolerance that cause them digestive symptoms similar to those of IBS. Gluten sensitivity is defined as the spectrum of morphological, immunological and functional abnormalities that respond to a gluten-free diet. This concept includes histological, immunological and clinical manifestations in the absence of evident morphological abnormalities. Therefore, it is mandatory to establish in a scientific way in which patients a gluten-free diet will be beneficial as well as when this is not justified. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  19. Advances in celiac disease and gluten-free diet.

    PubMed

    Niewinski, Mary M

    2008-04-01

    Celiac disease is becoming an increasingly recognized autoimmune enteropathy caused by a permanent intolerance to gluten. Once thought to be a rare disease of childhood characterized by diarrhea, celiac disease is actually a multisystemic disorder that occurs as a result of an immune response to ingested gluten in genetically predisposed individuals. Screening studies have revealed that celiac disease is most common in asymptomatic adults in the United States. Although considerable scientific progress has been made in understanding celiac disease and in preventing or curing its manifestations, a strict gluten-free diet is the only treatment for celiac disease to date. Early diagnosis and treatment, together with regular follow-up visits with a dietitian, are necessary to ensure nutritional adequacy and to prevent malnutrition while adhering to the gluten-free diet for life. The purpose of this review is to provide clinicians with current updated information about celiac disease, its diverse clinical presentation and increased prevalence, the complex pathophysiology and strong genetic predisposition to celiac disease, and its diagnosis. This review focuses in detail on the gluten-free diet and the importance of intense expert dietary counseling for all patients with celiac disease. Recent advances in the gluten-free diet include food allergen labeling as well as the US Food and Drug Administration's proposed definition of the food-labeling term gluten-free. The gluten-free diet is complex and patients need comprehensive nutrition education from a skilled dietitian.

  20. Sources of Gluten

    MedlinePlus

    ... Responsive Celiac Disease Related Conditions Non-Celiac Wheat Sensitivity Resources Symptoms Checklist Adult Follow-Up Checklist Pediatric Follow-Up Checklist Healthcare Practitioner Directory 7-Day Gluten-Free Meal Plan 7-Day Pediatric Gluten-Free ...

  1. Assessing of Celiac Disease and Nonceliac Gluten Sensitivity

    PubMed Central

    Ontiveros, N.; Hardy, M. Y.; Cabrera-Chavez, F.

    2015-01-01

    The publication of papers on the topic of gluten related disorders has substantially increased over the last few years. This has motivated healthcare professionals to pay attention not only to celiac disease and wheat allergy but also to a condition termed nonceliac gluten sensitivity (NCGS). Until now this condition has been diagnosed clinically on the basis of exclusion criteria and clinical response to gluten withdrawal. In addition, recent research in this field has shown that other food components distinct from gluten are implicated in NCGS cases, thereby changing our general understanding of NCGS diagnosis in either individuals on gluten containing diets or those already following a gluten-free diet with no proper diagnostic work-up of celiac disease. With this in mind, the assessment of NCGS will require extensive knowledge of celiac disease manifestations and the laboratory tests commonly performed during diagnosis of celiac disease. PMID:26064097

  2. Assessing of Celiac Disease and Nonceliac Gluten Sensitivity.

    PubMed

    Ontiveros, N; Hardy, M Y; Cabrera-Chavez, F

    2015-01-01

    The publication of papers on the topic of gluten related disorders has substantially increased over the last few years. This has motivated healthcare professionals to pay attention not only to celiac disease and wheat allergy but also to a condition termed nonceliac gluten sensitivity (NCGS). Until now this condition has been diagnosed clinically on the basis of exclusion criteria and clinical response to gluten withdrawal. In addition, recent research in this field has shown that other food components distinct from gluten are implicated in NCGS cases, thereby changing our general understanding of NCGS diagnosis in either individuals on gluten containing diets or those already following a gluten-free diet with no proper diagnostic work-up of celiac disease. With this in mind, the assessment of NCGS will require extensive knowledge of celiac disease manifestations and the laboratory tests commonly performed during diagnosis of celiac disease.

  3. Poorly Responsive Celiac Disease

    MedlinePlus

    ... Responsive Celiac Disease Related Conditions Non-Celiac Wheat Sensitivity Resources Symptoms Checklist Adult Follow-Up Checklist Pediatric Follow-Up Checklist Healthcare Practitioner Directory 7-Day Gluten-Free Meal Plan 7-Day Pediatric Gluten-Free ...

  4. Non-celiac gluten sensitivity: literature review.

    PubMed

    Mansueto, Pasquale; Seidita, Aurelio; D'Alcamo, Alberto; Carroccio, Antonio

    2014-01-01

    A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS. It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients

  5. [A review of diseases related to the intake of gluten].

    PubMed

    Vaquero, Luis; Alvarez-Cuenllas, Begoña; Rodríguez-Martín, Laura; Aparicio, Marta; Jorquera, Francisco; Olcoz, José Luis; Vivas, Santiago

    2015-06-01

    Cereals are considered a basic food. Through the development of cooking, the human being has produced high- gluten-content food, so that it could make the most of its nutritional properties. Wheat is becoming one of the key elements of the Mediterranean diet. Amongst gluten- intake-related pathologies- gluten is present mainly in wheat, barley and rye- celiac disease (CD) is the most well-known. CD is a chronic inflammatory condition which affects gastrointestinal tract which develops in genetically predisposed individuals. The most common manifestation of CD is nutrients malabsorption. This protein trigger other pathology, wheat allergy (WA), which is an adverse immunological effect to gluten due to E immunoglobulin. A recent increased in non celiac gluten sensitivity (NCGS) has also been noticed, defined as the emergence of a range of gluten-intake related symptoms in patients for which celiac disease and wheat allergy have been ruled out. This article discusses these three conditions with their phatogenic mecanisms and the different clinic manifestations.

  6. Non-celiac gluten sensitivity and rheumatic diseases.

    PubMed

    Isasi, Carlos; Tejerina, Eva; Morán, Luz M

    2016-01-01

    Celiac disease is an autoimmune systemic disease having among its clinical manifestations frequent symptoms common to rheumatologic diseases such as musculoskeletal pain, asthenia, and cognitive fatigue. It is associated with other autoimmune diseases like Sjögren disease. It is a well-characterized disease with specific diagnostic tests. Non-celiac gluten sensitivity is an emerging entity with symptoms similar to celiac disease, but without specific diagnostic tests. The concept of non-celiac gluten sensitivity and its diagnostic problems are reviewed, and the hypothesis of its association with fibromyalgia, spondyloarthritis, and autoimmune conditions is proposed. Clinical observations supporting the hypothesis are described, highlighting the benefit of treating non-celiac gluten sensitivity.

  7. Non-celiac gluten sensitivity. Is it in the gluten or the grain?

    PubMed

    Nijeboer, Petula; Bontkes, Hetty J; Mulder, Chris J J; Bouma, Gerd

    2013-12-01

    Celiac disease is an immune-mediated inflammatory disorder of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals. Over the past several years, the concept of non-celiac gluten sensitivity (NCGS) has gained significant interest from the scientific community and mass media and the number of individuals embracing a gluten-free diet is rapidly growing. This condition is characterized by gastrointestinal or extraintestinal symptoms that respond to gluten withdrawal without evidence for underlying celiac disease or wheat allergy. Symptoms display significant overlap with the irritable bowel syndrome. Many important factors regarding this relatively novel condition remain to be elucidated; no discriminative markers to support a diagnosis of gluten sensitivity have been identified yet and its pathogenesis remains obscure. Here we review the current knowledge on NCGS, and outline potential pathogenic pathways of different gluten related disorders in order to gain clues about the pathophysiology of this novel condition.

  8. Celiac disease: understanding the gluten-free diet.

    PubMed

    Bascuñán, Karla A; Vespa, María Catalina; Araya, Magdalena

    2017-03-01

    The only effective and safe treatment of celiac disease (CD) continues being strict exclusion of gluten for life, the so-called gluten-free diet (GFD). Although this treatment is highly successful, following strict GFD poses difficulties to patients in family, social and working contexts, deteriorating his/her quality of life. We aimed to review main characteristics of GFD with special emphasis on factors that may interfere with adherence to it. We conducted a search of various databases, such as PubMed, Google Scholar, Embase, and Scielo, with focus on key words such as "gluten-free diet", "celiac disease", "gluten" and "gluten-free diet adherence". Available literature has not reached definitive conclusions on the exact amount of gluten that is harmless to celiac patients, although international agreements establish cutoff points for gluten-free products and advise the use of clinical assessment to tailor the diet according to individual needs. Following GFD must include eliminating gluten as ingredient as well as hidden component and potential cross contamination in foods. There are numerous grains to substitute wheat but composition of most gluten-free products tends to include only a small number of them, especially rice. The diet must be not only free of gluten but also healthy to avoid nutrient, vitamins and minerals deficiencies or excess. Overweight/obesity frequency has increased among celiac patients so weight gain deserves attention during follow up. Nutritional education by a trained nutritionist is of great relevance to achieve long-term satisfactory health status and good compliance. A balanced GFD should be based on a combination of naturally gluten-free foods and certified processed gluten-free products. How to measure and improve adherence to GFD is still controversial and deserves further study.

  9. Celiac disease treatment: gluten-free diet and beyond.

    PubMed

    Mäki, Markku

    2014-07-01

    The basis for celiac disease (CD) treatment is a strict lifelong gluten-free diet. On the diet, the small intestinal mucosal injury heals and gluten-induced symptoms and signs disappear. The mucosal healing is a prerequisite for sustaining health and is also obtained with a diet containing oats and trace amounts of gluten, industrially purified wheat starch-based gluten-free products. The small intestinal mucosa does not heal in noncompliant people, nor when a patient is inadvertently ingesting gluten. Development of adjunctive or alternative therapies is on its way. There are several novel treatment pipelines within academy and industry. Examples are the ideas of using glutenases as a drug to degrade the ingested gluten, polymers to bind and sequester the gluten to the feces, and also vaccine development for an immunotherapy to induce tolerance towards gluten. Clinical drug trials are to be foreseen in CD, soon also in children.

  10. Celiac Disease – Advances in Treatment via Gluten Modification

    PubMed Central

    Stoven, Samantha; Murray, Joseph A; Marietta, Eric

    2013-01-01

    Celiac Disease (CD) is an autoimmune enteropathy which occurs in genetically susceptible individuals carrying the prerequisite genetic markers HLA DQ2 or DQ8. These genetic markers are present in approximately 30% of the population, and the worldwide prevalence of CD is estimated to be approximately 1-2%. Currently a gluten-free diet is the only treatment for CD, but novel therapies aimed at gluten modification are underway. This review will discuss gluten based therapies including wheat alternatives and wheat selection, enzymatic alteration of wheat, oral enzyme supplements, and polymeric binders as exciting new therapies for treatment of Celiac Disease. PMID:22728383

  11. Non-celiac gluten sensitivity: Time for sifting the grain.

    PubMed

    Elli, Luca; Roncoroni, Leda; Bardella, Maria Teresa

    2015-07-21

    In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.

  12. Non-celiac gluten sensitivity: Time for sifting the grain

    PubMed Central

    Elli, Luca; Roncoroni, Leda; Bardella, Maria Teresa

    2015-01-01

    In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined. PMID:26217073

  13. Gluten-Related Disorders: Celiac Disease, Gluten Allergy, Non-Celiac Gluten Sensitivity.

    PubMed

    Allen, Patricia Jackson

    2015-01-01

    Gluten is a protein complex found in the endosperm portion of wheat, rye, and barley. "Gluten-related disorder" is a term used to describe conditions related to ingestion of gluten-containing foods. Gluten has been implicated as the cause of a variety of gastrointestinal (GI) and extraintestinal symptoms. These symptoms are often non-specific and variable, making it difficult for the primary care provider to diagnose the cause and develop a management plan. Recently, gluten-related disorders have received much attention in the popular press, and the sale of gluten-free foods has become a multi-billion dollar business. It is important for pediatric primary care providers to understand the potential role of gluten in GI health and symptomatology so appropriate screening, diagnostic testing, and management can be provided.

  14. [Non-celiac gluten sensitivity: Another condition that responds to gluten].

    PubMed

    Navarro, Elizabeth; Araya, Magdalena

    2015-05-01

    Remission of gastrointestinal and general symptoms after gluten withdrawal has been described in some non-celiac individuals for nearly 30 years. Only recently, efforts have been made to define this entity, now referred to as "non-celiac gluten sensitivity". It includes patients that clinically respond to gluten free diet without exhibiting allergic or autoimmune features to explain such response. Wheat allergy, celiac disease, irritable bowel syndrome and symptoms induced by high FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides And Polyols) consumption are the main differential diagnoses. The relationship with neuropsychiatric disorders such as schizophrenia and autism has not been demonstrated, but currently it gives ground to great hope in families with affected children. Epidemiology of non-celiac gluten sensitivity is not clear. It is described as more common among women and less common in children. Genetic and immune factors, changes in intestinal microbiota and non-gluten components present in wheat grains are main factors postulated in the pathogenesis of this condition. To date, there are no specific biomarkers for non-celiac gluten sensitivity and diagnosis is reached by excluding other causes of disease. A trial with gluten-free diet and subsequent gluten challenge is the methodology most frequently used to confirm diagnosis.

  15. Gluten and celiac disease--an immunological perspective.

    PubMed

    Rallabhandi, Prasad

    2012-01-01

    Gluten, a complex protein group in wheat, rye, and barley, causes celiac disease (CD), an autoimmune enteropathy of the small intestine, in genetically susceptible individuals. CD affects about 1% of the general population and causes significant health problems. Adverse inflammatory reactions to gluten are mediated by inappropriate T-cell activation leading to severe damage of the gastrointestinal mucosa, causing atrophy of absorptive surface villi. Gluten peptides bind to the chemokine receptor, CXCR3, and induce release of zonulin, which mediates tight-junction disassembly and subsequent increase in intestinal permeability. Proinflammatory cytokine IL-15 also contributes to the pathology of CD, by driving the expansion of intra-epithelial lymphocytes that damage the epithelium and promote the onset of T-cell lymphomas. There is no cure or treatment for CD, except for avoiding dietary gluten. Current gluten thresholds for food labeling have been established based on the available analytical methods, which show variation in gluten detection and quantification. Also, the clinical heterogeneity of celiac patients poses difficulty in defining clinically acceptable gluten thresholds in gluten-free foods. Presently, there is no bioassay available to measure gluten-induced immunobiological responses. This review focuses on various aspects of CD, and the importance of gluten thresholds and reference material from an immunological perspective.

  16. Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity.

    PubMed

    Jackson, Jessica R; Eaton, William W; Cascella, Nicola G; Fasano, Alessio; Kelly, Deanna L

    2012-03-01

    Celiac Disease (CD) is an immune-mediated disease dependent on gluten (a protein present in wheat, rye or barley) that occurs in about 1% of the population and is generally characterized by gastrointestinal complaints. More recently the understanding and knowledge of gluten sensitivity (GS), has emerged as an illness distinct from celiac disease with an estimated prevalence 6 times that of CD. Gluten sensitive people do not have villous atrophy or antibodies that are present in celiac disease, but rather they can test positive for antibodies to gliadin. Both CD and GS may present with a variety of neurologic and psychiatric co-morbidities, however, extraintestinal symptoms may be the prime presentation in those with GS. However, gluten sensitivity remains undertreated and underrecognized as a contributing factor to psychiatric and neurologic manifestations. This review focuses on neurologic and psychiatric manifestations implicated with gluten sensitivity, reviews the emergence of gluten sensitivity distinct from celiac disease, and summarizes the potential mechanisms related to this immune reaction.

  17. Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity

    PubMed Central

    Jackson, Jessica R.; Eaton, William W.; Cascella, Nicola G.; Fasano, Alessio

    2013-01-01

    Celiac Disease (CD) is an immune-mediated disease dependent on gluten (a protein present in wheat, rye or barley) that occurs in about 1% of the population and is generally characterized by gastrointestinal complaints. More recently the understanding and knowledge of gluten sensitivity (GS), has emerged as an illness distinct from celiac disease with an estimated prevalence 6 times that of CD. Gluten sensitive people do not have villous atrophy or antibodies that are present in celiac disease, but rather they can test positive for antibodies to gliadin. Both CD and GS may present with a variety of neurologic and psychiatric co-morbidities, however, extraintestinal symptoms may be the prime presentation in those with GS. However, gluten sensitivity remains undertreated and underrecognized as a contributing factor to psychiatric and neurologic manifestiations. This review focuses on neurologic and psychiatric manifestations implicated with gluten sensitivity, reviews the emergence of gluten sensitivity distinct from celiac disease, and summarizes the potential mechanisms related to this immune reaction. PMID:21877216

  18. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity.

    PubMed

    Caio, Giacomo; Volta, Umberto; Tovoli, Francesco; De Giorgio, Roberto

    2014-02-13

    Non-celiac gluten sensitivity is a syndrome characterized by gastrointestinal and extra-intestinal symptoms occurring in a few hours/days after gluten and/or other wheat protein ingestion and rapidly improving after exclusion of potential dietary triggers. There are no established laboratory markers for non-celiac gluten sensitivity, although a high prevalence of first generation anti-gliadin antibodies of IgG class has been reported in this condition. This study was designed to characterize the effect of the gluten-free diet on anti-gliadin antibodies of IgG class in patients with non-celiac gluten sensitivity. Anti-gliadin antibodies of both IgG and IgA classes were assayed by ELISA in 44 non-celiac gluten sensitivity and 40 celiac disease patients after 6 months of gluten-free diet. The majority of non-celiac gluten sensitivity patients (93.2%) showed the disappearance of anti-gliadin antibodies of IgG class after 6 months of gluten-free diet; in contrast, 16/40 (40%) of celiac patients displayed the persistence of these antibodies after gluten withdrawal. In non-celiac gluten sensitivity patients anti-gliadin antibodies IgG persistence after gluten withdrawal was significantly correlated with the low compliance to gluten-free diet and a mild clinical response. Anti-gliadin antibodies of the IgG class disappear in patients with non-celiac gluten sensitivity reflecting a strict compliance to the gluten-free diet and a good clinical response to gluten withdrawal.

  19. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity

    PubMed Central

    2014-01-01

    Background Non-celiac gluten sensitivity is a syndrome characterized by gastrointestinal and extra-intestinal symptoms occurring in a few hours/days after gluten and/or other wheat protein ingestion and rapidly improving after exclusion of potential dietary triggers. There are no established laboratory markers for non-celiac gluten sensitivity, although a high prevalence of first generation anti-gliadin antibodies of IgG class has been reported in this condition. This study was designed to characterize the effect of the gluten-free diet on anti-gliadin antibodies of IgG class in patients with non-celiac gluten sensitivity. Methods Anti-gliadin antibodies of both IgG and IgA classes were assayed by ELISA in 44 non-celiac gluten sensitivity and 40 celiac disease patients after 6 months of gluten-free diet. Results The majority of non-celiac gluten sensitivity patients (93.2%) showed the disappearance of anti-gliadin antibodies of IgG class after 6 months of gluten-free diet; in contrast, 16/40 (40%) of celiac patients displayed the persistence of these antibodies after gluten withdrawal. In non-celiac gluten sensitivity patients anti-gliadin antibodies IgG persistence after gluten withdrawal was significantly correlated with the low compliance to gluten-free diet and a mild clinical response. Conclusions Anti-gliadin antibodies of the IgG class disappear in patients with non-celiac gluten sensitivity reflecting a strict compliance to the gluten-free diet and a good clinical response to gluten withdrawal. PMID:24524388

  20. Noninflammatory Gluten Peptide Analogs as Biomarkers for Celiac Sprue

    PubMed Central

    Bethune, Michael T.; Crespo-Bosque, Mónica; Bergseng, Elin; Mazumdar, Kaushiki; Doyle, Lara; Sestak, Karol; Sollid, Ludvig M.; Khosla, Chaitan

    2013-01-01

    SUMMARY New tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for noninvasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized noninflammatory gluten peptide analogs in which key Gln residues are replaced by Asn or His. Like their proinflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2, or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice. PMID:19716477

  1. Mood disorders and non-celiac gluten sensitivity.

    PubMed

    Casella, Giovanni; Pozzi, Roberta; Cigognetti, Marta; Bachetti, Francesco; Torti, Gabriele; Cadei, Moris; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio

    2017-03-01

    The association between gluten related disorders and psychiatric diseases has been firmly demonstrated. Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients responsive to gluten-free diet after ruling out celiac disease and wheat allergy. The pathogenesis of neuro-psychiatric disorders in NCGS is unclear. An association between gluten and schizophrenia was described for the first time in 1950 by Bender et al. In the 1950's, Dicke noted that gluten-free diet improved mood in celiac patients. In 1970, Goldberg et al., in a study of 80 celiac patients, found that 34% of them showed minor affective disorders. Bipolar disorder patients show an increase of blood anti gliadin deamidated antibodies (IgG). The effect of diet and nutrition on autistic spectrum disorders has been investigated in the last two decades, particularly focusing on the symptoms of hyperactivity and attention. Toxoplasma gondii and other neurotropic pathogens as Influenzavirus and Coronavirus may be associated with mood disorders, probably secondary to an increased intestinal permeability. Abnormalities of host-microbiota interactions or of gut-microbiota composition have been associated with central nervous system disorders, such as autism, anxiety, depression and the integrity of intestinal microbiota may be considered a potential therapeutic goal to treat these conditions.

  2. Enzymatic Strategies to Detoxify Gluten: Implications for Celiac Disease

    PubMed Central

    Caputo, Ivana; Lepretti, Marilena; Martucciello, Stefania; Esposito, Carla

    2010-01-01

    Celiac disease is a permanent intolerance to the gliadin fraction of wheat gluten and to similar barley and rye proteins that occurs in genetically susceptible subjects. After ingestion, degraded gluten proteins reach the small intestine and trigger an inappropriate T cell-mediated immune response, which can result in intestinal mucosal inflammation and extraintestinal manifestations. To date, no pharmacological treatment is available to gluten-intolerant patients, and a strict, life-long gluten-free diet is the only safe and efficient treatment available. Inevitably, this may produce considerable psychological, emotional, and economic stress. Therefore, the scientific community is very interested in establishing alternative or adjunctive treatments. Attractive and novel forms of therapy include strategies to eliminate detrimental gluten peptides from the celiac diet so that the immunogenic effect of the gluten epitopes can be neutralized, as well as strategies to block the gluten-induced inflammatory response. In the present paper, we review recent developments in the use of enzymes as additives or as processing aids in the food biotechnology industry to detoxify gluten. PMID:21048862

  3. The broad spectrum of celiac disease and gluten sensitive enteropathy.

    PubMed

    Mocan, Oana; Dumitraşcu, Dan L

    2016-01-01

    The celiac disease is an immune chronic condition with genetic transmission, caused by the intolerance to gluten. Gluten is a protein from cereals containing the following soluble proteins: gliadine, which is the most toxic, and the prolamins. The average prevalence is about 1% in USA and Europe, but high in Africa: 5.6% in West Sahara. In the pathogenesis several factors are involved: gluten as external trigger, genetic predisposition (HLA, MYO9B), viral infections, abnormal immune reaction to gluten. Severity is correlated with the number of intraepithelial lymphocytes, cryptic hyperplasia and villous atrophy, as well as with the length of intestinal involvement. The severity is assessed according to the Marsh-Oberhuber staging. Diagnostic criteria are: positive serological tests, intestinal biopsy, the reversal after gluten free diet (GFD). Beside refractory forms, new conditions have been described, like the non celiac gluten intolerance. In a time when more and more people adhere to GFD for nonscientific reasons, practitioners should be updated with the progress in celiac disease knowledge.

  4. The broad spectrum of celiac disease and gluten sensitive enteropathy

    PubMed Central

    MOCAN, OANA; DUMITRAŞCU, DAN L.

    2016-01-01

    The celiac disease is an immune chronic condition with genetic transmission, caused by the intolerance to gluten. Gluten is a protein from cereals containing the following soluble proteins: gliadine, which is the most toxic, and the prolamins. The average prevalence is about 1% in USA and Europe, but high in Africa: 5.6% in West Sahara. In the pathogenesis several factors are involved: gluten as external trigger, genetic predisposition (HLA, MYO9B), viral infections, abnormal immune reaction to gluten. Severity is correlated with the number of intraepithelial lymphocytes, cryptic hyperplasia and villous atrophy, as well as with the length of intestinal involvement. The severity is assessed according to the Marsh–Oberhuber staging. Diagnostic criteria are: positive serological tests, intestinal biopsy, the reversal after gluten free diet (GFD). Beside refractory forms, new conditions have been described, like the non celiac gluten intolerance. In a time when more and more people adhere to GFD for nonscientific reasons, practitioners should be updated with the progress in celiac disease knowledge. PMID:27547052

  5. The opioid effects of gluten exorphins: asymptomatic celiac disease.

    PubMed

    Pruimboom, Leo; de Punder, Karin

    2015-11-24

    Gluten-containing cereals are a main food staple present in the daily human diet, including wheat, barley, and rye. Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could "mask" its own toxicity by exorphins that are produced through gluten protein digestion.

  6. Parallels between Pathogens and Gluten Peptides in Celiac Sprue

    PubMed Central

    Bethune, Michael T; Khosla, Chaitan

    2008-01-01

    Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights. PMID:18425213

  7. Physiopathology and Management of Gluten-Induced Celiac Disease.

    PubMed

    Kumar, Jitendra; Kumar, Manoj; Pandey, Rajesh; Chauhan, Nar Singh

    2017-02-01

    Proline- and glutamine-rich gluten proteins are one of the major constituents of cereal dietary proteins, which are largely resistant to complete cleavage by the human gastrointestinal (GI) digestive enzymes. Partial digestion of gluten generates approximately 35 amino acids (aa) immunomodulatory peptides which activate T-cell-mediated immune system, followed by immunological inflammation of mucosa leading to the onset of celiac disease (CD). CD is an autoimmune disease associated with HLA-DQ2/DQ8 polymorphism and dysbiosis of gut microbiota. CD is either diagnosed using duodenal mucosal biopsis or serological testing for transglutaminase 2 (TG2) specific antibodies (IgA and IgG). Current therapy for CD management is gluten-free diet, while other therapies like glutenase, probiotics, immunomodulation, jamming of HLA-DQ2, inhibition of TG2, and gluten tolerance aided by gluten tolerizing vaccines are being developed.

  8. [Treatment and prevention of gluten-sensitive celiac disease].

    PubMed

    Krums, L M; Parfenov, A I; Sabel'nikova, E A; Gudkova, R B; Vorob'eva, N N

    2011-01-01

    In this article presented results of examination and treatment of 207 patients with glutensensitive celiac disease. And also you can find comprehensive method for the treatment of patients with varying severity of disease. The fundamental method of therapy glutensensitive celiac disease is strict lifelong adherence to a gluten-free diet (GFD), which eliminated protein cereal--gluten contained in wheat, rye and barley. Recently, there is large number of products which include the "hidden gluten". Its elimination from the diet of GFD is mandatory for patients with celiac disease. In the presence of diarrhea and malabsorption syndrome are used adsorbents, astringents, enzymes, intestinal antiseptic, probiotics. With the purpose of correction of metabolic disorders intravenous electrolyte mixture containing potassium, calcium and magnesium. To eliminate protein deficiency drugs used solid protein mixture of pure amino acids, gluten-free mixes for enteral feeding. Clinical examination of patients with celiac disease is aimed at monitoring compliance with GFD, early detection of cancer, autoimmune and other related diseases.

  9. Diagnosis and classification of celiac disease and gluten sensitivity.

    PubMed

    Tonutti, Elio; Bizzaro, Nicola

    2014-01-01

    Celiac disease is a complex disorder, the development of which is controlled by a combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. New diagnostic guidelines developed by ESPGHAN emphasize the crucial role of serological tests in the diagnostic process of symptomatic subjects, and of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic subjects belonging to at-risk groups. The serological diagnosis of CD is based on the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti-deamidated gliadin peptide antibody assays of the IgG class are used. When anti-tTG antibody levels are very high, antibody specificity is absolute and CD can be diagnosed without performing a duodenum biopsy. Non-celiac gluten sensitivity is a gluten reaction in which both allergic and autoimmune mechanisms have been ruled out. Diagnostic criteria include the presence of symptoms similar to those of celiac or allergic patients; negative allergological tests and absence of anti-tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of the symptoms with a gluten-free diet; relapse of the symptoms when gluten is reintroduced.

  10. Osteoarticular manifestations of celiac disease and non-celiac gluten hypersensitivity.

    PubMed

    Dos Santos, Stéphanie; Lioté, Frédéric

    2017-05-01

    Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg. The diagnosis is confirmed by positive specific antibody, anti-transglutaminase or anti-endomysium, specific lesions of the small intestine and a response to strict gluten-free diet. The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia. In the absence of risk factor, osteoporosis, in a premenopausal women or in a man less than 55 years, more is if it is severe and refractory to medications, need to rheumatologists on the track of celiac disease in the absence of digestive symptoms. Osteomalacia is related to secondary hypovitaminosis D malabsorption. Supplementation by calcifediol, water-soluble vitamin D, may be indicated. Celiac disease is associated with an autoimmune disease in almost 1/3 of the cases. Knowing these potential associations allows earlier diagnosis in patients whose only manifestation, a concomitant disease. Anemia, chronic fatigue or unexplained polyarthralgia are symptoms associated with celiac disease to look for specific antibodies. The aim of early diagnosis is to prevent the emergence of other systemic disorders and avoid complications such as bone fractures and cancer, especially intestinal lymphoma. Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out, among patients without specific antibodies and without intestinal lesion of celiac disease. This entity is a cause, at

  11. World epidemiology of non-celiac gluten sensitivity.

    PubMed

    Vasagar, Brintha; Cox, Jessica; Herion, John T; Ivanoff, Erin

    2017-03-01

    While the term "gluten" has become commonplace, the disorders associated with gluten still remain poorly understood. Non-celiac gluten sensitivity (NCGS), the most recently recognized of the gluten-related disorders, is arguably the most unknown. While celiac disease and wheat allergy have diagnostic algorithm, NCGS remains a diagnosis of exclusion. With no evidence-based objective diagnostic criteria or serological tests, it is difficult to diagnose and even more difficult to study epidemiologically. Studies often use varied definitions of NCGS and are difficult to compare or validate. Further complicating diagnosis, NCGS has variable and wide-ranging symptoms which overlap with a number of other diseases and changes to diet are inherently difficult to study. In fact, some have argued that NCGS does not exist as a distinct entity or that it may not be caused by the gluten portion of foods. In this review, we outline the current knowledge, hypotheses, and debates surrounding the epidemiology of NCGS in the context of the spectrum of gluten-related disorders.

  12. The gluten connection: the association between schizophrenia and celiac disease.

    PubMed

    Kalaydjian, A E; Eaton, W; Cascella, N; Fasano, A

    2006-02-01

    Schizophrenia affects roughly 1% of the population and is considered one of the top 10 causes of disability worldwide. Given the immense cost to society, successful treatment options are imperative. Based on initial findings, gluten withdrawal may serve as a safe and economical alternative for the reduction of symptoms in a subset of patients. A review of the literature relevant to the association between schizophrenia and celiac disease (gluten intolerance) was conducted. A drastic reduction, if not full remission, of schizophrenic symptoms after initiation of gluten withdrawal has been noted in a variety of studies. However, this occurs only in a subset of schizophrenic patients. Large-scale epidemiological studies and clinical trials are needed to confirm the association between gluten and schizophrenia, and address the underlying mechanisms by which this association occurs.

  13. Animal models to study non-celiac gluten sensitivity.

    PubMed

    Amnuaycheewa, Plaimein; Murray, Joseph A; Marietta, Eric V

    2017-03-01

    Non-celiac gluten sensitivity (NCGS), sometimes known as non-celiac wheat sensitivity (NCWS), has recently received much attention, both scientific as well as from the alternative medical community. Over the past 5 years, there are over 200 publications on NCGS indexed on the PubMed database, the gluten-free market has been growing bigger, and it is clear that the number of consumers who are on a gluten-free diet (GFD) possibly because of a suspicion for NCGS appears to grow even faster. Nevertheless, despite these three rising events, many questions about NCGS remain unresolved. It is likely that NCGS represents a heterogeneous group of disorders linked by a common response to a GFD. It is still not fully understood how gluten, and likely other wheat proteins and components, could activate and drive the pathophysiology of NCGS. As a result, there are still no clear biomarkers, no robust clinical diagnostic criteria, nor a conclusive definition for NCGS. This heterogeneity can be approached by reducing the variables, in particular those of human behaviour and placebo effect, by studying animal models to address specific biological effects of wheat and/or gluten-related proteins. Herein we review the animal models and their potential to be used to advance our understanding of these disorders and potentially address their prevention and treatment.

  14. Celiac disease, gluten-free diet, and oats.

    PubMed

    Fric, Premysl; Gabrovska, Dana; Nevoral, Jiri

    2011-02-01

    Oats in a gluten-free diet increase the diet's nutritional value, but their use remains controversial. Contamination with prolamins of other cereals is frequent, and some clinical and experimental studies support the view that a subgroup of celiac patients may be intolerant to pure oats. Thus, this issue is more complex than previously suggested. In order to produce oats that are safe for all celiac patients, the following topics should be addressed: selection of oat cultivars with low avenin content, research on such recombinant varieties of oats, development of assay methods to detect avenins in oat products, guidelines for the agricultural processing of oats and the manufacture of oat products, as well as guidelines for following up with celiac patients who consume oats.

  15. Posttranslational modification of gluten shapes TCR usage in celiac disease.

    PubMed

    Qiao, Shuo-Wang; Ráki, Melinda; Gunnarsen, Kristin S; Løset, Geir-Åge; Lundin, Knut E A; Sandlie, Inger; Sollid, Ludvig M

    2011-09-15

    Posttranslational modification of Ag is implicated in several autoimmune diseases. In celiac disease, a cereal gluten-induced enteropathy with several autoimmune features, T cell recognition of the gluten Ag is heavily dependent on the posttranslational conversion of Gln to Glu residues. Evidence suggests that the enhanced recognition of deamidated gluten peptides results from improved peptide binding to the MHC and TCR interaction with the peptide-MHC complex. In this study, we report that there is a biased usage of TCR Vβ6.7 chain among TCRs reactive to the immunodominant DQ2-α-II gliadin epitope. We isolated Vβ6.7 and DQ2-αII tetramer-positive CD4(+) T cells from peripheral blood of gluten-challenged celiac patients and sequenced the TCRs of a large number of single T cells. TCR sequence analysis revealed in vivo clonal expansion, convergent recombination, semipublic response, and the notable conservation of a non-germline-encoded Arg residue in the CDR3β loop. Functional testing of a prototype DQ2-α-II-reactive TCR by analysis of TCR transfectants and soluble single-chain TCRs indicate that the deamidated residue in the DQ2-α-II peptide poses constraints on the TCR structure in which the conserved Arg residue is a critical element. The findings have implications for understanding T cell responses to posttranslationally modified Ags.

  16. Is gluten a cause of gastrointestinal symptoms in people without celiac disease?

    PubMed

    Biesiekierski, Jessica R; Muir, Jane G; Gibson, Peter R

    2013-12-01

    The avoidance of wheat- and gluten-containing products is a worldwide phenomenon. While celiac disease is a well-established entity, the evidence base for gluten as a trigger of symptoms in patients without celiac disease (so-called 'non-celiac gluten sensitivity' or NCGS) is limited. The problems lie in the complexity of wheat and the ability of its carbohydrate as well as protein components to trigger gastrointestinal symptoms, the potentially false assumption that response to a gluten-free diet equates to an effect of gluten withdrawal, and diagnostic criteria for coeliac disease. Recent randomized controlled re-challenge trials have suggested that gluten may worsen gastrointestinal symptoms, but failed to confirm patients with self-perceived NCGS have specific gluten sensitivity. Furthermore, mechanisms by which gluten triggers symptoms have yet to be identified. This review discusses the most recent scientific evidence and our current understanding of NCGS.

  17. Gluten-free diet and quality of life in celiac disease.

    PubMed

    Samasca, Gabriel; Sur, Genel; Lupan, Iulia; Deleanu, Diana

    2014-01-01

    Many recent studies overshadow the effects of gluten-free diet. Gluten-free diet positive effects were observed in celiac disease patients: increase in body mass index, higher energy intakes, reducing adiposity gain, moderates the risk of the associated complications. However, adhering to a gluten-free diet is difficult for many people. A new solution is needed for quality of life of celiac disease patients, not for celiac disease treatment. Health education on gluten-free diet at home and in society seems to be the solution. The aim of our study is to evaluate the recent research on gluten-free diet as a nutritional therapy for patients with celiac disease. To achieve this purpose we have analyzed the published studies from 2008 to the present on nutrition in celiac disease.

  18. Toxic, immunostimulatory and antagonist gluten peptides in celiac disease.

    PubMed

    Silano, Marco; Vincentini, Olimpia; De Vincenzi, Massimo

    2009-01-01

    Celiac disease (CD) is an increasingly diagnosed, permanent autoimmune enteropathy, triggered, in susceptible individuals, by the ingestion of gluten, the alcohol - soluble protein fraction of some cereals, such as wheat, rye and barley. The main protein of wheat gluten is called gliadin, the similar proteins of rye and barley are secalin and hordein, respectively. Approximately 96% of CD patients express the HLA molecule DQ2, while the remainder mostly express the less common haplotype DQ8, reflecting the pivotal role of these molecules in the pathogenesis of CD. Because of their aminoacid sequence and tri-dimensional structure, gluten peptides selectively bind to these HLA alleles present on the surface of antigen presenting cells and then they are presented to the T lymphocytes in intestinal mucosa, thus starting the inflammatory immune response. CD is defined by the characteristic histological changes of small bowel mucosa: villous atrophy, crypts hyperplasia and T cells infiltration of the lamina propria, along with the increase of the number of intra-epithelial lymphocytes. The withdrawal of the gluten- containing food from the diet determines a complete recovery of the intestinal mucosa, whereas the reintroduction causes a relapse of the disease. This review focuses on the description of gluten peptides that elicit the mucosal immune response via the activation of innate and adaptive immunity in CD. It also describes the antagonist gluten peptides, obtained by artificial modification of gluten T epitopes or naturally occurring in the alcohol protein fraction of a cultivar of durum wheat, able to immuno-modulate the pathogenic immune response of CD.

  19. Gluten ataxia is better classified as non-celiac gluten sensitivity than as celiac disease: a comparative clinical study.

    PubMed

    Rodrigo, Luis; Hernández-Lahoz, Carlos; Lauret, Eugenia; Rodriguez-Peláez, Maria; Soucek, Miroslav; Ciccocioppo, Rachele; Kruzliak, Peter

    2016-04-01

    Gluten ataxia (GA) has customarily been considered to be the main neurological manifestation of celiac disease (CD). In recent years, the condition of non-celiac gluten sensitivity (NCGS) has been defined, which includes some patients who are not considered "true celiacs." We performed a comparative clinicopathological study of these three entities. We studied 31 GA, 48 CD and 37 NCGS patients, prospectively in the same center for a period of 7 years. The protocol study included two serological determinations for gluten sensitivity [anti-gliadin IgA and IgG (AGA) and anti-tissue transglutaminase IgA (TG) antibodies], HLA-DQ2 typing, and duodenal histological assessment. Demographics and investigative findings were compared. Females were 55 % in GA, 75 % in CD (p < 0.001), and 47 % in NCGS (N.S.). GA patients were older (59 ± 14 years) than CD (43 ± 13 years) and NCGS (41 ± 8 years) groups (p < 0.001). AGA positivity was higher in GA (100 %) than in CD (48 %) groups (p < 0.001), but similar to NCGS patients (89 %; N.S.); TG positivity was lower in GA (3.2 %) than in CD (33.3 %; p < 0.001), but similar to NCGS (2.7 %; N.S.). DQ2 (+) was lower in GA (32.2 %) than in CD (89.6 %; p < 0.001), but similar to NCGS (29.7 %; N.S.). Lymphocytic enteritis (Marsh type 1) was lower in GA (9.6 %) than in CD (66.7 %; p < 0.001), but similar to NCGS (10.8 %; N.S.). The other gluten sensitivity-related characteristics measured were different to CD patients, but very close to NCGS. We conclude that GA patients are better classified within the NCGS group, than within CD.

  20. Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity.

    PubMed

    Brottveit, Margit; Beitnes, Ann-Christin R; Tollefsen, Stig; Bratlie, Jorunn E; Jahnsen, Frode L; Johansen, Finn-Eirik; Sollid, Ludvig M; Lundin, Knut E A

    2013-05-01

    In celiac disease (CD), gluten induces both adaptive and innate immune responses. Non-celiac gluten sensitivity (NCGS) is another form of gluten intolerance where the immune response is less characterized. The aim of our study was to explore and compare the early mucosal immunological events in CD and NCGS. We challenged 30 HLA-DQ2(+) NCGS and 15 CD patients, all on a gluten-free diet, with four slices of gluten-containing bread daily for 3 days. Duodenal biopsy specimens were collected before and after challenge. The specimens were examined for cytokine mRNA by quantitative reverse transcriptase-PCR and for MxA-expression and CD3(+) intraepithelial lymphocytes (IELs) by immunohistochemistry and compared with specimens from untreated CD patients and disease controls. In CD patients, tumor necrosis factor alpha (P=0.02) and interleukin 8 (P=0.002) mRNA increased after in vivo gluten challenge. The interferon gamma (IFN-γ) level of treated CD patients was high both before and after challenge and did not increase significantly (P=0.06). Four IFN-γ-related genes increased significantly. Treated and untreated CD patients had comparable levels of IFN-γ. Increased expression of MxA in treated CD patients after challenge suggested that IFN-α was activated on gluten challenge. In NCGS patients only IFN-γ increased significantly (P=0.03). mRNA for heat shock protein (Hsp) 27 or Hsp70 did not change in any of the groups. Importantly, we found that the density of IELs was higher in NCGS patients compared with disease controls, independent of challenge, although lower than the level for treated CD patients. CD patients mounted a concomitant innate and adaptive immune response to gluten challenge. NCGS patients had increased density of intraepithelial CD3(+) T cells before challenge compared with disease controls and increased IFN-γ mRNA after challenge. Our results warrant further search for the pathogenic mechanisms for NCGS.

  1. Celiac disease, non-celiac gluten sensitivity and inflammatory bowel disease.

    PubMed

    Casella, G; Di Bella, C; Salemme, M; Villanacci, V; Antonelli, E; Baldini, V; Bassotti, G

    2015-12-01

    Celiac disease (CD) and inflammatory bowel disease (IBD), such as Crohn's disease (CrD) and ulcerative colitis (UC), are chronic inflammatory condition of the gastro-intestinal tract. The prevalence of IBD in celiac patients has been reported as 5-10 times higher than in the general population. The possibility of the presence of CD in IBD should be considered in IBD patients with long-term iron deficiency anemia (IDA) not responsive to iron supplementation. Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra intestinal symptoms due to the ingestion of gluten-containing food in subject without CD and/or wheat allergy. Patients with Crohn's disease and SR-NCGS were more significantly affected by joint pains compared to UC patients (50% versus 11.1%). In Crohn's patients, a higher percentage of fatigue (50% versus 38.9%) and headache (27.3% versus 22.2%) was evident. For the association between NCGS and IBD new studies are warranted and, at this moment, a gluten free diet (GFD) may be useful more in CrD than in UC.

  2. Motility alterations in celiac disease and non-celiac gluten sensitivity.

    PubMed

    Pinto-Sanchez, Maria Ines; Bercik, Premysl; Verdu, Elena F

    2015-01-01

    Regulation of gut motility is complex and involves neuromuscular, immune and environmental mechanisms. It is well established that patients with celiac disease (CD) often display gut dysmotility. Studies have shown the presence of disturbed esophageal motility, altered gastric emptying, and dysmotility of the small intestine, gallbladder and colon in untreated CD. Most of these motor abnormalities resolve after a strict gluten-free diet, suggesting that mechanisms related to the inflammatory condition and disease process are responsible for the motor dysfunction. Motility abnormalities are also a hallmark of functional bowel disorders such as irritable bowel syndrome (IBS), where it has been proposed as underlying mechanism for symptom generation (diarrhea, constipation, bloating). Non-celiac gluten sensitivity (NCGS) is a poorly defined entity, mostly self-diagnosed, that presents clinically with IBS symptoms in the absence of specific celiac markers. Patients with NCGS are believed to react symptomatically to wheat components, and some studies have proposed the presence of low-grade inflammation in these patients. There is little information regarding the functional characterization of these patients before and after a gluten-free diet. A study suggested the presence of altered gastrointestinal transit in NCGS patients who also have a high prevalence of nonspecific anti-gliadin antibodies. Results of an ongoing clinical study in NCGS patients with positive anti-gliadin antibodies before and after a gluten-free diet will be discussed. Elucidating the mechanisms for symptom generation in NCGS patients is important to find new therapeutic alternatives to the burden of imposing a strict gluten-free diet in patients who do not have CD.

  3. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.

    PubMed

    Catassi, Carlo; Bai, Julio C; Bonaz, Bruno; Bouma, Gerd; Calabrò, Antonio; Carroccio, Antonio; Castillejo, Gemma; Ciacci, Carolina; Cristofori, Fernanda; Dolinsek, Jernej; Francavilla, Ruggiero; Elli, Luca; Green, Peter; Holtmeier, Wolfgang; Koehler, Peter; Koletzko, Sibylle; Meinhold, Christof; Sanders, David; Schumann, Michael; Schuppan, Detlef; Ullrich, Reiner; Vécsei, Andreas; Volta, Umberto; Zevallos, Victor; Sapone, Anna; Fasano, Alessio

    2013-09-26

    Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a "re-discovered" disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.

  4. Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

    PubMed Central

    Catassi, Carlo; Bai, Julio C.; Bonaz, Bruno; Bouma, Gerd; Calabrò, Antonio; Carroccio, Antonio; Castillejo, Gemma; Ciacci, Carolina; Cristofori, Fernanda; Dolinsek, Jernej; Francavilla, Ruggiero; Elli, Luca; Green, Peter; Holtmeier, Wolfgang; Koehler, Peter; Koletzko, Sibylle; Meinhold, Christof; Sanders, David; Schumann, Michael; Schuppan, Detlef; Ullrich, Reiner; Vécsei, Andreas; Volta, Umberto; Zevallos, Victor; Sapone, Anna; Fasano, Alessio

    2013-01-01

    Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS. PMID:24077239

  5. Immunogenetic Pathogenesis of Celiac Disease and Non-celiac Gluten Sensitivity.

    PubMed

    Escudero-Hernández, Celia; Peña, Amado Salvador; Bernardo, David

    2016-07-01

    Celiac disease is the most common oral intolerance in Western countries. It results from an immune response towards gluten proteins from certain cereals in genetically predisposed individuals (HLA-DQ2 and/or HLA-DQ8). Its pathogenesis involves the adaptive (HLA molecules, transglutaminase 2, dendritic cells, and CD4(+) T-cells) and the innate immunity with an IL-15-mediated response elicited in the intraepithelial compartment. At present, the only treatment is a permanent strict gluten-free diet (GFD). Multidisciplinary studies have provided a deeper insight of the genetic and immunological factors and their interaction with the microbiota in the pathogenesis of the disease. Similarly, a better understanding of the composition of the toxic gluten peptides has improved the ways to detect them in food and drinks and how to monitor GFD compliance via non-invasive approaches. This review, therefore, addresses the major findings obtained in the last few years including the re-discovery of non-celiac gluten sensitivity.

  6. Emerging therapeutic options for celiac disease: potential alternatives to a gluten-free diet.

    PubMed

    Bakshi, Anita; Stephen, Sindu; Borum, Marie L; Doman, David B

    2012-09-01

    Celiac disease is an autoimmune disorder of the small intestine that is more common than was previously thought. This disease is caused by an inappropriate immune response to wheat gluten, barley, and rye. Three main pathways cause celiac disease: the environmental trigger (gluten), genetic susceptibility, and unusual gut permeability. The only treatment currently available is a strict gluten-free diet. Unfortunately, a majority of patients have difficulty complying with this diet, and the response to therapy is poor. Therefore, alternative treatments are being developed, and new insights into the pathophysiology of celiac disease have led to research into novel therapies. New treatments include engineering gluten-free grains, decreasing intestinal permeability by blockage of the epithelial zonulin receptor, inducing oral tolerance to gluten with a therapeutic vaccine, and degrading immunodominant gliadin peptides using probiotics with endopeptidases or transglutaminase inhibitors. These nondiet-based therapies provide hope for enhanced, lifelong celiac disease management with improved patient compliance and better quality of life.

  7. Gluten sensitivity: problems of an emerging condition separate from celiac disease.

    PubMed

    Brown, Amy C

    2012-02-01

    Gluten sensitivity appears to be emerging as a separate condition from celiac disease, yet no clear definition or diagnosis exists. As a result, patients with gluten sensitivity experience delayed diagnosis and continuing symptoms if they consume gluten. This emerging medical problem may involve human genetics, plant genetic modifications, gluten as a food additive, environmental toxins, hormonal influences, intestinal infections and autoimmune diseases. The treatment is similar to that for celiac disease - a gluten-free diet. The use of a gluten-free diet or an elimination diet is encouraged in assisting people to determine whether or not they are gluten sensitive. It is time to not only recognize, but to treat and further research gluten sensitivity, as unconfirmed environmental factors continue to spread this problem further into the general population.

  8. Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad.

    PubMed

    Pietzak, Michelle

    2012-01-01

    As the gluten-free diet (GFD) gains in popularity with the general public, health practitioners are beginning to question its real health benefits. For those patients with celiac disease (CD), the GFD is considered medical nutrition therapy, as well as the only proven treatment that results in improvements in symptomatology and small bowel histology. Those with wheat allergy also benefit from the GFD, although these patients often do not need to restrict rye, barley, and oats from their diet. Gluten sensitivity is a controversial subject, where patients who have neither CD nor wheat allergy have varying degrees of symptomatic improvement on the GFD. Conditions in this category include dermatitis herpetiformis (DH), irritable bowel syndrome (IBS), and neurologic diseases such as gluten-sensitive ataxia and autism. It is important for patients and healthcare practitioners to understand the differences between these conditions, even though they may all respond to a GFD. Patients with CD can experience comorbid nutrition deficiencies and are at higher risk for the development of cancers and other autoimmune conditions. Those with wheat allergy and gluten sensitivity are thought not to be at higher risk for these complications. Defining the symptoms and biochemical markers for gluten-sensitive conditions is an important area for future investigations, and high-quality, large-scale randomized trials are needed to prove the true benefits of the GFD in this evolving field.

  9. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness.

    PubMed

    Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

    2013-09-01

    Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.

  10. Celiac Disease

    MedlinePlus

    ... without having celiac disease?Yes, you can have gluten sensitivity without the immune system attack on the small ... that gluten causes in celiac disease. Symptoms of gluten sensitivity are generally milder than those seen in celiac ...

  11. The Role of Gluten in Celiac Disease and Type 1 Diabetes

    PubMed Central

    Serena, Gloria; Camhi, Stephanie; Sturgeon, Craig; Yan, Shu; Fasano, Alessio

    2015-01-01

    Celiac disease (CD) and type 1 diabetes (T1D) are autoimmune conditions in which dietary gluten has been proven or suggested to play a pathogenic role. In CD; gluten is established as the instigator of autoimmunity; the autoimmune process is halted by removing gluten from the diet; which allows for resolution of celiac autoimmune enteropathy and subsequent normalization of serological markers of the disease. However; an analogous causative agent has not yet been identified for T1D. Nevertheless; the role of dietary gluten in development of T1D and the potentially beneficial effect of removing gluten from the diet of patients with T1D are still debated. In this review; we discuss the comorbid occurrence of CD and T1D and explore current evidences for the specific role of gluten in both conditions; specifically focusing on current evidence on the effect of gluten on the immune system and the gut microbiota. PMID:26343710

  12. The Role of Gluten in Celiac Disease and Type 1 Diabetes.

    PubMed

    Serena, Gloria; Camhi, Stephanie; Sturgeon, Craig; Yan, Shu; Fasano, Alessio

    2015-08-26

    Celiac disease (CD) and type 1 diabetes (T1D) are autoimmune conditions in which dietary gluten has been proven or suggested to play a pathogenic role. In CD; gluten is established as the instigator of autoimmunity; the autoimmune process is halted by removing gluten from the diet; which allows for resolution of celiac autoimmune enteropathy and subsequent normalization of serological markers of the disease. However; an analogous causative agent has not yet been identified for T1D. Nevertheless; the role of dietary gluten in development of T1D and the potentially beneficial effect of removing gluten from the diet of patients with T1D are still debated. In this review; we discuss the comorbid occurrence of CD and T1D and explore current evidences for the specific role of gluten in both conditions; specifically focusing on current evidence on the effect of gluten on the immune system and the gut microbiota.

  13. Age at Gluten Introduction and Risk of Celiac Disease

    PubMed Central

    Lee, Hye-Seung; Liu, Edwin; Uusitalo, Ulla; Hummel, Sandra; Yang, Jimin; Hummel, Michael; Rewers, Marian; She, Jin-Xiong; Simell, Olli; Toppari, Jorma; Ziegler, Anette-G.; Krischer, Jeffrey; Virtanen, Suvi M.; Norris, Jill M.; Agardh, Daniel

    2015-01-01

    OBJECTIVES: The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. METHODS: TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. RESULTS: Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7–8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47–2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34–2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. CONCLUSIONS: In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD. PMID:25601977

  14. Age at gluten introduction and risk of celiac disease.

    PubMed

    Aronsson, Carin Andrén; Lee, Hye-Seung; Liu, Edwin; Uusitalo, Ulla; Hummel, Sandra; Yang, Jimin; Hummel, Michael; Rewers, Marian; She, Jin-Xiong; Simell, Olli; Toppari, Jorma; Ziegler, Anette-G; Krischer, Jeffrey; Virtanen, Suvi M; Norris, Jill M; Agardh, Daniel

    2015-02-01

    The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD. Copyright © 2015 by the American Academy of Pediatrics.

  15. The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet.

    PubMed

    McAllister, Christopher S; Kagnoff, Martin F

    2012-07-01

    Celiac disease is a T cell-mediated autoimmune inflammatory disease of the small intestine that is activated by gluten. The diagnosis of celiac disease is challenging as patients display a wide range of symptoms and some are asymptomatic. A lifelong gluten-free diet is the only currently approved treatment of celiac disease. Although the diet is safe and effective, the compliance rates and patient acceptance vary. Furthermore, many patients treated with a gluten-free diet continue to be mildly to severely symptomatic with persistent histological abnormalities, and a small number of patients develop refractory celiac disease. New therapeutic adjuncts and potential alternatives to the gluten-free diet could improve the treatment options for these patients. Advances in understanding the immunopathogenesis of celiac disease have suggested several types of therapeutic strategies that may augment or supplant the gluten-free diet. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to celiac disease-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that reestablish mucosal homeostasis and tolerance to gluten antigens are also being explored. Additionally, it is vital to develop new therapeutic options for refractory celiac disease patients. This review highlights therapeutic strategies that may ultimately improve the health and well-being of individuals with celiac disease.

  16. Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

    PubMed Central

    Tack, Greetje J; van de Water, Jolanda MW; Bruins, Maaike J; Kooy-Winkelaar, Engelina MC; van Bergen, Jeroen; Bonnet, Petra; Vreugdenhil, Anita CE; Korponay-Szabo, Ilma; Edens, Luppo; von Blomberg, B Mary E; Schreurs, Marco WJ; Mulder, Chris J; Koning, Frits

    2013-01-01

    AIM: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients. METHODS: Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with adherence of the usual GFD, 14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline included complaints, quality-of-life, serum antibodies, immunophenotyping of T-cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life questionnaires were collected during and after the safety, washout and efficacy phase. Duodenal biopsies were collected after the safety phase and after the efficacy phase. A change in histological evaluation according to the modified Marsh classification was the primary endpoint. RESULTS: In total, 16 adults were enrolled in the study. No serious adverse events occurred during the trial and no patients withdrew during the trial. The mean score for the gastrointestinal subcategory of the celiac disease quality (CDQ) was relatively high throughout the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed. During the efficacy phase, neither the placebo nor the AN-PEP group developed significant antibody titers. The IgA-EM concentrations remained negative in both groups. Two patients were excluded from entering the efficacy phase as their

  17. Celiac Disease and Gluten-Free Oats: A Canadian Position Based on a Literature Review

    PubMed Central

    La Vieille, Sébastien; Pulido, Olga M.; Abbott, Michael; Koerner, Terence B.; Godefroy, Samuel

    2016-01-01

    This paper provides an overview of the latest scientific data related to the safety of uncontaminated oats (<20 ppm of gluten) in the diet of individuals with celiac disease (CD). It updates the previous Health Canada position posted on the Health Canada website in 2007 and a related paper published in 2009. It considers a number of recent studies published between January 2008 and January 2015. While recognizing that a few people with celiac disease seem to be clinically intolerant to oats, this review concludes that oats uncontaminated by gluten-containing cereals (wheat, rye, and barley) can be safely ingested by most patients with celiac disease and that there is no conclusive evidence that the consumption of uncontaminated or specially produced oats containing no greater than 20 ppm gluten by patients with celiac disease should be limited to a specific daily amount. However, individuals with CD should observe a stabilization phase before introducing uncontaminated oats to the gluten-free diet (GFD). Oats uncontaminated with gluten should only be introduced after all symptoms of celiac disease have resolved and the individual has been on a GFD for a minimum of 6 months. Long-term regular medical follow-up of these patients is recommended but this is no different recommendation to celiac individuals on a GFD without oats. PMID:27446825

  18. Celiac Disease and Gluten-Free Oats: A Canadian Position Based on a Literature Review.

    PubMed

    La Vieille, Sébastien; Pulido, Olga M; Abbott, Michael; Koerner, Terence B; Godefroy, Samuel

    2016-01-01

    This paper provides an overview of the latest scientific data related to the safety of uncontaminated oats (<20 ppm of gluten) in the diet of individuals with celiac disease (CD). It updates the previous Health Canada position posted on the Health Canada website in 2007 and a related paper published in 2009. It considers a number of recent studies published between January 2008 and January 2015. While recognizing that a few people with celiac disease seem to be clinically intolerant to oats, this review concludes that oats uncontaminated by gluten-containing cereals (wheat, rye, and barley) can be safely ingested by most patients with celiac disease and that there is no conclusive evidence that the consumption of uncontaminated or specially produced oats containing no greater than 20 ppm gluten by patients with celiac disease should be limited to a specific daily amount. However, individuals with CD should observe a stabilization phase before introducing uncontaminated oats to the gluten-free diet (GFD). Oats uncontaminated with gluten should only be introduced after all symptoms of celiac disease have resolved and the individual has been on a GFD for a minimum of 6 months. Long-term regular medical follow-up of these patients is recommended but this is no different recommendation to celiac individuals on a GFD without oats.

  19. [Intolerance of gluten--a new disease or undiagnosed celiac disease].

    PubMed

    Sabel'nikova, E A

    2012-01-01

    The prevalence of celiac disease is about 1% in the population and is growing due to the wide use of immunological methods of diagnosis. In recent years, in-depth research of the celiac disease has led not only to an increase in the number of patients with celiac disease, but also to the emergence of a broad spectrum of diseases associated with the ingestion of gluten. In this regard, a new pathology, known as "gluten intolerance or gluten sensitivity", attracted special attention of researchers. Studies in recent years have established that patients with this pathology may have both gastrointestinal symptoms and extraintestinal manifestations. Examinations of such patients usually do not find histological changes of the mucous membrane of the small intestine and autoimmune antibodies (to tissue transglutaminase (tTG) and endomysial (EMA)); however an increased level of gliadin antibodies (AGA) is often observed. Allergy to gluten is also absent. A gluten-free diet for such patients, like in case of the celiac disease, leads to the disappearance of clinical symptoms. Exact criteria for the diagnosis of this nosology have not been identified so far, but most researchers believe that prevalence of "gluten intolerance" is much higher than that of celiac disease.

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

    PubMed

    Makharia, Archita; Catassi, Carlo; Makharia, Govind K

    2015-12-10

    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.

  1. Oats can diversify a gluten-free diet in celiac disease and dermatitis herpetiformis.

    PubMed

    Peräaho, Markku; Collin, Pekka; Kaukinen, Katri; Kekkonen, Leila; Miettinen, Sanna; Mäki, Markku

    2004-07-01

    Finnish celiac disease and dermatitis herpetiformis patients have used oat-containing gluten-free diets since 1997. The aim of this study was to evaluate how the use of oats has been adopted. The use of oats and the effect of oats on symptoms and quality of life were investigated in 1,000 randomly selected members of the Celiac Society. Altogether, 710 patients responded: 423 (73%) with celiac disease and 70 (55%) with dermatitis herpetiformis were currently consuming oats. Patients appreciated the taste, the ease of use, and the low costs; 94% believed that oats diversified the gluten-free diet; 15% of celiac disease and 28% of dermatitis herpetiformis patients had stopped eating oats. The most common reasons for avoiding oats were fear of adverse effects or contamination. There is a market demand for oats, and celiac societies and dietitians should make efforts to promote the development of products free of wheat contamination.

  2. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness

    PubMed Central

    Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

    2013-01-01

    Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues. PMID:23934026

  3. Symptoms of Functional Intestinal Disorders Are Common in Patients with Celiac Disease Following Transition to a Gluten-Free Diet.

    PubMed

    Silvester, Jocelyn A; Graff, Lesley A; Rigaux, Lisa; Bernstein, Charles N; Leffler, Daniel A; Kelly, Ciarán P; Walker, John R; Duerksen, Donald R

    2017-07-07

    Celiac disease and functional intestinal disorders may overlap, yet the natural history of functional symptoms in patients with celiac disease is unknown. To investigate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and functional bloating (FB) symptoms among patients with celiac disease at diagnosis and during the first year of a gluten-free diet. Adults with a new diagnosis of celiac disease were surveyed at baseline, 6 months and 1 year using standardized measures for intestinal symptoms [Rome III diagnostic questionnaire and celiac symptom index (CSI)] and gluten-free diet adherence [gluten-free eating assessment tool (GF-EAT) and celiac diet adherence test]. At diagnosis, two-thirds fulfilled Rome III diagnostic questionnaire symptom criteria for IBS (52%), functional dyspepsia (27%), and/or functional bloating (9%). One year post-diagnosis, there was high adherence to a gluten-free diet as 93% reported gluten exposure less than once per month on the GF-EAT and only 8% had ongoing celiac disease symptoms (CSI score >45). The rates of those meeting IBS (22%) and functional dyspepsia (8%) symptom criteria both decreased significantly on a gluten-free diet. The prevalence of functional symptoms (any of IBS, FD or FB) at 1 year was 47%. Long-term follow-up of patients with celiac disease is necessary because many patients with celiac disease who are adherent to a gluten-free diet have persistent gastrointestinal symptoms.

  4. Small- bowel mucosal changes and antibody responses after low- and moderate-dose gluten challenge in celiac disease

    PubMed Central

    2011-01-01

    Background Due to the restrictive nature of a gluten-free diet, celiac patients are looking for alternative therapies. While drug-development programs include gluten challenges, knowledge regarding the duration of gluten challenge and gluten dosage is insufficient. We challenged adult celiac patients with gluten with a view to assessing the amount needed to cause some small-bowel mucosal deterioration. Methods Twenty-five celiac disease adults were challenged with low (1-3 g) or moderate (3-5g) doses of gluten daily for 12 weeks. Symptoms, small-bowel morphology, densities of CD3+ intraepithelial lymphocytes (IELs) and celiac serology were determined. Results Both moderate and low amounts of gluten induced small-bowel morphological damage in 67% of celiac patients. Moderate gluten doses also triggered mucosal inflammation and more gastrointestinal symptoms leading to premature withdrawals in seven cases. In 22% of those who developed significant small- intestinal damage, symptoms remained absent. Celiac antibodies seroconverted in 43% of the patients. Conclusions Low amounts of gluten can also cause significant mucosal deterioration in the majority of the patients. As there are always some celiac disease patients who will not respond within these conditions, sample sizes must be sufficiently large to attain to statistical power in analysis. PMID:22115041

  5. Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease.

    PubMed

    Hardy, Melinda Y; Girardin, Adam; Pizzey, Catherine; Cameron, Donald J; Watson, Katherine A; Picascia, Stefania; Auricchio, Renata; Greco, Luigi; Gianfrani, Carmen; La Gruta, Nicole L; Anderson, Robert P; Tye-Din, Jason A

    2015-11-01

    Developing antigen-specific approaches for diagnosis and treatment of celiac disease requires a detailed understanding of the specificity of T cells for gluten. The existing paradigm is that T-cell lines and clones from children differ from those of adults in the hierarchy and diversity of peptide recognition. We aimed to characterize the T-cell response to gluten in children vs adults with celiac disease. Forty-one children with biopsy-proven celiac disease (median age, 9 years old; 17 male), who had been on strict gluten-free diets for at least 3 months, were given a 3-day challenge with wheat; blood samples were collected and gluten-specific T cells were measured. We analyzed responses of T cells from these children and from 4 adults with celiac disease to a peptide library and measured T-cell receptor bias. We isolated T-cell clones that recognized dominant peptides and assessed whether gluten peptide recognition was similar between T-cell clones from children and adults. We detected gluten-specific responses by T cells from 30 of the children with celiac disease (73%). T cells from the children recognized the same peptides that were immunogenic to adults with celiac disease; deamidation of peptides increased these responses. Age and time since diagnosis did not affect the magnitude of T-cell responses to dominant peptides. T-cell clones specific for dominant α- or ω-gliadin peptides from children with celiac disease had comparable levels of reactivity to wheat, rye, and barley peptides as T-cell clones from adults with celiac disease. The α-gliadin-specific T cells from children had biases in T-cell receptor usage similar to those in adults. T cells from children with celiac disease recognize similar gluten peptides as T cells from adults with celiac disease. The findings indicate that peptide-based diagnostics and therapeutics for adults may also be used for children. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes.

    PubMed

    Ráki, Melinda; Dahal-Koirala, Shiva; Yu, Hao; Korponay-Szabó, Ilma R; Gyimesi, Judit; Castillejo, Gemma; Jahnsen, Jørgen; Qiao, Shuo-Wang; Sollid, Ludvig M

    2017-09-01

    Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults. We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection. Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes. T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. The gluten-free diet: a nutritional risk factor for adolescents with celiac disease?

    PubMed

    Mariani, P; Viti, M G; Montuori, M; La Vecchia, A; Cipolletta, E; Calvani, L; Bonamico, M

    1998-11-01

    The gluten-free diet is the standard therapy for patients affected by celiac disease, although compliance with the diet is not optimal in adolescents or adults. Moreover, the gluten-free diet may induce nutritional imbalances. Alimentary habits and diet composition were examined in 47 adolescents with celiac disease and 47 healthy aged-matched control subjects. All subjects compiled a 3-day alimentary record that allowed determination of their energy intakes: the macronutrient composition of their diets; and their iron, calcium, and fiber intakes. To evaluate compliance with the gluten-free diet, immunoglobulin A antigliadin and antiendomysium antibodies were assessed in all with celiac disease. The analysis of the records and the results of antibody levels showed that 25 subjects strictly followed dietetic prescriptions (group 1A), whereas 22 patients consumed gluten-containing food (group 1B). Those with celiac disease and control subjects (group 2) consumed a normocaloric diet. Lipid and protein consumption was high, however, and the consumption of carbohydrates low. Moreover, dietary levels of calcium, fiber, and especially in girls, iron, were low. These nutritional imbalances were significantly more evident in group 1A than in group 1B, as a consequence of poor alimentary choices. Moreover, in group 1A overweight and obesity were more frequent (72%) than in group 1B (51%) and in the control subjects (47%). In people with celiac disease, adherence to a strict gluten-free diet worsens the already nutritionally unbalanced diet of adolescents, increasing elevated protein and lipid consumption. In the follow-up of patients with celiac disease, considerable effort has yet to be made to improve compliance with a gluten-free diet, and especially to control the nutritional balance of the diet in compliant patients.

  8. Problems and challenges to adaptation of gluten free diet by Indian patients with celiac disease.

    PubMed

    Rajpoot, Preeti; Makharia, Govind K

    2013-11-27

    Celiac disease is emerging in India and has become a public health problem. Almost 6-8 million Indians are estimated to have celiac disease. While there is a large pool of patients with celiac disease in India, until now, only a fraction of them have been diagnosed. With increasing awareness about celiac disease amongst health care providers and the general population, a massive increase in the number of patients with celiac disease is expected now and in the subsequent decade in India. While the number of patients with celiac disease is increasing, the country's preparedness towards the emerging epidemic of this disease is minimal. There are a number of issues, which requires urgent attention. Some of the key issues include increased awareness amongst health care professionals and the general public about the disease and its management, team-based management of patients with celiac disease, proper counseling and supervision of patients, training of dietitians in the management of patients with celiac disease, industrial production of reliable and affordable gluten-free food, and food labeling for gluten contents.

  9. Problems and Challenges to Adaptation of Gluten Free Diet by Indian Patients with Celiac Disease

    PubMed Central

    Rajpoot, Preeti; Makharia, Govind K.

    2013-01-01

    Celiac disease is emerging in India and has become a public health problem. Almost 6–8 million Indians are estimated to have celiac disease. While there is a large pool of patients with celiac disease in India, until now, only a fraction of them have been diagnosed. With increasing awareness about celiac disease amongst health care providers and the general population, a massive increase in the number of patients with celiac disease is expected now and in the subsequent decade in India. While the number of patients with celiac disease is increasing, the country’s preparedness towards the emerging epidemic of this disease is minimal. There are a number of issues, which requires urgent attention. Some of the key issues include increased awareness amongst health care professionals and the general public about the disease and its management, team-based management of patients with celiac disease, proper counseling and supervision of patients, training of dietitians in the management of patients with celiac disease, industrial production of reliable and affordable gluten-free food, and food labeling for gluten contents. PMID:24288026

  10. Identification and in vitro reactivity of celiac immunoactive peptides in an apparent gluten-free beer.

    PubMed

    Real, Ana; Comino, Isabel; Moreno, Ma de Lourdes; López-Casado, Miguel Ángel; Lorite, Pedro; Torres, Ma Isabel; Cebolla, Ángel; Sousa, Carolina

    2014-01-01

    Gluten content from barley, rye, wheat and in certain oat varieties, must be avoid in individuals with celiac disease. In most of the Western countries, the level of gluten content in food to be considered as gluten-free products is below 20 parts per million measured by ELISA based on specific anti-gluten peptide antibody. However, in beverages or food suffering complex hydrolytic processes as beers, the relative proportion of reactive peptides for celiac patients and the analytical techniques may differ, because of the diversity of the resulting peptide populations after fermentations. A beer below 20 parts per million of gluten but yet detectable levels of gluten peptides by anti-gliadin 33-mer antibodies (G12 and A1) was analyzed. We identified and characterized the relevant peptides for either antibody recognition or immunoactivity in celiac patients. The beer was fractionated by HPLC. The relative reactivity of the different HPLC fractions to the G12/A1 antibodies correlated to the reactivity of peripheral blood mononuclear cells isolated from 14 celiac individuals. Peptides from representative fractions classified according to the relative reactivity to G12/A1 antibodies were identified by mass spectrometry. The beer peptides containing sequences with similarity to those of previously described G12 and A1 epitopes were synthesized and confirmed significant reactivity for the antibodies. The most reactive peptides for G12/A1 also confirmed the highest immunogenicity by peripheral blood mononuclear cell activation and interferon γ production from celiac patients. We concluded that preparative HPLC combined with anti-gliadin 33-mer G12/A1 antibodies were very sensitive and specific methods to analyze the relevant immunogenic peptides in hydrolyzed gluten.

  11. Identification and In Vitro Reactivity of Celiac Immunoactive Peptides in an Apparent Gluten-Free Beer

    PubMed Central

    Real, Ana; Comino, Isabel; Moreno, Mª de Lourdes; López-Casado, Miguel Ángel; Lorite, Pedro; Torres, Mª Isabel; Cebolla, Ángel; Sousa, Carolina

    2014-01-01

    Gluten content from barley, rye, wheat and in certain oat varieties, must be avoid in individuals with celiac disease. In most of the Western countries, the level of gluten content in food to be considered as gluten-free products is below 20 parts per million measured by ELISA based on specific anti-gluten peptide antibody. However, in beverages or food suffering complex hydrolytic processes as beers, the relative proportion of reactive peptides for celiac patients and the analytical techniques may differ, because of the diversity of the resulting peptide populations after fermentations. A beer below 20 parts per million of gluten but yet detectable levels of gluten peptides by anti-gliadin 33-mer antibodies (G12 and A1) was analyzed. We identified and characterized the relevant peptides for either antibody recognition or immunoactivity in celiac patients. The beer was fractionated by HPLC. The relative reactivity of the different HPLC fractions to the G12/A1 antibodies correlated to the reactivity of peripheral blood mononuclear cells isolated from 14 celiac individuals. Peptides from representative fractions classified according to the relative reactivity to G12/A1 antibodies were identified by mass spectrometry. The beer peptides containing sequences with similarity to those of previously described G12 and A1 epitopes were synthesized and confirmed significant reactivity for the antibodies. The most reactive peptides for G12/A1 also confirmed the highest immunogenicity by peripheral blood mononuclear cell activation and interferon γ production from celiac patients. We concluded that preparative HPLC combined with anti-gliadin 33-mer G12/A1 antibodies were very sensitive and specific methods to analyze the relevant immunogenic peptides in hydrolyzed gluten. PMID:24963630

  12. Cutting-edge issues in celiac disease and in gluten intolerance.

    PubMed

    Bizzaro, N; Tozzoli, R; Villalta, D; Fabris, M; Tonutti, E

    2012-06-01

    Celiac disease (CD) is a gluten-dependent immune-mediated disease with a prevalence in the general population estimated between 0.3% and 1.2%. Large-scale epidemiological studies have shown that only 10-20% of cases of CD are identified on the basis of clinical findings and that laboratory tests are crucial to identify subjects with subtle or atypical symptoms. The correct choice and clinical use of these diagnostic tools may enable accurate diagnosis and early recognition of silent CD cases. In this review, we have considered some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase-gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD.

  13. Repertoire of gluten peptides active in celiac disease patients: perspectives for translational therapeutic applications.

    PubMed

    Camarca, Alessandra; Del Mastro, Andrea; Gianfrani, Carmen

    2012-06-01

    Celiac disease is a common and lifelong food intolerance, affecting approximately 1% of the population. Because of a mechanism not completely understood, the ingestion of wheat gluten, and of homologue proteins of barley and rye, induces in genetically predisposed individuals pronounced inflammatory reactions mainly at the site of small intestine. Gluten, the triggering factor, is a complex protein mixture highly resistant to the gastrointestinal enzymatic proteolysis, and this results in the presence of large, and potentially immunogenic, peptides at the intestinal mucosa surface. During the last decade, several studies have defined gluten peptides able to stimulate adaptive T cells, of either CD4 or CD8 phenotype, and to activate innate (non T) immune cells. This review examines the complete repertoire of gluten peptides recognized by celiac T cells and discusses the several translational implications that the identification of these epitopes opens.

  14. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    PubMed Central

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

  15. Maize prolamins could induce a gluten-like cellular immune response in some celiac disease patients.

    PubMed

    Ortiz-Sánchez, Juan P; Cabrera-Chávez, Francisco; de la Barca, Ana M Calderón

    2013-10-21

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet.

  16. Microwave-based treatments of wheat kernels do not abolish gluten epitopes implicated in celiac disease.

    PubMed

    Gianfrani, Carmen; Mamone, Gianfranco; la Gatta, Barbara; Camarca, Alessandra; Di Stasio, Luigia; Maurano, Francesco; Picascia, Stefania; Capozzi, Vito; Perna, Giuseppe; Picariello, Gianluca; Di Luccia, Aldo

    2017-03-01

    Microwave based treatment (MWT) of wet wheat kernels induced a striking reduction of gluten, up to <20 ppm as determined by R5-antibodybased ELISA, so that wheat could be labeled as gluten-free. In contrast, analysis of gluten peptides by G12 antibody-based ELISA, mass spectrometry-based proteomics and in vitro assay with T cells of celiac subjects, indicated no difference of antigenicity before and after MWT. SDS-PAGE analysis and Raman spectroscopy demonstrated that MWT simply induced conformational modifications, reducing alcohol solubility of gliadins and altering the access of R5-antibody to the gluten epitopes. Thus, MWT neither destroys gluten nor modifies chemically the toxic epitopes, contradicting the preliminary claims that MWT of wheat kernels detoxifies gluten. This study provides evidence that R5-antibody ELISA alone is not effective to determine gluten in thermally treated wheat products. Gluten epitopes in processed wheat should be monitored using strategies based on combined immunoassays with T cells from celiacs, G12-antibody ELISA after proteolysis and proper molecular characterization.

  17. Gluten Introduction, Breastfeeding, and Celiac Disease: Back to the Drawing Board.

    PubMed

    Lebwohl, Benjamin; Murray, Joseph A; Verdú, Elena F; Crowe, Sheila E; Dennis, Melinda; Fasano, Alessio; Green, Peter H R; Guandalini, Stefano; Khosla, Chaitan

    2016-01-01

    This commentary by the leadership of the North American Society for the Study of Celiac Disease (NASSCD) concerns recent research findings regarding infant feeding practices. Celiac disease has increased markedly in recent decades, and seroprevalence studies indicate that this is a true rise, rather than one due to increased awareness and testing. Prior studies have suggested that infant feeding practices and timing of initial gluten exposure are central to the development of celiac disease. Two recent multicenter randomized trials tested strategies of early or delayed gluten introduction in infants, and neither strategy appeared to influence celiac disease risk. These studies also found that breastfeeding did not protect against the development of celiac disease. While disappointing, these results should spur the study of wider environmental risk factors beyond infant feeding, such as intrauterine and perinatal exposures as well as environmental influences later in life, including drug exposure, microbial infections, and the microbiome. Given that celiac disease can develop at any age, it is imperative to study these proposed triggers so as to elucidate the loss of tolerance to gluten and to develop future intervention strategies.

  18. [Non-celiac gluten sensitivity: a critical review of current evidence].

    PubMed

    Molina-Infante, Javier; Santolaria, Santos; Montoro, Miguel; Esteve, María; Fernández-Bañares, Fernando

    2014-01-01

    Non-celiac gluten sensitivity (NCGS) is an emerging disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food in non-celiac patients. Its prevalence has been estimated to be six to ten-times higher than that of celiac disease (CD). A gluten-free diet is the most widely recommended therapy, but the causative agent remains unknown and there are no consensus diagnostic criteria. Recent studies on NCGS have included patients with possibly overlooked minor CD and diarrhea-predominant irritable bowel syndrome without self-reported gluten intolerance, but showing a response to a gluten-free diet. Furthermore, FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) have recently been postulated as the culprit component for NCGS in wheat, instead of gluten. This review updates evidence on the pathophysiology of NCGS and the efficacy of different dietary interventions in its treatment, stressing the need for proper screening for CD before a diagnosis of NCGS is made.

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

    PubMed Central

    Makharia, Archita; Catassi, Carlo; Makharia, Govind K.

    2015-01-01

    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. PMID:26690475

  20. Effect of the timing of gluten introduction on the development of celiac disease.

    PubMed

    Silano, Marco; Agostoni, Carlo; Guandalini, Stefano

    2010-04-28

    Celiac disease (CD) is a permanent auto-immune enteropathy, triggered in genetically predisposed individuals by the ingestion of dietary gluten. Gluten is the alcohol-soluble protein component of the cereals wheat, rye and barley. CD is a multifactorial condition, originating from the interplay of genetic and environmental factors. The necessary environmental trigger is gluten, while the genetic predisposition has been identified in the major histocompatibility complex region on chromosome 6p21, with over 90% of CD patients expressing HLA DQ2 and the remaining celiac patients express DQ8. The fact that only about 4% of DQ2/8-positive individuals exposed to gluten develop CD, has led to the recognition that other genetic and environmental factors are also necessary. In the last few years, several epidemiological studies have suggested that the timing of the introduction of gluten, as well as the pattern of breastfeeding, may play an important role in the subsequent development of CD. Here, we present and review the most recent evidences regarding the effect of timing of gluten introduction during weaning, the amount of gluten introduced and simultaneous breastfeeding, on the development of CD.

  1. Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue.

    PubMed

    Gass, Jonathan; Bethune, Michael T; Siegel, Matthew; Spencer, Andrew; Khosla, Chaitan

    2007-08-01

    Celiac sprue is a multifactorial disease characterized by an inflammatory response to ingested gluten in the small intestine. Proteolytically resistant, proline- and glutamine-rich gluten peptides from wheat, rye, and barley persist in the intestinal lumen and elicit an immune response in genetically susceptible persons. We investigated a new combination enzyme product, consisting of a glutamine-specific endoprotease (EP-B2 from barley) and a prolyl endopeptidase (SC PEP from Sphingomonas capsulata), for its ability to digest gluten under gastric conditions. The ability of this combination enzyme to digest and detoxify whole-wheat bread gluten was investigated. In vitro and in vivo (rat) experimental systems were developed to simulate human gastric digestion, and the resulting material was analyzed by high-performance liquid chromatography, enzyme-linked immunoabsorbent assay, and patient-derived T-cell proliferation assays. The analysis revealed that EP-B2 extensively proteolyzes complex gluten proteins in bread, whereas SC PEP rapidly detoxifies the residual oligopeptide products of EP-B2 digestion. In vitro dose variation data suggests that an approximate 1:1 weight ratio of the 2 enzymes should maximize their synergistic potential. The efficacy of this 2-enzyme glutenase was verified in a rat model of gastric gluten digestion. By combining 2 enzymes with gastric activity and complementary substrate specificity, it should be possible to increase the safe threshold of ingested gluten, thereby ameliorating the burden of a highly restricted diet for patients with celiac sprue.

  2. The Cultivable Human Oral Gluten-Degrading Microbiome and its Potential Implications in Celiac Disease and Gluten Sensitivity

    PubMed Central

    Fernandez-Feo, Martin; Wei, Guoxian; Blumenkranz, Gabriel; Dewhirst, Floyd E.; Schuppan, Detlef; Oppenheim, Frank G.; Helmerhorst, Eva J.

    2013-01-01

    Celiac disease is characterized by intestinal inflammation caused by gluten, proteins which are widely contained in the Western diet. Mammalian digestive enzymes are only partly capable of cleaving gluten, and fragments remain that induce toxic responses in celiac patients. We found that the oral microbiome is a novel and rich source of gluten degrading enzymes. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on its immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterised by: 1) Hydrolysis of paranitroanilide-derivatised gliadin-derived tripeptide substrates; 2) Gliadin degradation in-gel (gliadin zymography); 3) Gliadin degradation in solution; 4) Proteolysis of the highly immunogenic α-gliadin-derived 33-mer. For select strains pH activity profiles were determined. The culturing strategy yielded 87 aerobic and 63 anaerobic strains. Species with activity in at least two of the four assays were typed as: Rothia mucilaginosa HOT-681, Rothia aeria HOT-188, Actinomyces odontolyticus HOT-701, Streptococcus mitis HOT-677, Streptococcus sp. HOT-071, Neisseria mucosa HOT-682 and Capnocytophaga sputigena HOT-775, with Rothia species being active in all four assays. Cleavage specificities and substrate preferences differed among the strains identified. The approximate molecular weights of the enzymes were ~75 kD (Rothia spp.), ~60 kD (A. odontolyticus) and ~150 kD (Streptococcus spp.). In conclusion, this study identified new gluten-degrading microorganisms in the upper gastro-intestinal tract. A cocktail of the most active oral bacteria, or their isolated enzymes, may offer promising new treatment modalities for celiac disease. PMID:23714165

  3. Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease

    PubMed Central

    Carrasco, Anna; Ibarra, Montserrat; Temiño, Rocío; Salas, Antonio; Esteve, Maria

    2016-01-01

    Background The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. Aim To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. Methods Double-blind randomized clinical trial of gluten vs placebo rechallenge. Inclusion criteria: >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated. Results 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable ‘coeliac lite’ disease. Conclusion This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet. Trial Registration ClinicalTrials.gov NCT02472704 PMID:27392045

  4. Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease.

    PubMed

    Rosinach, Mercè; Fernández-Bañares, Fernando; Carrasco, Anna; Ibarra, Montserrat; Temiño, Rocío; Salas, Antonio; Esteve, Maria

    2016-01-01

    The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. Double-blind randomized clinical trial of gluten vs placebo rechallenge. >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated. 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable 'coeliac lite' disease. This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet. ClinicalTrials.gov NCT02472704.

  5. The gluten-free diet: testing alternative cereals tolerated by celiac patients.

    PubMed

    Comino, Isabel; Moreno, María de Lourdes; Real, Ana; Rodríguez-Herrera, Alfonso; Barro, Francisco; Sousa, Carolina

    2013-10-23

    A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease, an autoimmune disorder of the small intestine associated with a permanent intolerance to gluten proteins. The complete elimination of gluten proteins contained in cereals from the diet is the key to celiac disease management. However, this generates numerous social and economic repercussions due to the ubiquity of gluten in foods. The research presented in this review focuses on the current status of alternative cereals and pseudocereals and their derivatives obtained by natural selection, breeding programs and transgenic or enzymatic technology, potential tolerated by celiac people. Finally, we describe several strategies for detoxification of dietary gluten. These included enzymatic cleavage of gliadin fragment by Prolyl endopeptidases (PEPs) from different organisms, degradation of toxic peptides by germinating cereal enzymes and transamidation of cereal flours. This information can be used to search for and develop cereals with the baking and nutritional qualities of toxic cereals, but which do not exacerbate this condition.

  6. The Gluten-Free Diet: Testing Alternative Cereals Tolerated by Celiac Patients

    PubMed Central

    Comino, Isabel; de Lourdes Moreno, María; Real, Ana; Rodríguez-Herrera, Alfonso; Barro, Francisco; Sousa, Carolina

    2013-01-01

    A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease, an autoimmune disorder of the small intestine associated with a permanent intolerance to gluten proteins. The complete elimination of gluten proteins contained in cereals from the diet is the key to celiac disease management. However, this generates numerous social and economic repercussions due to the ubiquity of gluten in foods. The research presented in this review focuses on the current status of alternative cereals and pseudocereals and their derivatives obtained by natural selection, breeding programs and transgenic or enzymatic technology, potential tolerated by celiac people. Finally, we describe several strategies for detoxification of dietary gluten. These included enzymatic cleavage of gliadin fragment by Prolyl endopeptidases (PEPs) from different organisms, degradation of toxic peptides by germinating cereal enzymes and transamidation of cereal flours. This information can be used to search for and develop cereals with the baking and nutritional qualities of toxic cereals, but which do not exacerbate this condition. PMID:24152755

  7. Aptamer binding to celiac disease-triggering hydrophobic proteins: a sensitive gluten detection approach.

    PubMed

    Amaya-González, Sonia; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Lobo-Castañón, M Jesús

    2014-03-04

    Celiac disease represents a significant public health problem in large parts of the world. A major hurdle in the effective management of the disease by celiac sufferers is the sensitivity of the current available methods for assessing gluten contents in food. In response, we report a highly sensitive approach for gluten analysis using aptamers as specific receptors. Gliadins, a fraction of gluten proteins, are the main constituent responsible for triggering the disease. However, they are highly hydrophobic and large molecules, regarded as difficult targets for in vitro evolution of aptamers without nucleobase modification. We describe the successful selection of aptamers for these water insoluble prolamins that was achieved choosing the immunodominant apolar peptide from α2-gliadin as a target for selection. All aptamers evolved are able to bind the target in its native environment within the natural protein. The best nonprotein receptor is the basis for an electrochemical competitive enzyme-linked assay on magnetic particles, which allows the measurement of as low as 0.5 ppb of gliadin standard (0.5 ppm of gluten). Reference immunoassay for detecting the same target has a limit of detection of 3 ppm, 6 times less sensitive than this method. Importantly, it also displays high specificity, detecting the other three prolamins toxic for celiac patients and not showing cross-reactivity to nontoxic proteins such as maize, soya, and rice. These features make the proposed method a valuable tool for gluten detection in foods.

  8. Treatment of celiac disease: from gluten-free diet to novel therapies.

    PubMed

    Francavilla, R; Cristofori, F; Stella, M; Borrelli, G; Naspi, G; Castellaneta, S

    2014-10-01

    Gluten-free diet (GFD) is the cornerstone treatment for celiac disease (CD). This diet excludes the protein gluten a protein forum in in grains such as wheat, barley, rye and triticale. Gluten causes small intestines inflammation in patients with CD and eating a GFD helps these patients in controlling signs and symptoms and prevent complications. Following a GFD may be frustrating, however, it is important to know that plenty of foods are naturally gluten-free and nowadays is relatively easy to find substitutes for gluten-containing foods. Certain grains, such as oats, are generally safe but can be contaminated with wheat during growing and processing stages of production. For this reason, it is generally recommended avoiding oats unless they are specifically labelled gluten-free. Other products that may contain gluten include food additives, such as malt flavouring, modified food starch and some supplement and/or vitamins that use gluten as a binding agent. Cross-contamination occurs when gluten-free foods come into contact with foods that contain gluten. It can happen during the manufacturing process or if the same equipment is used to make a variety of products. Cross-contamination can also occur at home if foods are prepared on common surfaces or with utensils that have not been cleaned after being used to prepare gluten-containing foods (using a toaster for gluten-free and regular bread). Although safe and effective, the GFD is not ideal: it is expensive, of limited nutritional value, and not readily available in many countries. Consequently, a need exists for novel, non-dietary therapies for celiac disease. Advances in understanding the immunopathogenesis of CD have suggested several types of therapeutic strategies alternative to the GFD. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during

  9. Delayed gastric emptying does not normalize after gluten withdrawal in adult celiac disease.

    PubMed

    Usai-Satta, Paolo; Oppia, Francesco; Scarpa, Mariella; Giannetti, Cristiana; Cabras, Francesco

    2016-08-01

    Objective Delayed gastric emptying has been frequently detected in patients with untreated celiac disease. According to several studies, gluten withdrawal showed to be effective in normalizing the gastric emptying rate. The aim of this study was to evaluate the gastric emptying rate of solids in patients with celiac disease before and after a gluten-free diet. Methods Twelve adult patients with celiac disease (age range 20-57 years) and 30 healthy controls (age range 30-54 years) underwent a (13)C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After at least 12 months of a gluten-free diet, celiac patients underwent a new (13)C-octanoic acid breath test. A symptom score was utilized to detect dyspeptic and malabsorption symptoms in all the patients. Results The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. On a gluten-free diet, surprisingly, the gastric emptying did not normalize despite an improvement of symptom score. No significant correlation between abnormal gastric emptying and specific symptom patterns, anthropometric parameters or severity of histological damage was found. Conclusions This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing gut hormone function. The persistence of these abnormalities on a gluten free diet suggests the presence of a persistent low-grade mucosal inflammation with a permanent perturbation of the neuro-immunomodulatory regulation.

  10. Salivary Gluten Degradation and Oral Microbial Profiles in Healthy Individuals and Celiac Disease Patients

    PubMed Central

    Tian, Na; Faller, Lina; Leffler, Daniel A.; Kelly, Ciaran P.; Hansen, Joshua; Bosch, Jos A.; Wei, Guoxian; Paster, Bruce J.; Schuppan, Detlef

    2017-01-01

    ABSTRACT Celiac disease (CD) is a chronic immune-mediated enteropathy induced by dietary gluten in genetically predisposed individuals. Saliva harbors the second highest bacterial load of the gastrointestinal (GI) tract after the colon. We hypothesized that enzymes produced by oral bacteria may be involved in gluten processing in the intestine and susceptibility to celiac disease. The aim of this study was to investigate salivary enzymatic activities and oral microbial profiles in healthy subjects versus patients with classical and refractory CD. Stimulated whole saliva was collected from patients with CD in remission (n = 21) and refractory CD (RCD; n = 8) and was compared to healthy controls (HC; n = 20) and subjects with functional GI complaints (n = 12). Salivary gluten-degrading activities were monitored with the tripeptide substrate Z-Tyr-Pro-Gln-pNA and the α-gliadin-derived immunogenic 33-mer peptide. The oral microbiome was profiled by 16S rRNA-based MiSeq analysis. Salivary glutenase activities were higher in CD patients compared to controls, both before and after normalization for protein concentration or bacterial load. The oral microbiomes of CD and RCD patients showed significant differences from that of healthy subjects, e.g., higher salivary levels of lactobacilli (P < 0.05), which may partly explain the observed higher gluten-degrading activities. While the pathophysiological link between the oral and gut microbiomes in CD needs further exploration, the presented data suggest that oral microbe-derived enzyme activities are elevated in subjects with CD, which may impact gluten processing and the presentation of immunogenic gluten epitopes to the immune system in the small intestine. IMPORTANCE Ingested gluten proteins are the triggers of intestinal inflammation in celiac disease (CD). Certain immunogenic gluten domains are resistant to intestinal proteases but can be hydrolyzed by oral microbial enzymes. Very little is known about the endogenous

  11. Salivary Gluten Degradation and Oral Microbial Profiles in Healthy Individuals and Celiac Disease Patients.

    PubMed

    Tian, Na; Faller, Lina; Leffler, Daniel A; Kelly, Ciaran P; Hansen, Joshua; Bosch, Jos A; Wei, Guoxian; Paster, Bruce J; Schuppan, Detlef; Helmerhorst, Eva J

    2017-03-15

    Celiac disease (CD) is a chronic immune-mediated enteropathy induced by dietary gluten in genetically predisposed individuals. Saliva harbors the second highest bacterial load of the gastrointestinal (GI) tract after the colon. We hypothesized that enzymes produced by oral bacteria may be involved in gluten processing in the intestine and susceptibility to celiac disease. The aim of this study was to investigate salivary enzymatic activities and oral microbial profiles in healthy subjects versus patients with classical and refractory CD. Stimulated whole saliva was collected from patients with CD in remission (n = 21) and refractory CD (RCD; n = 8) and was compared to healthy controls (HC; n = 20) and subjects with functional GI complaints (n = 12). Salivary gluten-degrading activities were monitored with the tripeptide substrate Z-Tyr-Pro-Gln-pNA and the α-gliadin-derived immunogenic 33-mer peptide. The oral microbiome was profiled by 16S rRNA-based MiSeq analysis. Salivary glutenase activities were higher in CD patients compared to controls, both before and after normalization for protein concentration or bacterial load. The oral microbiomes of CD and RCD patients showed significant differences from that of healthy subjects, e.g., higher salivary levels of lactobacilli (P < 0.05), which may partly explain the observed higher gluten-degrading activities. While the pathophysiological link between the oral and gut microbiomes in CD needs further exploration, the presented data suggest that oral microbe-derived enzyme activities are elevated in subjects with CD, which may impact gluten processing and the presentation of immunogenic gluten epitopes to the immune system in the small intestine.IMPORTANCE Ingested gluten proteins are the triggers of intestinal inflammation in celiac disease (CD). Certain immunogenic gluten domains are resistant to intestinal proteases but can be hydrolyzed by oral microbial enzymes. Very little is known about the endogenous proteolytic

  12. Gluten tolerance in adult patients with celiac disease 20 years after diagnosis?

    PubMed

    Hopman, Erica G D; von Blomberg, Mary E; Batstra, Manou R; Morreau, Hans; Dekker, Friedo W; Koning, Frits; Lamers, Cor B H W; Mearin, Maria Luisa

    2008-05-01

    Celiac disease (CD) is believed to be a permanent intolerance to gluten. A number of patients, however, discontinue the gluten-free diet (GFD) without developing symptoms or signs. The aim of our study was to investigate whether CD patients are capable of developing tolerance to gluten. All 77 adult patients from our hospital known to have biopsy-proven CD for more than 10 years were invited to participate. We investigated symptoms, gluten consumption, antibodies for CD and other autoimmunity, human leukocyte antigen (HLA)-typing, bone mineral density, and performed small bowel biopsies. Tolerance was defined as no immunological or histological signs of CD while consuming gluten. Sixty-six patients accepted participation, but after review of the diagnostic biopsies 53 were found to have true CD. Twenty-three percent of patients had a gluten-containing diet, 15% admitted gluten transgression and 62% followed the GFD. Patients on a GFD had significantly more osteoporosis. Normal small bowel mucosa was found in four of eight on gluten-containing diet and in four of four with gluten transgression. Two patients were considered to have developed tolerance to gluten. One of them was HLA-DQ2/DQ8 negative. Development of tolerance to gluten seems possible in some patients with CD. Further follow-up will show whether this tolerance is permanent or only a long-term return to latency. This feature may be associated with genetic characteristics, especially with HLA genotypes that differ from DQ2 or DQ8. More insight into the mechanisms of the development of gluten tolerance may help to distinguish those CD patients that might not require life-long GFD.

  13. Efficient chemo-enzymatic gluten detoxification: reducing toxic epitopes for celiac patients improving functional properties

    PubMed Central

    Ribeiro, Miguel; Nunes, Fernando M.; Guedes, Sofia; Domingues, Pedro; Silva, Amélia M.; Carrillo, Jose Maria; Rodriguez-Quijano, Marta; Branlard, Gérard; Igrejas, Gilberto

    2015-01-01

    Protein engineering of gluten, the exogenous effector in celiac disease, seeking its detoxification by selective chemical modification of toxic epitopes is a very attractive strategy and promising technology when compared to pharmacological treatment or genetic engineering of wheat. Here we present a simple and efficient chemo-enzymatic methodology that decreases celiac disease toxic epitopes of gluten proteins improving its technological value through microbial transglutaminase-mediated transamidation of glutamine with n-butylamine under reducing conditions. First, we found that using low concentrations of amine-nucleophile under non-reducing conditions, the decrease in toxic epitopes is mainly due to transglutaminase-mediated cross-linking. Second, using high amine nucleophile concentrations protein cross-linking is substantially reduced. Third, reducing conditions increase 7-fold the transamidation reaction further decreasing toxic epitopes amount. Fourth, using n-butylamine improves gluten hydrophobicity that strengthens the gluten network. These results open the possibility of tailoring gluten for producing hypoallergenic flours while still taking advantage of the unique viscoelastic properties of gluten. PMID:26691232

  14. Efficient chemo-enzymatic gluten detoxification: reducing toxic epitopes for celiac patients improving functional properties.

    PubMed

    Ribeiro, Miguel; Nunes, Fernando M; Guedes, Sofia; Domingues, Pedro; Silva, Amélia M; Carrillo, Jose Maria; Rodriguez-Quijano, Marta; Branlard, Gérard; Igrejas, Gilberto

    2015-12-22

    Protein engineering of gluten, the exogenous effector in celiac disease, seeking its detoxification by selective chemical modification of toxic epitopes is a very attractive strategy and promising technology when compared to pharmacological treatment or genetic engineering of wheat. Here we present a simple and efficient chemo-enzymatic methodology that decreases celiac disease toxic epitopes of gluten proteins improving its technological value through microbial transglutaminase-mediated transamidation of glutamine with n-butylamine under reducing conditions. First, we found that using low concentrations of amine-nucleophile under non-reducing conditions, the decrease in toxic epitopes is mainly due to transglutaminase-mediated cross-linking. Second, using high amine nucleophile concentrations protein cross-linking is substantially reduced. Third, reducing conditions increase 7-fold the transamidation reaction further decreasing toxic epitopes amount. Fourth, using n-butylamine improves gluten hydrophobicity that strengthens the gluten network. These results open the possibility of tailoring gluten for producing hypoallergenic flours while still taking advantage of the unique viscoelastic properties of gluten.

  15. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease.

    PubMed

    Stepniak, Dariusz; Spaenij-Dekking, Liesbeth; Mitea, Cristina; Moester, Martine; de Ru, Arnoud; Baak-Pablo, Renee; van Veelen, Peter; Edens, Luppo; Koning, Frits

    2006-10-01

    Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4-5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.

  16. Selective capture of most celiac immunogenic peptides from hydrolyzed gluten proteins.

    PubMed

    Moreno, María de Lourdes; Muñoz-Suano, Alba; López-Casado, Miguel Ángel; Torres, María Isabel; Sousa, Carolina; Cebolla, Ángel

    2016-08-15

    The available immunomethods for gluten quantitation could underestimate or overestimate the net immunoactivity of foods and beverages if the chosen analytical antibody is not specific to the relevant gluten immunogenic peptides (GIP). Accurate detection of the most active GIP is desirable to assess the potential celiac toxicity of food. We evaluated the capacity of the G12 monoclonal antibody for selectively depleting GIP in samples from two different gluteomes. Samples of hydrolyzed gliadin from wheat and a barley beer were used. The input (starting peptide digest of prolamins), the flow-through (unbound peptides), and the output (captured peptides) were analyzed by G12 and R5 competitive ELISA as well as by stimulation assays of T-cells from celiac patients. Most of the GIP were retained by the G12-agarose and represented the largest part of the immunogenicity of the gluten peptidome. G12 immunodepletion experiments with hydrolyzed gluten showed that this antibody reacted with those with the highest immunoactivity for celiac patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The relation between celiac disease, nonceliac gluten sensitivity and irritable bowel syndrome.

    PubMed

    El-Salhy, Magdy; Hatlebakk, Jan Gunnar; Gilja, Odd Helge; Hausken, Trygve

    2015-09-07

    Wheat products make a substantial contribution to the dietary intake of many people worldwide. Despite the many beneficial aspects of consuming wheat products, it is also responsible for several diseases such as celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS). CD and irritable bowel syndrome (IBS) patients have similar gastrointestinal symptoms, which can result in CD patients being misdiagnosed as having IBS. Therefore, CD should be excluded in IBS patients. A considerable proportion of CD patients suffer from IBS symptoms despite adherence to a gluten-free diet (GFD). The inflammation caused by gluten intake may not completely subside in some CD patients. It is not clear that gluten triggers the symptoms in NCGS, but there is compelling evidence that carbohydrates (fructans and galactans) in wheat does. It is likely that NCGS patients are a group of self-diagnosed IBS patients who self-treat by adhering to a GFD.

  18. Change in lipid profile in celiac disease: beneficial effect of gluten-free diet.

    PubMed

    Brar, Pardeep; Kwon, Grace Y; Holleran, Steve; Bai, Diane; Tall, Alan R; Ramakrishnan, Rajasekhar; Green, Peter H R

    2006-09-01

    Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults. We therefore examined the effect of a gluten-free diet on the lipid profile in patients with celiac disease. We identified 132 patients with celiac disease who adhered to a gluten-free diet and had lipid profiles performed before and after a median of 20.5 months on the diet. The patients lacked diseases that may affect serum lipids. There were significant increases in total cholesterol and high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density lipoprotein (LDL) cholesterol (P=.06). The LDL/HDL ratio decreased by 0.36+/-0.7 (P < .0001). Both men and women had a significant increase in total cholesterol and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases in LDL (P=.02). The greatest increase in lipid values was seen in those with the lowest initial values. The largest increase in HDL was seen in subjects with more severe disease as indicated by low albumin level and presence of total villous atrophy. Diagnosis of celiac disease and its treatment with a gluten-free diet resulted in improvement in the lipoprotein profile, which included an increase in HDL and a decrease in the LDL/HDL ratio.

  19. Evaluation of gluten in gluten-free-labeled foods and assessment of exposure level to gluten among celiac patients in Lebanon.

    PubMed

    Hassan, Hussein; Elaridi, Jomana; Bassil, Maya

    2017-03-21

    The aim of the study was to evaluate gluten contamination in all the gluten-free (GF)-labeled food products sold in Lebanon. Over a 2-year period, a total of 173 food samples collected from 135 brand names were analyzed. Gluten contamination was detected in 33 of 173 (19%) samples, and its content ranged between 2.5 and >80 mg kg(-1). In 10 of the 173 samples (6%), the quantity of gluten exceeded the upper limit of 20 mg kg(-1). Out of the 10 contaminated products, eight (80%) were locally manufactured. Among these 10 products, eight (80%) were wheat-starch-based foods. Of the 40 brand names tested twice in 2014 and 2015, 15 (38%) showed significantly (p < .05) different gluten content between the 2 years. Using a food frequency questionnaire, exposure level to gluten through the contaminated products was evaluated among 15 celiac patients. Two patients reported consuming these products more than twice per week.

  20. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.

    PubMed

    Biesiekierski, Jessica R; Peters, Simone L; Newnham, Evan D; Rosella, Ourania; Muir, Jane G; Gibson, Peter R

    2013-08-01

    Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS. We performed a double-blind cross-over trial of 37 subjects (aged 24-61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales. In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day rechallenge, participants' symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed. In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Celiac Disease and Gluten-Free Diet Videos

    MedlinePlus

    ... Medical Center in Washington D.C., Dr. Gary Kaplan, Medical Director of Kaplan Center for Integrative Medicine and Cheryl Harris, MPH, ... Snyder: Testing and Diagnosis (Part 3) Dr. Gary Kaplan: Gluten Sensitivity Cheryl Harris, MPH, RD: What is ...

  2. Pathophysiology of non-celiac gluten sensitivity: where are we now?

    PubMed

    Caio, Giacomo; Riegler, Gabriele; Patturelli, Marta; Facchiano, Angela; DE Magistris, Laura; Sapone, Anna

    2017-03-01

    Non-celiac gluten sensitivity (NCGS) is the term used to describe individuals complaining of intestinal and extra-intestinal symptoms related to gluten ingestion and rapidly improving after its withdrawal, and in which both celiac disease (CD) and wheat allergy (WA) were properly ruled out. The prevalence of this condition remains unknown and a lot of questions about the possible pathogenetic mechanisms are still unclarified. It is believed that NCGS represents a heterogeneous condition with different subgroups potentially characterized by different pathogenesis, clinical history, and clinical course. Moreover, a possible overlap with irritable bowel syndrome (IBS) and other functional diseases could complicate patient selection for clinical studies, slowing down the understanding of this disorder. Last but not least, the lack of validated biomarkers remains a significant limitation in research studies on NCGS. Hence, there is a need for strict diagnostic criteria for NCGS.

  3. Mutatis mutandis: are we diagnosing too many people with non-celiac gluten sensitivity? Multiple case report.

    PubMed

    Borghini, Raffaele; Donato, Giuseppe; Di Tola, Marco; Isonne, Claudia; Picarelli, Antonio

    2014-06-01

    We report three patients presenting with gluten-related signs and symptoms. Since villous height/crypt depth ratio, intraepithelial lymphocyte count, and serum antibody tests were not diagnostic for celiac disease (CD), a diagnosis of non-celiac gluten sensitivity (NCGS) was suggested. On the other hand, antibodies suggestive for CD surprisingly showed positive results in the duodenal biopsy organ culture of all three cases. The reported cases suggest the precious potential role that organ culture systems may play in differentiating CD from NCGS. This method should be recommended when gluten-related disorders are suspected in order to reduce the inappropriate diagnosis of NCGS.

  4. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria

    PubMed Central

    Catassi, Carlo; Elli, Luca; Bonaz, Bruno; Bouma, Gerd; Carroccio, Antonio; Castillejo, Gemma; Cellier, Christophe; Cristofori, Fernanda; de Magistris, Laura; Dolinsek, Jernej; Dieterich, Walburga; Francavilla, Ruggiero; Hadjivassiliou, Marios; Holtmeier, Wolfgang; Körner, Ute; Leffler, Dan A.; Lundin, Knut E. A.; Mazzarella, Giuseppe; Mulder, Chris J.; Pellegrini, Nicoletta; Rostami, Kamran; Sanders, David; Skodje, Gry Irene; Schuppan, Detlef; Ullrich, Reiner; Volta, Umberto; Williams, Marianne; Zevallos, Victor F.; Zopf, Yurdagül; Fasano, Alessio

    2015-01-01

    Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally. PMID:26096570

  5. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria.

    PubMed

    Catassi, Carlo; Elli, Luca; Bonaz, Bruno; Bouma, Gerd; Carroccio, Antonio; Castillejo, Gemma; Cellier, Christophe; Cristofori, Fernanda; de Magistris, Laura; Dolinsek, Jernej; Dieterich, Walburga; Francavilla, Ruggiero; Hadjivassiliou, Marios; Holtmeier, Wolfgang; Körner, Ute; Leffler, Dan A; Lundin, Knut E A; Mazzarella, Giuseppe; Mulder, Chris J; Pellegrini, Nicoletta; Rostami, Kamran; Sanders, David; Skodje, Gry Irene; Schuppan, Detlef; Ullrich, Reiner; Volta, Umberto; Williams, Marianne; Zevallos, Victor F; Zopf, Yurdagül; Fasano, Alessio

    2015-06-18

    Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts' recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

  6. Gluten-degrading bacteria are present in the human small intestine of healthy volunteers and celiac patients.

    PubMed

    Herrán, Alexandra R; Pérez-Andrés, Jénifer; Caminero, Alberto; Nistal, Esther; Vivas, Santiago; Ruiz de Morales, José María; Casqueiro, Javier

    2017-09-01

    Gluten is the only known environmental factor that triggers celiac disease. Several studies have described an imbalance between the intestinal microbiota of different individuals based on diagnoses. Moreover, recent studies have suggested that human bacteria may play an important role in gluten hydrolysis. However, there has been no research focusing on the small intestine. This study aimed to characterize the adult small intestine microbiota possibly implicated in gluten hydrolysis. Duodenal biopsies from different diagnosed individuals were cultured in a gluten-containing medium, and the grown microbiota was analyzed by culture dependent/independent methods. Results showed that gluten-degrading bacteria can be found in the human small intestine. Indeed, 114 bacterial strains belonging to 32 species were isolated; 85 strains were able to grow in a medium containing gluten as the sole nitrogen source, 31 strains showed extracellular proteolytic activity against gluten protein and 27 strains showed peptidolytic activity towards the 33 mer peptide, an immunogenic peptide for celiac disease patients. We found that there are no differences based on the diagnosis, but each individual has its own population of gluten-hydrolyzing bacteria. These bacteria or their gluten-degrading enzymes could help to improve the quality of life of celiac disease patients'. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  7. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease.

    PubMed

    Tye-Din, Jason A; Stewart, Jessica A; Dromey, James A; Beissbarth, Tim; van Heel, David A; Tatham, Arthur; Henderson, Kate; Mannering, Stuart I; Gianfrani, Carmen; Jewell, Derek P; Hill, Adrian V S; McCluskey, James; Rossjohn, Jamie; Anderson, Robert P

    2010-07-21

    Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible.

  8. Non-celiac gluten sensitivity: clinical relevance and recommendations for future research.

    PubMed

    Mooney, P D; Aziz, I; Sanders, D S

    2013-11-01

    There has been increasing interest in the entity of Non-Celiac Gluten Sensitivity (NCGS) in recent years; however, it still remains a controversial topic and its pathogenesis is not well understood. Celiac Disease, in contrast, is a well-studied condition that has become increasingly recognized as a prevalent condition arising from a heightened immunological response to gluten. Wheat allergy is an IgE-mediated condition capable of causing a variety of gastrointestinal symptoms. However, the number of patients who have neither celiac disease nor wheat allergy, but appear to derive benefit from a gluten-free diet, is also increasing substantially. The use of the term NCGS as a way of describing this condition has become increasingly prevalent in recent years. In this review, we will focus on gastrointestinal manifestations of NCGS and discuss the evidence for the condition and its putative pathogenesis. We will discuss areas of controversy and areas for potential future research. © 2013 John Wiley & Sons Ltd.

  9. Serum I-FABP Detects Gluten Responsiveness in Adult Celiac Disease Patients on a Short-Term Gluten Challenge.

    PubMed

    Adriaanse, Marlou P M; Leffler, Daniel A; Kelly, Ciaran P; Schuppan, Detlef; Najarian, Robert M; Goldsmith, Jeffrey D; Buurman, Wim A; Vreugdenhil, Anita C E

    2016-07-01

    Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD. Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous-height to crypt-depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects. Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r=0.458, P=0.042) and at day 14 (r=0.654, P=0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC. Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings.

  10. Does gluten intake influence the development of celiac disease-associated complications?

    PubMed

    Elli, Luca; Discepolo, Valentina; Bardella, Maria T; Guandalini, Stefano

    2014-01-01

    Celiac disease (CD) is regarded as the most common autoimmune enteropathy in western countries. Epidemiological studies indicate that approximately 1:100 individuals may present with histologically proven CD. CD develops in genetically predisposed subjects after gluten ingestion. It usually subsides after gluten is withdrawn from their diet. Gluten is the only known environmental factor that affects the progression/regression of the intestinal villous atrophy, which is the hallmark of this disease. CD generally follows a benign course after gluten elimination. However, it is also associated with the development of other autoimmune disorders or of intestinal malignancies. The issue of whether such complications, sometimes of significant clinical and prognostic impact, are or are not the result of ongoing gluten ingestion, is an important one that has been investigated over the recent years with conflicting results. In terms of practical implications, the presence of a positive correlation between gluten intake and the development of severe complications would lead to the need for early diagnosis and mass screening. The lack of such correlation would instead suggest a less aggressive diagnostic strategy. This review aims at critically summarizing the evidence supporting either hypothesis.

  11. Autoimmune diseases and celiac disease which came first: genotype or gluten?

    PubMed

    Diamanti, Antonella; Capriati, Teresa; Bizzarri, Carla; Ferretti, Francesca; Ancinelli, Monica; Romano, Francesca; Perilli, Alessia; Laureti, Francesca; Locatelli, Mattia

    2016-01-01

    Celiac disease (CD) is associated with several autoimmune diseases (ADs) and, in particular, thyroid autoimmunity (TA) and Type 1 diabetes (T1D). TA and T1D are defined as 'associated conditions' to CD (conditions at increased prevalence in CD but not directly related to gluten ingestion). The diagnosis of CD may precede or follow that of TA/T1D. To date, the available evidence suggests that the common genetic background is the main factor determining the high prevalence of the association. Conversely, no conclusive findings clarify whether extrinsic gluten-related factors (age at the first introduction, concomitant breastfeeding, length of gluten exposure and gluten-free diet) may link CD to the ADs. The aim of this review is to evaluate whether genetic background alone could explain the association between CD and ADs or if gluten-related factors ought to be considered. The pathophysiological links clarifying how the gluten-related factors could predispose to ADs will also be discussed.

  12. Magneto immunosensor for gliadin detection in gluten-free foodstuff: towards food safety for celiac patients.

    PubMed

    Laube, T; Kergaravat, S V; Fabiano, S N; Hernández, S R; Alegret, S; Pividori, M I

    2011-09-15

    Gliadin is a constituent of the cereal protein gluten, responsible for the intolerance generated in celiac disease. Its detection is of high interest for food safety of celiac patients, since the only treatment known until now is a lifelong avoidance of this protein in the diet. Therefore, it is essential to have an easy and reliable method of analysis to control the contents in gluten-free foods. An electrochemical magneto immunosensor for the quantification of gliadin or small gliadin fragments in natural or pretreated food samples is described for the first time and compared to a novel magneto-ELISA system based on optical detection. The immunological reaction was performed on magnetic beads as solid support by the oriented covalent immobilization, of the protein gliadin on tosyl-activated beads. Direct, as well as indirect competitive immunoassays were optimized, achieving the best analytical performance with the direct competitive format. Excellent detection limits (in the order of μg L(-1)) were achieved, according to the legislation for gluten-free products. The matrix effect, as well as the performance of the assays was successfully evaluated using spiked gluten-free foodstuffs (skimmed milk and beer), obtaining excellent recovery values in the results.

  13. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

    PubMed

    Biesiekierski, Jessica R; Newnham, Evan D; Irving, Peter M; Barrett, Jacqueline S; Haines, Melissa; Doecke, James D; Shepherd, Susan J; Muir, Jane G; Gibson, Peter R

    2011-03-01

    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.

  14. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance.

    PubMed

    Samsel, Anthony; Seneff, Stephanie

    2013-12-01

    Celiac disease, and, more generally, gluten intolerance, is a growing problem worldwide, but especially in North America and Europe, where an estimated 5% of the population now suffers from it. Symptoms include nausea, diarrhea, skin rashes, macrocytic anemia and depression. It is a multifactorial disease associated with numerous nutritional deficiencies as well as reproductive issues and increased risk to thyroid disease, kidney failure and cancer. Here, we propose that glyphosate, the active ingredient in the herbicide, Roundup(®), is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate's strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate's known depletion of these amino acids. Celiac disease patients have an increased risk to non-Hodgkin's lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with celiac disease, such as infertility, miscarriages, and birth defects, can also be explained by glyphosate. Glyphosate residues in wheat and other crops are likely increasing recently due to the growing practice of crop desiccation just prior to the harvest. We argue that the practice of "ripening" sugar cane with glyphosate may explain the recent

  15. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance

    PubMed Central

    Samsel, Anthony

    2013-01-01

    Celiac disease, and, more generally, gluten intolerance, is a growing problem worldwide, but especially in North America and Europe, where an estimated 5% of the population now suffers from it. Symptoms include nausea, diarrhea, skin rashes, macrocytic anemia and depression. It is a multifactorial disease associated with numerous nutritional deficiencies as well as reproductive issues and increased risk to thyroid disease, kidney failure and cancer. Here, we propose that glyphosate, the active ingredient in the herbicide, Roundup®, is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate's strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate's known depletion of these amino acids. Celiac disease patients have an increased risk to non-Hodgkin's lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with celiac disease, such as infertility, miscarriages, and birth defects, can also be explained by glyphosate. Glyphosate residues in wheat and other crops are likely increasing recently due to the growing practice of crop desiccation just prior to the harvest. We argue that the practice of “ripening” sugar cane with glyphosate may explain the recent

  16. The Celiac Patient Antibody Response to Conventional and Gluten-Removed Beer.

    PubMed

    Allred, Laura K; Lesko, Katherine; McKiernan, Diane; Kupper, Cynthia; Guandalini, Stefano

    2017-03-01

    Enzymatic digestion, or hydrolysis, has been proposed for treating gluten-containing foods and beverages to make them safe for persons with celiac disease (CD). There are no validated testing methods that allow the quantitation of all the hydrolyzed or fermented gluten peptides in foods and beverages that might be harmful to CD patients, making it difficult to assess the safety of hydrolyzed products. This study examines an ELISA-based method to determine whether serum antibody binding of residual peptides in a fermented barley-based product is greater among active-CD patients than a normal control group, using commercial beers as a test case. Sera from 31 active-CD patients and 29 nonceliac control subjects were used to assess the binding of proteins from barley, rice, traditional beer, gluten-free beer, and enzymatically treated (gluten-removed) traditional beer. In the ELISA, none of the subjects' sera bound to proteins in the gluten-free beer. Eleven active-CD patient serum samples demonstrated immunoglobulin A (IgA) or immunoglobulin G (IgG) binding to a barley extract, compared to only one nonceliac control subject. Of the seven active-CD patients who had an IgA binding response to barley, four also responded to traditional beer, and two of these responded to the gluten-removed beer. None of the nonceliac control subjects' sera bound to all three beer samples. Binding of protein fragments in hydrolyzed or fermented foods and beverages by serum from active-CD patients, but not nonceliac control subjects, may indicate the presence of residual peptides that are celiac-specific.

  17. Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for celiac sprue.

    PubMed

    Shan, Lu; Qiao, Shuo-Wang; Arentz-Hansen, Helene; Molberg, Øyvind; Gray, Gary M; Sollid, Ludvig M; Khosla, Chaitan

    2005-01-01

    Dietary gluten proteins from wheat, rye, and barley are the primary triggers for the immuno-pathogenesis of Celiac Sprue, a widespread immune disease of the small intestine. Recent molecular and structural analyses of representative gluten proteins, most notably alpha- and gamma-gliadin proteins from wheat, have improved our understanding of these pathogenic mechanisms. In particular, based on the properties of a 33-mer peptide, generated from alpha-gliadin under physiological conditions, a link between digestive resistance and inflammatory character of gluten has been proposed. Here, we report three lines of investigation in support of this hypothesis. First, biochemical and immunological analysis of deletion mutants of alpha-2 gliadin confirmed that the DQ2 restricted T cell response to the alpha-2 gliadin are directed toward the epitopes clustered within the 33-mer. Second, proteolytic analysis of a representative gamma-gliadin led to the identification of another multivalent 26-mer peptide that was also resistant to further gastric, pancreatic and intestinal brush border degradation, and was a good substrate of human transglutaminase 2 (TG2). Analogous to the 33-mer, the synthetic 26-mer peptide displayed markedly enhanced T cell antigenicity compared to monovalent control peptides. Finally, in silico analysis of the gluten proteome led to the identification of at least 60 putative peptides that share the common characteristics of the 33-mer and the 26-mer peptides. Together, these results highlight the pivotal role of physiologically generated, proteolytically stable, TG2-reactive, multivalent peptides in the immune response to dietary gluten in Celiac Sprue patients. Prolyl endopeptidase treatment was shown to abolish the antigenicity of both the 33-mer and the 26-mer peptides, and was also predicted to have comparable effects on other proline-rich putatively immunotoxic peptides identified from other polypeptides within the gluten proteome.

  18. Identification and Analysis of Multivalent Proteolytically Resistant Peptides from Gluten: Implications for Celiac Sprue

    PubMed Central

    Shan, Lu; Qiao, Shuo-Wang; Arentz-Hansen, Helene; Molberg, Øyvind; Gray, Gary M.; Sollid, Ludvig M.; Khosla, Chaitan

    2005-01-01

    Dietary gluten proteins from wheat, rye and barley are the primary triggers for the immuno-pathogenesis of Celiac Sprue, a widespread immune disease of the small intestine. Recent molecular and structural analyses of representative gluten proteins, most notably α- and γ-gliadin proteins from wheat, have improved our understanding of these pathogenic mechanisms. In particular, based on the properties of a 33-mer peptide, generated from α-gliadin under physiological conditions, a link between digestive resistance and inflammatory character of gluten has been proposed. Here we report three lines of investigation in support of this hypothesis. First, biochemical and immunological analysis of deletion mutants of α-2 gliadin confirmed that the DQ2 restricted T cell response to the α-2 gliadin are directed towards the epitopes clustered within the 33-mer. Second, proteolytic analysis of a representative γ-gliadin led to the identification of another multivalent 26-mer peptide that was also resistant to further gastric, pancreatic and intestinal brush border degradation, and was a good substrate of human transglutaminase 2 (TG2). Analogous to the 33-mer, the synthetic 26-mer peptide displayed markedly enhanced T cell antigenicity compared to monovalent control peptides. Finally, in silico analysis of the gluten proteome led to the identification of at least 60 putative peptides that share the common characteristics of the 33-mer and the 26-mer peptides. Together, these results highlight the pivotal role of physiologically generated, proteolytically stable, TG2-reactive, multivalent peptides in the immune response to dietary gluten in Celiac Sprue patients. Prolyl endopeptidase treatment was shown to abolish the antigenicity of both the 33-mer and the 26-mer peptides, and was also predicted to have comparable effects on other proline-rich putatively immunotoxic peptides identified from other polypeptides within the gluten proteome. PMID:16212427

  19. Gluten contamination of naturally gluten-free flours and starches used by Canadians with celiac disease.

    PubMed

    Koerner, Terence B; Cleroux, Chantal; Poirier, Christine; Cantin, Isabelle; La Vieille, Sébastien; Hayward, Stephen; Dubois, Sheila

    2013-01-01

    A large national investigation into the extent of gluten cross-contamination of naturally gluten-free ingredients (flours and starches) sold in Canada was performed. Samples (n = 640) were purchased from eight Canadian cities and via the internet during the period 2010-2012 and analysed for gluten contamination. The results showed that 61 of the 640 (9.5%) samples were contaminated above the Codex-recommended maximum level for gluten-free products (20 mg kg⁻¹) with a range of 5-7995 mg kg⁻¹. For the ingredients that were labelled gluten-free the contamination range (5-141 mg kg⁻¹) and number of samples were lower (3 of 268). This picture was consistent over time, with approximately the same percentage of samples above 20 mg kg⁻¹ in both the initial set and the subsequent lot. Looking at the total mean (composite) contamination for specific ingredients the largest and most consistent contaminations come from higher fibre ingredients such as soy (902 mg kg⁻¹), millet (272 mg kg⁻¹) and buckwheat (153 mg kg⁻¹). Of the naturally gluten-free flours and starches tested that do not contain a gluten-free label, the higher fibre ingredients would constitute the greatest probability of being contaminated with gluten above 20 mg kg⁻¹.

  20. In vitro models for gluten toxicity: relevance for celiac disease pathogenesis and development of novel treatment options.

    PubMed

    Lindfors, Katri; Rauhavirta, Tiina; Stenman, Satumarja; Mäki, Markku; Kaukinen, Katri

    2012-02-01

    In genetically predisposed individuals, dietary gluten in wheat, rye and barley triggers celiac disease, a systemic autoimmune disorder hallmarked by an extensive small-bowel mucosal immune response. The current conception of celiac disease pathogenesis is that it involves components of both innate and adaptive immunity whose activation typically leads to small-bowel villous atrophy with crypt hyperplasia. Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet excluding all wheat-, rye- and barley-containing food products. During the diet, the clinical symptoms improve and the small-bowel mucosal damage recovers, while re-introduction of gluten into the diet leads to re-appearance of the symptoms and deterioration of the small-bowel mucosal architecture. In view of the restricted nature of the diet, alternative treatment is warranted. Improved understanding of the molecular basis of celiac disease has enabled researchers to suggest other therapeutic approaches. Although there is no animal model reproducing all features of celiac disease, the use of in vitro approaches including a variety of cell lines and the celiac patient small-bowel mucosal biopsy organ culture has generated knowledge about pathogenesis of celiac disease. In these culture systems, gluten induces different effects that can be quantified, thus also enabling studies concerning the efficacy of candidate therapeutic compounds for celiac disease. This review describes the intestinal epithelial cell models, celiac patient T-cell lines and clones, as well as the small-bowel mucosal organ culture methods widely used in studies of celiac disease, and summarizes the major findings obtained with these systems.

  1. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism

    PubMed Central

    Lau, Nga M.; Green, Peter H. R.; Taylor, Annette K.; Hellberg, Dan; Ajamian, Mary; Tan, Caroline Z.; Kosofsky, Barry E.; Higgins, Joseph J.; Rajadhyaksha, Anjali M.; Alaedini, Armin

    2013-01-01

    Objective Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease. Methods Study participants included children (with or without gastrointestinal symptoms) diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) (n = 37), their unaffected siblings (n = 27), and age-matched healthy controls (n = 76). Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles. Results Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). The IgG levels were also higher compared to the unaffected siblings, but did not reach statistical significance. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them (p<0.01). There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed. Conclusions A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody

  2. Gluten Sensitivity

    MedlinePlus

    ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different from ... their small intestine. Some of the symptoms of gluten sensitivity are similar to celiac disease. They include tiredness ...

  3. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease.

    PubMed

    Croese, John; Giacomin, Paul; Navarro, Severine; Clouston, Andrew; McCann, Leisa; Dougall, Annette; Ferreira, Ivana; Susianto, Atik; O'Rourke, Peter; Howlett, Mariko; McCarthy, James; Engwerda, Christian; Jones, Dianne; Loukas, Alex

    2015-02-01

    Celiac disease (CeD) is a common gluten-sensitive autoimmune enteropathy. A gluten-free diet is an effective treatment, but compliance is demanding; hence, new treatment strategies for CeD are required. Parasitic helminths hold promise for treating inflammatory disorders, so we examined the influence of experimental hookworm infection on the predicted outcomes of escalating gluten challenges in CeD subjects. A 52-week study was conducted involving 12 adults with diet-managed CeD. Subjects were inoculated with 20 Necator americanus larvae, and escalating gluten challenges consumed as pasta were subsequently administered: (1) 10 to 50 mg for 12 weeks (microchallenge); (2) 25 mg daily + 1 g twice weekly for 12 weeks (GC-1g); and (3) 3 g daily (60-75 straws of spaghetti) for 2 weeks (GC-3g). Symptomatic, serologic, and histological outcomes evaluated gluten toxicity. Regulatory and inflammatory T cell populations in blood and mucosa were examined. Two gluten-intolerant subjects were withdrawn after microchallenge. Ten completed GC-1g, 8 of whom enrolled in and completed GC-3g. median villous height-to-crypt depth ratios (2.60-2.63; P = .98) did not decrease as predicted after GC-1g, and the mean IgA-tissue transglutaminase titers declined, contrary to the predicted rise after GC-3g. quality of life scores improved (46.3-40.6; P = .05); celiac symptom indices (24.3-24.3; P = .53), intra-epithelial lymphocyte percentages (32.5-35.0; P = .47), and Marsh scores were unchanged by gluten challenge. Intestinal T cells expressing IFNγ were reduced following hookworm infection (23.9%-11.5%; P = .04), with corresponding increases in CD4(+) Foxp3(+) regulatory T cells (0.19%-1.12%; P = .001). Necator americanus and gluten microchallenge promoted tolerance and stabilized or improved all tested indices of gluten toxicity in CeD subjects. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten Free Diet on Diseases Improvement

    PubMed Central

    Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran

    2013-01-01

    Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636

  5. Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide.

    PubMed

    Morón, Belén; Bethune, Michael T; Comino, Isabel; Manyani, Hamid; Ferragud, Marina; López, Manuel Carlos; Cebolla, Angel; Khosla, Chaitan; Sousa, Carolina

    2008-05-28

    Celiac disease is a permanent intolerance to gluten prolamins from wheat, barley, rye and, in some patients, oats. Partially digested gluten peptides produced in the digestive tract cause inflammation of the small intestine. High throughput, immune-based assays using monoclonal antibodies specific for these immunotoxic peptides would facilitate their detection in food and enable monitoring of their enzymatic detoxification. Two monoclonal antibodies, G12 and A1, were developed against a highly immunotoxic 33-mer peptide. The potential of each antibody for quantifying food toxicity for celiac patients was studied. Epitope preferences of G12 and A1 antibodies were determined by ELISA with gluten-derived peptide variants of recombinant, synthetic or enzymatic origin. The recognition sequences of G12 and A1 antibodies were hexameric and heptameric epitopes, respectively. Although G12 affinity for the 33-mer was superior to A1, the sensitivity for gluten detection was higher for A1. This observation correlated to the higher number of A1 epitopes found in prolamins than G12 epitopes. Activation of T cell from gluten digested by glutenases decreased equivalently to the detection of intact peptides by A1 antibody. Peptide recognition of A1 included gliadin peptides involved in the both the adaptive and innate immunological response in celiac disease. The sensitivity and epitope preferences of the A1 antibody resulted to be useful to detect gluten relevant peptides to infer the potential toxicity of food for celiac patients as well as to monitor peptide modifications by transglutaminase 2 or glutenases.

  6. Label-free SPR detection of gluten peptides in urine for non-invasive celiac disease follow-up.

    PubMed

    Soler, Maria; Estevez, M-Carmen; Moreno, Maria de Lourdes; Cebolla, Angel; Lechuga, Laura M

    2016-05-15

    Motivated by the necessity of new and efficient methods for dietary gluten control of celiac patients, we have developed a simple and highly sensitive SPR biosensor for the detection of gluten peptides in urine. The sensing methodology enables rapid and label-free quantification of the gluten immunogenic peptides (GIP) by using G12 mAb. The overall performance of the biosensor has been in-depth optimized and evaluated in terms of sensitivity, selectivity and reproducibility, reaching a limit of detection of 0.33 ng mL(-1). Besides, the robustness and stability of the methodology permit the continuous use of the biosensor for more than 100 cycles with excellent repeatability. Special efforts have been focused on preventing and minimizing possible interferences coming from urine matrix enabling a direct analysis in this fluid without requiring extraction or purification procedures. Our SPR biosensor has proven to detect and identify gluten consumption by evaluating urine samples from healthy and celiac individuals with different dietary gluten conditions. This novel biosensor methodology represents a novel approach to quantify the digested gluten peptides in human urine with outstanding sensitivity in a rapid and non-invasive manner. Our technique should be considered as a promising opportunity to develop Point-of-Care (POC) devices for an efficient, simple and accurate gluten free diet (GFD) monitoring as well as therapy follow-up of celiac disease patients.

  7. Fibromyalgia and non-celiac gluten sensitivity: a description with remission of fibromyalgia.

    PubMed

    Isasi, Carlos; Colmenero, Isabel; Casco, Fernando; Tejerina, Eva; Fernandez, Natalia; Serrano-Vela, José I; Castro, Maria J; Villa, Luis F

    2014-11-01

    Fibromyalgia (FM) syndrome is a disabling clinical condition of unknown cause, and only symptomatic treatment with limited benefit is available. Gluten sensitivity that does not fulfill the diagnostic criteria for celiac disease (CD) is increasingly recognized as a frequent and treatable condition with a wide spectrum of manifestations that overlap with the manifestations of FM, including chronic musculoskeletal pain, asthenia, and irritable bowel syndrome. The aim of this report was to describe 20 selected patients with FM without CD who improved when placed on a gluten-free diet. An anti-transglutaminase assay, duodenal biopsy, and HLA typing were performed in all cases. CD was ruled out by negative anti-transglutaminase assay results and absence of villous atrophy in the duodenal biopsy. All patients had intraepithelial lymphocytosis without villous atrophy. Clinical response was defined as achieving at least one of the following scenarios: remission of FM pain criteria, return to work, return to normal life, or the discontinuation of opioids. The mean follow-up period was 16 months (range 5-31). This observation supports the hypothesis that non-celiac gluten sensitivity may be an underlying cause of FM syndrome.

  8. Circulating gluten-specific FOXP3(+)CD39(+) regulatory T cells have impaired suppressive function in patients with celiac disease.

    PubMed

    Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

    2017-03-08

    Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)(+) Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4(+) T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4(+) T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4(+) T cells were FOXP3(+)CD39(+) Treg cells, which reside within the pool of memory CD4(+)CD25(+)CD127(low)CD45RO(+) Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3(+)CD39(+) Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3(+)CD39(+) Treg cell frequency within circulating gluten-specific CD4(+) T cells after oral gluten challenge of patients with celiac disease. FOXP3(+)CD39(+) Treg cells comprised a major proportion of all circulating gluten-specific CD4(+) T cells but had impaired suppressive function, indicating that Treg cell dysfunction might

  9. Celiac Support Association

    MedlinePlus

    National Celiac Association Navigation About About Us Mission & Goals Officers & Staff Medical & Nutritional Advisors Gluten Free Recipes The Gluten-Free Food ... For Hurricanes Cart Welcome to the National Celiac Association (NCA) The National Celiac Association is a 501( ...

  10. Natural antibiotic expression in celiac disease--correlation with villous atrophy and response to a gluten-free diet.

    PubMed

    Taha, Ali S; Faccenda, Elena; Angerson, Wilson J; Balsitis, Margaret; Kelly, Rodney W

    2005-04-01

    As infection influences the pathogenesis and presentation of celiac disease, we investigated the expression of natural antibiotics in this condition. Twenty-three adults were prospectively studied: 10 controls and 13 subjects with untreated celiac disease. Distal duodenal biopsies were taken at baseline and after 6 months of a gluten-free diet and assessed for the expression of natural antibiotics. Epithelial human beta-defensin 1 in subjects with celiac disease had a median of 0.02 unit at baseline, compared with 0.34 unit in controls (P < 0.001). It correlated negatively with the degree of villous atrophy (r = -0.64, P = 0.019) and rose to 0.04 unit on the gluten-free diet (P = 0.035 vs. baseline, P < 0.001 vs. controls). The expression of other antibiotics was unchanged. The expression of epithelial natural antibiotics is limited in celiac disease.

  11. Characterization of celiac disease related oat proteins: bases for the development of high quality oat varieties suitable for celiac patients

    PubMed Central

    Giménez, María J.; Real, Ana; García-Molina, M. Dolores; Sousa, Carolina; Barro, Francisco

    2017-01-01

    Some studies have suggested that the immunogenicity of oats depends on the cultivar. RP-HPLC has been proposed as a useful technique to select varieties of oats with reduced immunogenicity. The aim of this study was to identify both the avenin protein patterns associated with low gluten content and the available variability for the development of new non-toxic oat cultivars. The peaks of alcohol-soluble avenins of a collection of landraces and cultivars of oats have been characterized based on the RP-HPLC elution times. The immunotoxicity of oat varieties for patients with celiac disease (CD) has been tested using a competitive ELISA based on G12 monoclonal antibody. The oat lines show, on average, seven avenin peaks giving profiles with certain similarities. Based on this similarity, most of the accessions have been grouped into avenin patterns. The variability of RP-HPLC profiles of the collection is great, but not sufficient to uniquely identify the different varieties of the set. Overall, the immunogenicity of the collection is less than 20 ppm. However, there is a different distribution of toxicity ranges between the different peak patterns. We conclude that the RP-HPLC technique is useful to establish groups of varieties differing in degree of toxicity for CD patients. PMID:28209962

  12. Characterization of celiac disease related oat proteins: bases for the development of high quality oat varieties suitable for celiac patients.

    PubMed

    Giménez, María J; Real, Ana; García-Molina, M Dolores; Sousa, Carolina; Barro, Francisco

    2017-02-17

    Some studies have suggested that the immunogenicity of oats depends on the cultivar. RP-HPLC has been proposed as a useful technique to select varieties of oats with reduced immunogenicity. The aim of this study was to identify both the avenin protein patterns associated with low gluten content and the available variability for the development of new non-toxic oat cultivars. The peaks of alcohol-soluble avenins of a collection of landraces and cultivars of oats have been characterized based on the RP-HPLC elution times. The immunotoxicity of oat varieties for patients with celiac disease (CD) has been tested using a competitive ELISA based on G12 monoclonal antibody. The oat lines show, on average, seven avenin peaks giving profiles with certain similarities. Based on this similarity, most of the accessions have been grouped into avenin patterns. The variability of RP-HPLC profiles of the collection is great, but not sufficient to uniquely identify the different varieties of the set. Overall, the immunogenicity of the collection is less than 20 ppm. However, there is a different distribution of toxicity ranges between the different peak patterns. We conclude that the RP-HPLC technique is useful to establish groups of varieties differing in degree of toxicity for CD patients.

  13. Design of azidoproline containing gluten peptides to suppress CD4+ T-cell responses associated with celiac disease.

    PubMed

    Kapoerchan, Varsha V; Wiesner, Martina; Overhand, Mark; van der Marel, Gijs A; Koning, Frits; Overkleeft, Herman S

    2008-02-15

    Celiac disease is an intestinal disease caused by intolerance for gluten, a common protein in food. A life-long gluten-free diet is the only available treatment. As it is well established that the interaction between proline-rich gluten derived peptides and the human HLA-DQ2 molecules induces immune responses that lead to disease development, we have now designed a series of gluten peptides in which proline residues were replaced by azidoprolines. These peptides were found to bind to HLA-DQ2 with an affinity similar to that of the natural gluten peptide. Moreover, some of these peptides were found to be non-immunogenic and block gluten induced immune responses. These can thus serve as lead compounds for the development of HLA-DQ2 blocker peptides.

  14. Gluten consumption during late pregnancy and risk of celiac disease in the offspring: the TEDDY birth cohort12

    PubMed Central

    Uusitalo, Ulla; Lee, Hye-Seung; Aronsson, Carin Andrén; Yang, Jimin; Virtanen, Suvi M; Norris, Jill; Agardh, Daniel

    2015-01-01

    Background: Maternal diet during pregnancy has been proposed to increase the risk of autoimmune diseases. Objective: The objective was to investigate the association between maternal consumption of gluten-containing foods during late pregnancy and subsequent risk of celiac disease in the offspring. Design: Genetically susceptible children prospectively followed from birth were screened annually for tissue transglutaminase autoantibodies (tTGAs). Children testing persistently positive for tTGAs were further evaluated for celiac disease. Diagnosis of celiac disease was confirmed by intestinal biopsy or was considered likely if the mean tTGA concentration was >100 units in 2 consecutive samples. A questionnaire on the mother’s diet in late pregnancy was completed by 3–4.5 mo postpartum. Mothers were divided into 3 groups based on the tertiles of their consumption of gluten-containing foods (servings/d). The association between maternal gluten-containing food consumption and the risk of celiac disease was studied by using a time-to-event analysis. Results: At the time of analysis, 359 (5%) of the 6546 children developed celiac disease. Compared with the middle category of maternal gluten-containing food consumption (servings/d), low (HR: 0.87; 95% CI: 0.67, 1.13; P = 0.296) and high (HR: 0.84; 95% CI: 0.65, 1.09; P = 0.202) consumption was not associated with risk of celiac disease in the child after adjustment for country, human leukocyte antigen genotype, family history of celiac disease, maternal education, and sex of the child. Median maternal daily consumption frequency of gluten-containing foods was higher (P < 0.0001) in Finland (5.3; IQR: 3.9–6.9), Germany (4.3; IQR: 3.1–5.5), and Sweden (3.7; IQR: 2.8–4.9) than in the United States (3.4; IQR: 2.3–4.9). No significant interaction was found between country of residence and the mothers’ consumption of gluten-containing foods in relation to risk of celiac disease. Conclusion: The frequency of gluten

  15. Gluten consumption during late pregnancy and risk of celiac disease in the offspring: the TEDDY birth cohort.

    PubMed

    Uusitalo, Ulla; Lee, Hye-Seung; Aronsson, Carin Andrén; Yang, Jimin; Virtanen, Suvi M; Norris, Jill; Agardh, Daniel

    2015-11-01

    Maternal diet during pregnancy has been proposed to increase the risk of autoimmune diseases. The objective was to investigate the association between maternal consumption of gluten-containing foods during late pregnancy and subsequent risk of celiac disease in the offspring. Genetically susceptible children prospectively followed from birth were screened annually for tissue transglutaminase autoantibodies (tTGAs). Children testing persistently positive for tTGAs were further evaluated for celiac disease. Diagnosis of celiac disease was confirmed by intestinal biopsy or was considered likely if the mean tTGA concentration was >100 units in 2 consecutive samples. A questionnaire on the mother's diet in late pregnancy was completed by 3-4.5 mo postpartum. Mothers were divided into 3 groups based on the tertiles of their consumption of gluten-containing foods (servings/d). The association between maternal gluten-containing food consumption and the risk of celiac disease was studied by using a time-to-event analysis. At the time of analysis, 359 (5%) of the 6546 children developed celiac disease. Compared with the middle category of maternal gluten-containing food consumption (servings/d), low (HR: 0.87; 95% CI: 0.67, 1.13; P = 0.296) and high (HR: 0.84; 95% CI: 0.65, 1.09; P = 0.202) consumption was not associated with risk of celiac disease in the child after adjustment for country, human leukocyte antigen genotype, family history of celiac disease, maternal education, and sex of the child. Median maternal daily consumption frequency of gluten-containing foods was higher (P < 0.0001) in Finland (5.3; IQR: 3.9-6.9), Germany (4.3; IQR: 3.1-5.5), and Sweden (3.7; IQR: 2.8-4.9) than in the United States (3.4; IQR: 2.3-4.9). No significant interaction was found between country of residence and the mothers' consumption of gluten-containing foods in relation to risk of celiac disease. The frequency of gluten-containing food consumption during late pregnancy is not

  16. Breast-feeding duration and gluten introduction among mothers with celiac disease.

    PubMed

    Welander, Adina; Montgomery, Scott; Ludvigsson, Johnny; Ludvigsson, Jonas F

    2014-07-01

    Both breast-feeding duration and age at gluten introduction have been implicated in the pathogenesis of celiac disease (CD). We hypothesized that parental CD affects the feeding pattern of the offspring, mediated by parental health awareness increasing adherence to infant feeding guidelines. Prospectively collected infant feeding data were obtained through the All Babies in Southeast Sweden study. Information regarding infant feeding was available in 9414 children. Twenty-two mothers had a history of biopsy-verified CD before delivery of a child in the study, and 9392 mothers had no diagnosis of CD before birth and thus constituted the unexposed or control population. Cox regression was used to compare the risk of early weaning and gluten introduction according to parental CD status, and logistic regression to assess whether mothers with CD were more likely to breast-feed their children at gluten introduction. Some 63% of children were breast-fed for at least 9 months. We found no association between maternal CD and early weaning (adjusted hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6-1.7), or between paternal CD and early weaning (HR 0.5, 95% CI 0.1-1.9). Sixty percent of children were introduced to gluten in months 5 and 6. Maternal CD was not associated with age at gluten introduction (adjusted HR 0.8, 95% CI 0.6-1.3). There was no statistically significant association between maternal CD and breast-feeding at the time of gluten introduction (odds ratio 1.4, 95% CI 0.4-4.7). Feeding patterns do not seem to vary between offspring and mothers with CD and those without.

  17. Biomarkers to Monitor Gluten-Free Diet Compliance in Celiac Patients

    PubMed Central

    Moreno, María de Lourdes; Rodríguez-Herrera, Alfonso; Sousa, Carolina; Comino, Isabel

    2017-01-01

    Gluten-free diet (GFD) is the only treatment for celiac disease (CD). There is a general consensus that strict GFD adherence in CD patients leads to full clinical and histological remission accompanied by improvement in quality of life and reduced long-term complications. Despite the importance of monitoring the GFD, there are no clear guidelines for assessing the outcome or for exploring its adherence. Available methods are insufficiently accurate to identify occasional gluten exposure that may cause intestinal mucosal damage. Serological tests are highly sensitive and specific for diagnosis, but do not predict recovery and are not useful for follow-up. The use of serial endoscopies, it is invasive and impractical for frequent monitoring, and dietary interview can be subjective. Therefore, the detection of gluten immunogenic peptides (GIP) in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients. These simple immunoassays in human samples could overcome some key unresolved scientific and clinical problems in CD management. It is a significant advance that opens up new possibilities for the clinicians to evaluate the CD treatment, GFD compliance, and improvement in the quality of life of CD patients. PMID:28067823

  18. Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity.

    PubMed

    Verdu, Elena F; Armstrong, David; Murray, Joseph A

    2009-06-01

    The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)- DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions.

  19. Reintroduction of gluten following flour transamidation in adult celiac patients: a randomized, controlled clinical study.

    PubMed

    Mazzarella, Giuseppe; Salvati, Virginia M; Iaquinto, Gaetano; Stefanile, Rosita; Capobianco, Federica; Luongo, Diomira; Bergamo, Paolo; Maurano, Francesco; Giardullo, Nicola; Malamisura, Basilio; Rossi, Mauro

    2012-01-01

    A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (P = 0.04) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, P = 0.06). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (P = 0.63), Marsh-Oberhuber grading (P = 0.08), or intestinal IFN-γ mRNA (P > 0.05). Creatinine clearance did not vary after 90 days of treatment (P = 0.46). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.

  20. Reintroduction of Gluten Following Flour Transamidation in Adult Celiac Patients: A Randomized, Controlled Clinical Study

    PubMed Central

    Mazzarella, Giuseppe; Salvati, Virginia M.; Iaquinto, Gaetano; Stefanile, Rosita; Capobianco, Federica; Luongo, Diomira; Bergamo, Paolo; Maurano, Francesco; Giardullo, Nicola; Malamisura, Basilio; Rossi, Mauro

    2012-01-01

    A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (P = 0.04) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, P = 0.06). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (P = 0.63), Marsh-Oberhuber grading (P = 0.08), or intestinal IFN-γ mRNA (P > 0.05). Creatinine clearance did not vary after 90 days of treatment (P = 0.46). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function. PMID:22899947

  1. Cutaneous Manifestations of Non-Celiac Gluten Sensitivity: Clinical Histological and Immunopathological Features.

    PubMed

    Bonciolini, Veronica; Bianchi, Beatrice; Del Bianco, Elena; Verdelli, Alice; Caproni, Marzia

    2015-09-15

    The dermatological manifestations associated with intestinal diseases are becoming more frequent, especially now when new clinical entities, such as Non-Celiac Gluten Sensitivity (NCGS), are identified. The existence of this new entity is still debated. However, many patients with diagnosed NCGS that present intestinal manifestations have skin lesions that need appropriate characterization. We involved 17 patients affected by NCGS with non-specific cutaneous manifestations who got much better after a gluten free diet. For a histopathological and immunopathological evaluation, two skin samples from each patient and their clinical data were collected. The median age of the 17 enrolled patients affected by NCGS was 36 years and 76% of them were females. On the extensor surfaces of upper and lower limbs in particular, they all presented very itchy dermatological manifestations morphologically similar to eczema, psoriasis or dermatitis herpetiformis. This similarity was also confirmed histologically, but the immunopathological analysis showed the prevalence of deposits of C3 along the dermo-epidermal junction with a microgranular/granular pattern (82%). The exact characterization of new clinical entities such as Cutaneous Gluten Sensitivity and NCGS is an important objective both for diagnostic and therapeutic purposes, since these are patients who actually benefit from a GFD (Gluten Free Diet) and who do not adopt it only for fashion.

  2. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity

    PubMed Central

    Hollon, Justin; Leonard Puppa, Elaine; Greenwald, Bruce; Goldberg, Eric; Guerrerio, Anthony; Fasano, Alessio

    2015-01-01

    Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity. PMID:25734566

  3. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity.

    PubMed

    Hollon, Justin; Puppa, Elaine Leonard; Greenwald, Bruce; Goldberg, Eric; Guerrerio, Anthony; Fasano, Alessio

    2015-02-27

    Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.

  4. Lack of Serologic Evidence to Link IgA Nephropathy with Celiac Disease or Immune Reactivity to Gluten

    PubMed Central

    Moeller, Sina; Canetta, Pietro A.; Taylor, Annette K.; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H.; Kiryluk, Krzysztof; Alaedini, Armin

    2014-01-01

    IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy. PMID:24732864

  5. The association between semaphorin 3A levels and gluten-free diet in patients with celiac disease.

    PubMed

    Kessel, Aharon; Lin, Chen; Vadasz, Zahava; Peri, Regina; Eiza, Nasren; Berkowitz, Drora

    2017-05-11

    Celiac disease (CD) is an inflammatory disease affecting the small intestine. We aim to assess serum level and expression of semaphorin 3A (Sema3A) on T regulatory (Treg) cells in CD patients. Twenty-six newly diagnosed celiac patients, 13 celiac patients on a gluten-free diet and 16 healthy controls included in the study. Sema3A protein level in the serum of celiac patients was significantly higher compared to healthy group (7.17±1.8ng/ml vs. 5.67±1.5ng/ml, p=0.012). Sema3A expression on Treg cells was statistically lower in celiac patients compared to healthy subjects (p=0.009) and significantly lower in celiac patients compared to celiac patients on gluten free diet (p=0.04). Negative correlation was found between Sema3A on Teg cells and the level of IgA anti-tTG antibodies (r=-0.346, p<0.01) and anti-DGP (r=-0.448, p<0.01). This study suggests involvement of the Sema3A in the pathogenesis of CD. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Especially for Women: Could Gluten be Causing Your Symptoms?

    MedlinePlus

    ... gluten-related disorders (celiac disease or non-celiac gluten sensitivity) are also more likely to exist in women ... women than men. celiac disease and non-celiac gluten sensitivity. Depression & Anxiety More common among women than men. ...

  7. Cereal-based gluten-free food: how to reconcile nutritional and technological properties of wheat proteins with safety for celiac disease patients.

    PubMed

    Lamacchia, Carmela; Camarca, Alessandra; Picascia, Stefania; Di Luccia, Aldo; Gianfrani, Carmen

    2014-01-29

    The gluten-free diet is, to date, the only efficacious treatment for patients with Celiac Disease. In recent years, the impressive rise of Celiac Disease incidence, dramatically prompted changes in the dietary habit of an increasingly large population, with a rise in demand of gluten-free products. The formulation of gluten-free bakery products presents a formidable challenge to cereal technologists. As wheat gluten contributes to the formation of a strong protein network, that confers visco-elasticity to the dough and allows the wheat flour to be processed into a wide range of products, the preparation of cereal-based gluten-free products is a somehow difficult process. This review focuses on nutritional and technological quality of products made with gluten-free cereals available on the market. The possibility of using flour from naturally low toxic ancient wheat species or detoxified wheat for the diet of celiacs is also discussed.

  8. Cereal-Based Gluten-Free Food: How to Reconcile Nutritional and Technological Properties of Wheat Proteins with Safety for Celiac Disease Patients

    PubMed Central

    Lamacchia, Carmela; Camarca, Alessandra; Picascia, Stefania; Di Luccia, Aldo; Gianfrani, Carmen

    2014-01-01

    The gluten-free diet is, to date, the only efficacious treatment for patients with Celiac Disease. In recent years, the impressive rise of Celiac Disease incidence, dramatically prompted changes in the dietary habit of an increasingly large population, with a rise in demand of gluten-free products. The formulation of gluten-free bakery products presents a formidable challenge to cereal technologists. As wheat gluten contributes to the formation of a strong protein network, that confers visco-elasticity to the dough and allows the wheat flour to be processed into a wide range of products, the preparation of cereal-based gluten-free products is a somehow difficult process. This review focuses on nutritional and technological quality of products made with gluten-free cereals available on the market. The possibility of using flour from naturally low toxic ancient wheat species or detoxified wheat for the diet of celiacs is also discussed. PMID:24481131

  9. Salivary and fecal microbiota and metabolome of celiac children under gluten-free diet.

    PubMed

    De Angelis, Maria; Vannini, Lucia; Di Cagno, Raffaella; Cavallo, Noemi; Minervini, Fabio; Francavilla, Ruggiero; Ercolini, Danilo; Gobbetti, Marco

    2016-12-19

    Celiac disease (CD) is an inflammatory autoimmune disorder resulting from the combination of genetic predisposition and gluten ingestion. A life-long gluten free diet (GFD) is the only therapeutic approach. Dysbiosis, which can precede the CD pathogenesis and/or persist when subjects are on GFD, is reviewed and discussed. Salivary microbiota and metabolome differed between healthy and celiac children treated under GFD (T-CD) for at least two years. The type of GFD (African- vs Italian-style) modified the microbiota and metabolome of Saharawi T-CD children. Different studies showed bacterial dysbiosis at duodenal and/or fecal level of patients with active untreated CD (U-CD) and T-CD compared to healthy subjects. The ratio of protective anti-inflammatory bacteria such as Lactobacillus-Bifidobacterium to potentially harmful Bacteroides-Enterobacteriaceae was the lowest in U-CD and T-CD children. In agreement with dysbiosis, serum, fecal and urinary metabolome from U-CD and T-CD patients showed altered levels of free amino acids and volatile organic compounds. However, consensus across studies defining specific bacteria and metabolites in U-CD or T-CD patients is still lacking. Future research efforts are required to determine the relationships between CD and oral and intestinal microbiotas to improve the composition of GFD for restoring the gut dysbiosis as a preventative or therapeutic approach for CD. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity

    PubMed Central

    2014-01-01

    Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial

  11. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity.

    PubMed

    Volta, Umberto; Bardella, Maria Teresa; Calabrò, Antonino; Troncone, Riccardo; Corazza, Gino Roberto

    2014-05-23

    Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3-81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between

  12. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    PubMed Central

    Rana, Surinder S.; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K.

    2016-01-01

    Background Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Methods Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Results Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. Conclusion EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet. PMID:27366039

  13. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    PubMed

    Rana, Surinder S; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K

    2016-01-01

    Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet.

  14. Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1.

    PubMed

    Krifa, F; Knani, L; Sakly, W; Ghedira, I; Essoussi, A S; Boukadida, J; Ben Hadj Hamida, F

    2010-01-01

    A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the left eye. The right eye examination was unremarkable. Slit-lamp examination revealed few small and fine keratic precipitates. We noted 2+ flare in the vitreous. There was no choroiditis, papillitis or retinal vasculitis. No aetiology was found. The patient was treated by topical and systemic corticosteroids without any improvement. Celiac disease was discovered by the presence of celiac antibodies in the work-up of joint pain and diabetes mellitus type 1. Antiendomysium antibodies and anti-transglutaminase antibodies were both positive. A small bowel biopsy confirmed celiac disease. A gluten free diet was set up and corticosteroids were tapered off. Recovery of the uveitis was obvious during gluten free diet and normalized within two months.

  15. Symptomatic efficacy of buckwheat products in Non-Celiac Gluten Sensitivity (NCGS).

    PubMed

    Dinu, Monicau; Macchia, Donatella; Pagliai, Giuditta; Gori, Anna Maria; Cesari, Francesca; Marcucci, Rossella; Sofi, Francesco; Casini, Alessandro

    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). 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. 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%). 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.

  16. Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects.

    PubMed

    Giacomin, Paul; Zakrzewski, Martha; Croese, John; Su, Xiaopei; Sotillo, Javier; McCann, Leisa; Navarro, Severine; Mitreva, Makedonka; Krause, Lutz; Loukas, Alex; Cantacessi, Cinzia

    2015-09-18

    The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis.

  17. A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge

    PubMed Central

    Leffler, Daniel A; Kelly, C P; Abdallah, H Z; Colatrella, A M; Harris, L A; Leon, F; Arterburn, L A; Paterson, B M; Lan, Z H; Murray, J A

    2012-01-01

    OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm

  18. Effects of Gluten Intake on Risk of Celiac Disease: a case–control study on a Swedish birth cohort

    PubMed Central

    Aronsson, Carin Andrén; Lee, Hye-Seung; Koletzko, Sibylle; Uusitalo, Ulla; Yang, Jimin; Virtanen, Suvi M.; Liu, Edwin; Lernmark, Åke; Norris, Jill M.; Agardh, Daniel

    2015-01-01

    Background & Aims It is not clear how intake of gluten during infancy affects subsequent risk of celiac disease. We investigated whether gluten intake before 2 years of age increases risk for celiac disease in genetically susceptible children. Methods We performed a case–control study of 436 pairs of children, generated from a database of 2525 children with genetic susceptibility to celiac disease in Sweden, matched for sex, birth year, and HLA genotype from September 2004 and February 2010. Children were screened annually for celiac disease using an assay for tissue transglutaminase autoantibodies (tTGA). Intestinal biopsies were collected from children who tested positive for tTGA to confirm the presence of celiac disease. Gluten intake was calculated from 3-day food records collected when the children were 9, 12, 18 and 24 months old. Results Breastfeeding duration (median 32 weeks) and age at first introduction to gluten (median 22 weeks) did not differ between cases and tTGA-negative children (controls). At the visit prior to tTGA seroconversion, cases reported a larger intake of gluten (median 4.9 g/day) than controls (median 3.9 g/day) (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13–1.46; P=.0002). More cases consumed amounts of gluten in the upper 3rd tertile (i.e. >5.0 g/day) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70–4.13; P<.0001). This increase in risk was similar for children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61–6.30; P=.001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08≥4.62; P=.030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90–6.54; P=.079). Conclusions Intake of gluten before 2 years of age increases risk of celiac disease at least 2-fold in children with genetic risk factors for this disease. This association did not differ among HLA-DR3-DQ2 haplotypes. These findings may be taken into account for future infant feeding recommendations. PMID

  19. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces123

    PubMed Central

    Comino, Isabel; Real, Ana; Vivas, Santiago; Síglez, Miguel Ángel; Caminero, Alberto; Nistal, Esther; Casqueiro, Javier; Rodríguez-Herrera, Alfonso; Cebolla, Ángel

    2012-01-01

    Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available. Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces. Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody. Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients. Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867. PMID:22258271

  20. Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue

    PubMed Central

    de Souza, M. Cristina P.; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C.; Djilali-Saiah, Idriss

    2016-01-01

    The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet. PMID:27446824

  1. Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue.

    PubMed

    de Souza, M Cristina P; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C; Djilali-Saiah, Idriss

    2016-01-01

    The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet.

  2. Celiac Disease and Dermatologic Manifestations: Many Skin Clue to Unfold Gluten-Sensitive Enteropathy

    PubMed Central

    Caproni, Marzia; Bonciolini, Veronica; D'Errico, Antonietta; Antiga, Emiliano; Fabbri, Paolo

    2012-01-01

    Cutaneous manifestations of intestinal diseases are increasingly reported both in the adult and in the children, and this association cannot longer be considered a simple random. Besides the well-known association between celiac disease (CD) and dermatitis herpetiformis (DH), considered as the cutaneous manifestation of gluten-dependent enteropathy, is more frequently reported also the association with other mucocutaneous diseases. Among these there are both autoimmune, allergic, and inflammatory diseases, but also a more heterogeneous group called miscellaneous. The knowledge about pathogenic, epidemiological, clinical, and diagnostic aspects of CD is increasing in recent years as well as those about DH, but some aspects still remain to be defined, in particular the possible pathogenetic mechanisms involved in the association between both CD and DH and CD and other immunological skin diseases. The aim of this paper is to describe the skin diseases frequently associated with CD, distinguishing them from those which have a relationship probably just coincidental. PMID:22693492

  3. Reversal of IgM deficiency following a gluten-free diet in seronegative celiac disease

    PubMed Central

    Montenegro, Lucia; Piscitelli, Domenico; Giorgio, Floriana; Covelli, Claudia; Fiore, Maria Grazia; Losurdo, Giuseppe; Iannone, Andrea; Ierardi, Enzo; Di Leo, Alfredo; Principi, Mariabeatrice

    2014-01-01

    Selective IgM deficiency (sIGMD) is very rare; it may be associated with celiac disease (CD). We present the case of an 18-year-old man with sIGMD masking seronegative CD. Symptoms included abdominal pain, diarrhea and weight loss. Laboratory tests showed reduced IgM, DQ2-HLA and negative anti-transglutaminase. Villous atrophy and diffuse immature lymphocytes were observed at histology. Tissue transglutaminase mRNA mucosal levels showed a 6-fold increase. The patient was treated with a gluten-free diet (GFD) and six months later the symptoms had disappeared, the villous architecture was restored and mucosal tissue transglutaminase mRNA was comparable to that of healthy subjects. After 1 year of GFD, a complete restoration of normal IgM values was observed and duodenal biopsy showed a reduction of immature lymphocytes and normal appearance of mature immune cells. PMID:25516687

  4. Osteoporosis reversibility in a patient with celiac disease and primary autoimmune hypothyroidism on gluten free diet--a case report.

    PubMed

    Kovačev-Zavišić, Branka; Ičin, Tijana; Novaković-Paro, Jovanka; Medić-Stojanoska, Milica; Bajkin, Ivana

    2015-01-01

    Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism. Biochemical bone markers show predominance of bone resorption, thus making the bisphosphonates the first line therapy option. Intestinal mucosal changes are reversible on gluten-free diet. Osteoporosis reversibility is also possible, provided postmenopausal osteoporosis risk factors independent from celiac disease are not present. We presented a postmenopausal woman with at least a 10-year history of celiac disease prior to diagnosis, which had overt secondary hyperparathyroidism with insufficient status of vitamin D and a significant bone mass reduction. At the time of diagnosis of celiac disease the patient was receiving 250 μg of levothyroxine daily without achieving optimal substitution. Three years after the initiation of gluten-free diet the patient was without any signs and symptoms of the disease. All laboratory findings were within normal range. It was decided to treat the underlying disease and to supplement calcium and vitamin D without the initiation of bisphosponate therapy. Osteoporosis regression justified this therapeutic approach. The presence of primary autoimmune hypothyroidism makes this case specific, since the inability for optimal substitution therapy with a high daily dose of levothyroxine provoked the suspicion of celiac disease.

  5. Celiac disease and school food service in Piedmont Region: Evaluation of gluten-free meal.

    PubMed

    Bioletti, L; Capuano, M T; Vietti, F; Cesari, L; Emma, L; Leggio, K; Fransos, L; Marzullo, A; Ropolo, S; Strumia, C

    2016-01-01

    The Law 123/2005 recognizes celiac disease as a social disease and so Ministry of Public Health annually allocates specific resources to Regions for managing gluten-free meals in school canteens. Therefore in 2009 Piedmont Region approved a specific project, in collaboration with Food Hygiene and Nutrition Department (SIAN) of several ASL (Local Health Authority), including ASL TO3 as regional leader, and the "Italian Celiac Association - Piedmont and Valle d'Aosta". This project was intended to facilitate the natural integration of celiac people in social life. A retrospective analysis of data has been carried out to assess the management of gluten- free meal of school food services in Piedmont Region in 2010. Furthermore the intervention efficacy has been evaluated comparing the critical points observed in 2010 and 2012. The object of the study includes primary and secondary schools that have provided gluten-free food service in Piedmont Region. These school were examined by SIAN staff. (the examination included the check of hygienic aspects and qualitative assessment of the meal). The data were collected using the same checklist throughout the region. All data were included in the unified regional system ("Reteunitaria"). The results show that 29% of the sampled schools (277) are acceptable in all eight sections (supply, storage, process analysis, equipment check, packaging and transport, distribution of meals, self-control plan and qualitative assessment), whereas 71% are inadequate for at least one of the profiles (60% does not perform the qualitative valuation of service) and in 18% of schools three to seven insufficiencies are observed. Correlations between the number of total insufficiencies and the most critical sections of the check list were performed (with lower scores in "good") such as process analysis, distribution of meals, self-control plan and qualitative assessment. The analysis process has achieved a high score in the field of deficiency for at

  6. Socioeconomic Impacts of Gluten-Free Diet among Saudi Children with Celiac Disease

    PubMed Central

    El Mouzan, Mohammad I.; Saeed, Elshazaly; Alanazi, Aziz; Alghamdi, Sharifa; Anil, Shirin; Assiri, Asaad

    2016-01-01

    Purpose To determine the socio-economic impact of gluten free diet (GFD) on Saudi children and their families. Methods A cross-sectional study was conducted in which an online questionnaire was sent to all families registered in the Saudi celiac patients support group. We included only children (age 18 years of age and younger) with biopsy-confirmed celiac disease (CD). Results A total of 113 children were included in the final analysis, the median age was 9.9 years; 62.8% were females. One hundred (88.5%) of the participating families reported that GFD food was not easily available in their areas, 17% of them reported that it was not available at all in their area. One hundred and six (93.8%) reported that the price of GFD food was very expensive and 70 (61.9%) families that the diet was heavily affecting their family budget. Significant social difficulties were reported among the participating families and their children including interference with the child's interaction with other children (49.6%), the families' ability to attend social gatherings (60.2%), the families' ability to eat in restaurants (73.5%), and the families' ability to travel (58.4%). Conclusion There is significant negative socio-economic impact of GFD on children with CD & their families. Health care providers should be aware of these psycho-social difficulties and be well trained to provide a proper education and psychological support for these patients and their families. PMID:27738597

  7. Socioeconomic Impacts of Gluten-Free Diet among Saudi Children with Celiac Disease.

    PubMed

    Sarkhy, Ahmed; El Mouzan, Mohammad I; Saeed, Elshazaly; Alanazi, Aziz; Alghamdi, Sharifa; Anil, Shirin; Assiri, Asaad

    2016-09-01

    To determine the socio-economic impact of gluten free diet (GFD) on Saudi children and their families. A cross-sectional study was conducted in which an online questionnaire was sent to all families registered in the Saudi celiac patients support group. We included only children (age 18 years of age and younger) with biopsy-confirmed celiac disease (CD). A total of 113 children were included in the final analysis, the median age was 9.9 years; 62.8% were females. One hundred (88.5%) of the participating families reported that GFD food was not easily available in their areas, 17% of them reported that it was not available at all in their area. One hundred and six (93.8%) reported that the price of GFD food was very expensive and 70 (61.9%) families that the diet was heavily affecting their family budget. Significant social difficulties were reported among the participating families and their children including interference with the child's interaction with other children (49.6%), the families' ability to attend social gatherings (60.2%), the families' ability to eat in restaurants (73.5%), and the families' ability to travel (58.4%). There is significant negative socio-economic impact of GFD on children with CD & their families. Health care providers should be aware of these psycho-social difficulties and be well trained to provide a proper education and psychological support for these patients and their families.

  8. Celiac Disease

    MedlinePlus

    ... immune disease in which people can't eat gluten because it will damage their small intestine. If you have celiac disease and eat foods with gluten, your immune system responds by damaging the small ...

  9. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients

    PubMed Central

    Comino, Isabel; Fernández-Bañares, Fernando; Esteve, María; Ortigosa, Luís; Castillejo, Gemma; Fambuena, Blanca; Ribes-Koninckx, Carmen; Sierra, Carlos; Rodríguez-Herrera, Alfonso; Salazar, José Carlos; Caunedo, Ángel; Marugán-Miguelsanz, J M; Garrote, José Antonio; Vivas, Santiago; lo Iacono, Oreste; Nuñez, Alejandro; Vaquero, Luis; Vegas, Ana María; Crespo, Laura; Fernández-Salazar, Luis; Arranz, Eduardo; Jiménez-García, Victoria Alejandra; Antonio Montes-Cano, Marco; Espín, Beatriz; Galera, Ana; Valverde, Justo; Girón, Francisco José; Bolonio, Miguel; Millán, Antonio; Cerezo, Francesc Martínez; Guajardo, César; Alberto, José Ramón; Rosinach, Mercé; Segura, Verónica; León, Francisco; Marinich, Jorge; Muñoz-Suano, Alba; Romero-Gómez, Manuel; Cebolla, Ángel; Sousa, Carolina

    2016-01-01

    Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. Methods: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Results: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Conclusions: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397. PMID:27644734

  10. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

    PubMed

    Comino, Isabel; Fernández-Bañares, Fernando; Esteve, María; Ortigosa, Luís; Castillejo, Gemma; Fambuena, Blanca; Ribes-Koninckx, Carmen; Sierra, Carlos; Rodríguez-Herrera, Alfonso; Salazar, José Carlos; Caunedo, Ángel; Marugán-Miguelsanz, J M; Garrote, José Antonio; Vivas, Santiago; Lo Iacono, Oreste; Nuñez, Alejandro; Vaquero, Luis; Vegas, Ana María; Crespo, Laura; Fernández-Salazar, Luis; Arranz, Eduardo; Jiménez-García, Victoria Alejandra; Antonio Montes-Cano, Marco; Espín, Beatriz; Galera, Ana; Valverde, Justo; Girón, Francisco José; Bolonio, Miguel; Millán, Antonio; Cerezo, Francesc Martínez; Guajardo, César; Alberto, José Ramón; Rosinach, Mercé; Segura, Verónica; León, Francisco; Marinich, Jorge; Muñoz-Suano, Alba; Romero-Gómez, Manuel; Cebolla, Ángel; Sousa, Carolina

    2016-10-01

    Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

  11. Identification of food-grade subtilisins as gluten-degrading enzymes to treat celiac disease.

    PubMed

    Wei, Guoxian; Tian, Na; Siezen, Roland; Schuppan, Detlef; Helmerhorst, Eva J

    2016-09-01

    Gluten are proline- and glutamine-rich proteins present in wheat, barley, and rye and contain the immunogenic sequences that drive celiac disease (CD). Rothia mucilaginosa, an oral microbial colonizer, can cleave these gluten epitopes. The aim was to isolate and identify the enzymes and evaluate their potential as novel enzyme therapeutics for CD. The membrane-associated R. mucilaginosa proteins were extracted and separated by DEAE chromatography. Enzyme activities were monitored with paranitroanilide-derivatized and fluorescence resonance energy transfer (FRET) peptide substrates, and by gliadin zymography. Epitope elimination was determined in R5 and G12 ELISAs. The gliadin-degrading Rothia enzymes were identified by LC-ESI-MS/MS as hypothetical proteins ROTMU0001_0241 (C6R5V9_9MICC), ROTMU0001_0243 (C6R5W1_9MICC), and ROTMU0001_240 (C6R5V8_9MICC). A search with the Basic Local Alignment Search Tool revealed that these are subtilisin-like serine proteases belonging to the peptidase S8 family. Alignment of the major Rothia subtilisins indicated that all contain the catalytic triad with Asp (D), His (H), and Ser (S) in the D-H-S order. They cleaved succinyl-Ala-Ala-Pro-Phe-paranitroanilide, a substrate for subtilisin with Pro in the P2 position, as in Tyr-Pro-Gln and Leu-Pro-Tyr in gluten, which are also cleaved. Consistently, FRET substrates of gliadin immunogenic epitopes comprising Xaa-Pro-Xaa motives were rapidly hydrolyzed. The Rothia subtilisins and two subtilisins from Bacillus licheniformis, subtilisin A and the food-grade Nattokinase, efficiently degraded the immunogenic gliadin-derived 33-mer peptide and the immunodominant epitopes recognized by the R5 and G12 antibodies. This study identified Rothia and food-grade Bacillus subtilisins as promising new candidates for enzyme therapeutics in CD.

  12. Predictors of dietary gluten avoidance in adults without a prior diagnosis of celiac disease.

    PubMed

    Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J; Camargo, Carlos A

    2015-01-01

    Prior studies have shown that dietary gluten avoidance (DGA) is relatively common in children without previously diagnosed celiac disease (CD), and several clinical predictors of DGA have been found. However, available data on predictors of DGA in adults without diagnosed CD are limited. The aim of this study was to determine the independent predictors of DGA in this population. We performed a structured medical record review of 376 patients, ages ≥ 20 y, who had never been formally diagnosed with CD, presenting for an initial CD evaluation (ICD-9-CM 579.0) between January 2000 and December 2010 at two large Boston teaching hospitals. We collected data including demographic characteristics, medical history, history of CD serology before referral, and self-reported DGA. Predictors of DGA were determined using multivariable logistic regression. Mean age was 47 (SD = 17) years. We found that 41 patients (10.9%; 95% confidence interval [CI], 7.9-14.5) had avoided gluten at some time in their lives. Most patients had subjective abdominal complaints or bowel movement changes. History of CD seropositivity before referral was noted in 14%. Independent predictors of DGA (P < 0.05) were lactose intolerance (odds ratio [OR], 2.8; 95% CI, 1.1-7.5), food allergy (OR, 3.8; 95% CI, 1.04-13.7), and history of positive serology of less-specific CD markers before the referral (OR, 3.2; 95% CI, 1.3-7.9). Gluten avoidance is common in a clinic population of adults without prior CD diagnosis. The recognized predictors suggest that DGA may associate with conditions presenting with nonspecific gastrointestinal complaints and perhaps with the perceived benefits of DGA among patients with prior history of positive CD serology. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Characteristics of patients who avoid wheat and/or gluten in the absence of Celiac disease.

    PubMed

    Tavakkoli, Anna; Lewis, Suzanne K; Tennyson, Christina A; Lebwohl, Benjamin; Green, Peter H R

    2014-06-01

    Gastrointestinal symptoms that respond to the removal of wheat and/or gluten are becoming more common. Patients who avoid wheat and/or gluten (PWAWG) are a heterogeneous group and predominantly self-diagnosed prior to presenting for clinical evaluation. We characterized PWAWGs seen at a tertiary care referral center and compared them to patients with celiac disease (CD) and subjects in the National Health and Nutrition examination survey (NHANES). This was a cross-sectional study evaluating patients seen by four gastroenterologists at a CD referral center. Baseline characteristics, laboratory values, and medical comorbidities were compared to CD patients who presented at the same center and subjects enrolled in NHANES. Eighty-four PWAWGs were identified and compared to 585 CD patients and 2,686 NHANES patients. Thirty-two alternative diagnoses were made in 25 (30%) PWAWGs, including small intestinal bacterial overgrowth and fructose/lactose intolerance. When compared to patients with CD, PWAWGs had similar body mass index (BMI, 23.1 vs. 23.5, p = 0.54) and mean hemoglobin value (13.4 vs. 13.3, p = 0.6). When compared to male and female patients in NHANES, BMI, folate, and mean hemoglobin values were lower in PWAWGs. Both male and female PWAWGs had a lower prevalence of hypertension. While there are similarities between CD and PWAWGs that could possibly be due to shared HLA haplotypes or an effect of the gluten-free diet, alternative diagnoses are common in these patients. PWAWGs have a similar cardiovascular profile as CD patients in terms of lower BMI and lower prevalence of hypertension.

  14. Gluten-free diet normalizes mouth-to-cecum transit of a caloric meal in adult patients with celiac disease.

    PubMed

    Chiarioni, G; Bassotti, G; Germani, U; Battaglia, E; Brentegani, M T; Morelli, A; Vantini, I

    1997-10-01

    The mechanisms responsible for bowel disturbances in celiac disease are still relatively unknown. Recent reports suggested that small bowel motor abnormalities may be involved in this pathological condition; however, there are no studies addressing small bowel transit in celiac disease before and after a gluten-free diet. We studied the mouth-to-cecum transit time of a caloric liquid meal in a homogeneous group of celiac patients presenting with clinical and biochemical evidence of malabsorption and complaining of diarrhea. Sixteen patients were recruited and investigated by means of hydrogen breath test through ingestion of 20 g lactulose together with an enteral gluten-free diet formula. A urinary D-xylose test was also done in each patient. Both breath tests and D-xylose tests were carried out basally and after a period of gluten-free diet. Twenty healthy volunteers were recruited as a control group and underwent the same breath testing. At the time of the diagnosis, mouth-to-cecum transit time was significantly prolonged in celiacs with respect to controls (243 +/- 10 vs 117 +/- 6 min, P = 0.0001). The D-xylose test was also abnormal (average urinary concentration 2.8 +/- 0.25 g, normal values >4.5). No correlation was found in patients between mouth-to-cecum transit time and urinary D-xylose output (r = 0.22). After the gluten-free diet period, mouth-to-cecum transit time in celiacs was significantly reduced compared to prediet transit (134 +/- 8 vs 243 +/- 10 min, P = 0.0001) and did not show statistical difference when compared to that found in controls (P = 0.1). The D-xylose test reverted to normal in all but two subjects, who were found to be noncompliant with the diet. Mouth-to-cecum transit time is significantly prolonged in patients affected by untreated celiac disease when compared to healthy controls. This alteration might not be correlated to intestinal malabsorption, and the prolonged orocecal transit could be due to impaired small bowel function

  15. Treatment for Celiac Disease

    MedlinePlus

    ... Disease How do doctors treat celiac disease? A gluten-free diet Doctors treat celiac disease with a ... absorb nutrients from food into the bloodstream normally. Gluten-free diet and dermatitis herpetiformis If you have ...

  16. Proximal Limb Weakness in a Patient with Celiac Disease: Copper Deficiency, Gluten Sensitivity, or Both as the Underlying Cause?

    PubMed

    Avila, J David; Lacomis, David

    2016-01-01

    Celiac disease has been associated with several neurologic disorders which may result from micronutrient deficiencies, coexisting autoimmune conditions, or gluten sensitivity. Copper deficiency can produce multiple neurologic manifestations. Myeloneuropathy is the most common neurologic syndrome and it is often irreversible, despite copper replacement. We report the case of a 55-year-old man who presented with progressive proximal limb weakness and weight loss in the setting of untreated celiac disease without gastrointestinal symptoms. He had anemia, neutropenia, and severe hypocupremia. The pattern of weakness raised the suspicion that there was an underlying myopathy, although this was not confirmed by electrodiagnostic studies. Weakness and hematologic abnormalities resolved completely within 1 month of total parenteral nutrition with copper supplementation and a gluten-free diet. Myopathy can rarely occur in patients with celiac disease, but the mechanism is unclear. Pure proximal limb weakness has not been previously reported in copper deficiency. We propose that this may represent a novel manifestation of hypocupremia and recommend considering copper deficiency and gluten sensitivity in patients presenting with proximal limb weakness.

  17. Proximal Limb Weakness in a Patient with Celiac Disease: Copper Deficiency, Gluten Sensitivity, or Both as the Underlying Cause?

    PubMed Central

    Lacomis, David

    2016-01-01

    Celiac disease has been associated with several neurologic disorders which may result from micronutrient deficiencies, coexisting autoimmune conditions, or gluten sensitivity. Copper deficiency can produce multiple neurologic manifestations. Myeloneuropathy is the most common neurologic syndrome and it is often irreversible, despite copper replacement. We report the case of a 55-year-old man who presented with progressive proximal limb weakness and weight loss in the setting of untreated celiac disease without gastrointestinal symptoms. He had anemia, neutropenia, and severe hypocupremia. The pattern of weakness raised the suspicion that there was an underlying myopathy, although this was not confirmed by electrodiagnostic studies. Weakness and hematologic abnormalities resolved completely within 1 month of total parenteral nutrition with copper supplementation and a gluten-free diet. Myopathy can rarely occur in patients with celiac disease, but the mechanism is unclear. Pure proximal limb weakness has not been previously reported in copper deficiency. We propose that this may represent a novel manifestation of hypocupremia and recommend considering copper deficiency and gluten sensitivity in patients presenting with proximal limb weakness. PMID:27994896

  18. FTO Polymorphism rs9939609 Contributes to Weight Changes in Children With Celiac Disease on Gluten-Free Diet.

    PubMed

    Grandone, Anna; Marzuillo, Pierluigi; Cirillo, Grazia; Squitieri, Rosanna; Tolone, Salvatore; Miraglia del Giudice, Emanuele; Perrone, Laura; Tolone, Carlo

    2015-08-01

    Studies of adults and children with celiac disease have reported an increased risk of overweight during gluten-free diet (GFD). The fat mass and obesity-associated gene (FTO) variant rs9939609 has been associated with increased risk of developing obesity in children and adults. In our study, we analyzed the effect of this variant on weight gain in a cohort of 280 children with celiac disease on GFD. We found that after a mean follow-up time of 3.0 years on GFD, FTO polymorphism influenced significantly the mean change in body mass index z score (P = 0.01). We conclude that the FTO gene contributes to determine weight changes in children with celiac disease on GFD.

  19. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet.

    PubMed

    Pantaleoni, Stefano; Luchino, Massimo; Adriani, Alessandro; Pellicano, Rinaldo; Stradella, Davide; Ribaldone, Davide Giuseppe; Sapone, Nicoletta; Isaia, Gian Carlo; Di Stefano, Marco; Astegiano, Marco

    2014-01-01

    Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <-1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

  20. Lower Prevalence of Celiac Disease and Gluten-Related Disorders in Persons Living in Southern vs Northern Latitudes of the United States.

    PubMed

    Unalp-Arida, Aynur; Ruhl, Constance E; Choung, Rok Seon; Brantner, Tricia L; Murray, Joseph A

    2017-06-01

    The association between prevalence of celiac disease and geographic region is incompletely understood, but the occurrence of several autoimmune disorders has been found to vary along a North-South gradient. We examined geographic, demographic, and clinical factors associated with prevalence of celiac disease and gluten-free diet in the United States. In a population-based study, we analyzed data on gluten-related conditions from the National Health and Nutrition Examination Survey, from 2009 through 2014, on 22,277 participants 6 years and older. We identified persons with celiac disease based on results of serum tests for IgA against tissue transglutaminase and endomysium or on both a health care provider diagnosis and adherence to a gluten-free diet. Gluten avoidance without celiac disease was defined as adherence to a gluten-free diet without a diagnosis of celiac disease. We compared mean serum levels of biochemical and nutritional markers based on status of gluten-related conditions. We found 0.7% of participants to have celiac disease and 1.1% of participants to avoid gluten without celiac disease. Celiac disease was more common among individuals who lived at latitudes of 35°-39° North (odds ratio, 3.2; 95% confidence interval, 1.4-7.1) or at latitudes of 40° North or more (odds ratio, 5.4; 95% CI, 2.6-11.3) than individuals who lived at latitudes below 35° North, independent of race or ethnicity, socioeconomic status, and body mass index. Gluten avoidance without celiac disease was more common among individuals who lived at latitudes of 40° North or more, independent of demographic factors and body mass index. Participants with undiagnosed celiac disease (identified by positive results from serologic tests) had lower mean levels of vitamin B-12 and folate (data collected from 2009 through 2012) than persons without celiac disease. Participants with a health care provider diagnosis of celiac disease had a lower mean level of hemoglobin than persons

  1. Effects of Gluten Intake on Risk of Celiac Disease: A Case-Control Study on a Swedish Birth Cohort.

    PubMed

    Andrén Aronsson, Carin; Lee, Hye-Seung; Koletzko, Sibylle; Uusitalo, Ulla; Yang, Jimin; Virtanen, Suvi M; Liu, Edwin; Lernmark, Åke; Norris, Jill M; Agardh, Daniel

    2016-03-01

    Early nutrition may affect the risk of celiac disease. We investigated whether amount of gluten in diet until 2 years of age increases risk for celiac disease. We performed a 1-to-3 nested case-control study of 146 cases, resulting in 436 case-control pairs matched for sex, birth year, and HLA genotype generated from Swedish children at genetic risk for celiac disease. Newborns were annually screened for tissue transglutaminase autoantibodies (tTGA). If tested tTGA positive, time point of seroconversion was determined from frozen serum samples taken every 3 months. Celiac disease was confirmed by intestinal biopsies. Gluten intake was calculated from 3-day food records collected at ages 9, 12, 18 and 24 months. Odds ratios (OR) were calculated through conditional logistic regression. Breastfeeding duration (median, 32 wk) and age at first introduction to gluten (median, 22 wk) did not differ between cases and tTGA-negative controls. At the visit before tTGA seroconversion, cases reported a larger intake of gluten than controls (OR, 1.28; 95% confidence interval [CI], 1.13-1.46; P = .0002). More cases than controls were found in the upper third tertile (ie, >5.0 g/d) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P < .0001). This finding was similar in children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61-6.30; P = .001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08-4.62; P = .030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90-6.54; P = .079). The amount of gluten consumed until 2 years of age increases the risk of celiac disease at least 2-fold in genetically susceptible children. These findings may be taken into account for future infant feeding recommendations. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Identification of Pseudolysin (lasB) as an Aciduric Gluten-Degrading Enzyme with High Therapeutic Potential for Celiac Disease

    PubMed Central

    Wei, Guoxian; Tian, Na; Valery, Adriana C.; Zhong, Yi; Schuppan, Detlef; Helmerhorst, Eva J.

    2015-01-01

    OBJECTIVES Immunogenic gluten proteins implicated in celiac disease (CD) largely resist degradation by human digestive enzymes. Here we pursued the isolation of gluten-degrading organisms from human feces, aiming at bacteria that would digest gluten under acidic conditions, as prevails in the stomach. METHODS Bacteria with gluten-degrading activities were isolated using selective gluten agar plates at pH 4.0 and 7.0. Proteins in concentrated bacterial cell sonicates were separated by diethylaminoethanol chromatography. Enzyme activity was monitored with chromogenic substrates and gliadin zymography. Elimination of major immunogenic gluten epitopes was studied with R5 and G12 enzyme-linked immunosorbent assays. RESULTS Gliadin-degrading enzyme activities were observed for 43 fecal isolates, displaying activities in the ~150–200 and <50 kDa regions. The active strains were identified as Pseudomonas aeruginosa. Gliadin degradation in gel was observed from pH 2.0 to 7.0. Liquid chromatography–electrospray ionization–tandem mass spectrometry analysis identified the enzyme as pseudolysin (lasB), a metalloprotease belonging to the thermolysin (M4) family proteases. Its electrophoretic mobility in SDS–polyacrylamide gel electrophoresis and gliadin zymogram gels was similar to that of a commercial lasB preparation, with tendency of oligomerization. Pseudolysin eliminated epitopes recognized by the R5 antibody, while those detected by the G12 antibody remained intact, despite destruction of the nearby major T-cell epitope QPQLPY. CONCLUSIONS Pseudolysin was identified as an enzyme cleaving gluten effectively at extremely low as well as near-neutral pH values. The potential to degrade gluten during gastric transport opens possibilities for its application as a novel therapeutic agent for the treatment of CD. PMID:25895519

  3. Gastrointestinal Symptoms in Celiac Disease Patients on a Long-Term Gluten-Free Diet

    PubMed Central

    Laurikka, Pilvi; Salmi, Teea; Collin, Pekka; Huhtala, Heini; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle

    2016-01-01

    Experience suggests that many celiac patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD). We investigated the prevalence and severity of these symptoms in patients with variable duration of GFD. Altogether, 856 patients were classified into untreated (n = 128), short-term GFD (1–2 years, n = 93) and long-term GFD (≥3 years, n = 635) groups. Analyses were made of clinical and histological data and dietary adherence. Symptoms were evaluated by the validated GSRS questionnaire. One-hundred-sixty healthy subjects comprised the control group. Further, the severity of symptoms was compared with that in peptic ulcer, reflux disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Altogether, 93% of the short-term and 94% of the long-term treated patients had a strict GFD and recovered mucosa. Untreated patients had more diarrhea, indigestion and abdominal pain than those on GFD and controls. There were no differences in symptoms between the short- and long-term GFD groups, but both yielded poorer GSRS total score than controls (p = 0.03 and p = 0.05, respectively). Furthermore, patients treated 1–2 years had more diarrhea (p = 0.03) and those treated >10 years more reflux (p = 0.04) than controls. Long-term treated celiac patients showed relatively mild symptoms compared with other gastrointestinal diseases. Based on our results, good response to GFD sustained in long-term follow-up, but not all patients reach the level of healthy individuals. PMID:27428994

  4. Duodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity.

    PubMed

    Caminero, Alberto; Galipeau, Heather J; McCarville, Justin L; Johnston, Chad W; Bernier, Steve P; Russell, Amy K; Jury, Jennifer; Herran, Alexandra R; Casqueiro, Javier; Tye-Din, Jason A; Surette, Michael G; Magarvey, Nathan A; Schuppan, Detlef; Verdu, Elena F

    2016-10-01

    Partially degraded gluten peptides from cereals trigger celiac disease (CD), an autoimmune enteropathy occurring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CD, and additional environmental factors related to unfavorable alterations in the microbiota have been proposed. We investigated gluten metabolism by opportunistic pathogens and commensal duodenal bacteria and characterized the capacity of the produced peptides to activate gluten-specific T-cells from CD patients. We colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CD patients or healthy controls, selected for their in vitro gluten-degrading capacity. After gluten gavage, gliadin amount and proteolytic activities were measured in intestinal contents. Peptides produced by bacteria used in mouse colonizations from the immunogenic 33-mer gluten peptide were characterized by liquid chromatography tandem mass spectrometry and their immunogenic potential was evaluated using peripheral blood mononuclear cells from celiac patients after receiving a 3-day gluten challenge. Bacterial colonizations produced distinct gluten-degradation patterns in the mouse small intestine. Pseudomonas aeruginosa, an opportunistic pathogen from CD patients, exhibited elastase activity and produced peptides that better translocated the mouse intestinal barrier. P aeruginosa-modified gluten peptides activated gluten-specific T-cells from CD patients. In contrast, Lactobacillus spp. from the duodenum of non-CD controls degraded gluten peptides produced by human and P aeruginosa proteases, reducing their immunogenicity. Small intestinal bacteria exhibit distinct gluten metabolic patterns in vivo, increasing or reducing gluten peptide immunogenicity. This microbe-gluten-host interaction may modulate autoimmune risk in genetically susceptible persons and may underlie the reported association of dysbiosis and CD. Copyright © 2016 AGA Institute

  5. [Specific features of rehabilitation in patients with gluten-sensitivity celiac disease].

    PubMed

    Sabel'nikova, E A; Krums, L M; Parfenov, A I; Vorob'eva, N N; Gudkova, R B

    2013-01-01

    To elaborate recommendations for rehabilitation of patients with gluten-sensitivity celiac disease (GCD) on the basis of a long-term follow-up. Eighty-seven patients with GCD were followed up for as long as 31 years. Of those, 72.4% of the patients kept strictly to their gluten-free diet (GFD) throughout the follow-up; 9.2% did not follow the diet periodically; and 18.4% did not at all. The sera from 71 patients were tested for IgA and IgG anti-gliadin antibodies (AGAb) and anti-tissue transglutaminase antibodies (ATTGAb) at as long as 19-year follow-up. AGAb and ATTGAb were estimated by enzyme immunoassay (IMMCO Diagnostics). All the patients underwent endoscopic and histological examinations of the small bowel mucosa (SBM). To support the validity of keeping to the GFD, the time course of clinical, laboratory, and morphological changes were analyzed in 63 and 24 GFD followers and non-followers, respectively. The GFD non-followers were more frequently found to have diarrheic syndrome, symptoms of malabsorption syndrome, lower serum concentrations of hemoglobin, total protein, iron, and calcium; no SBM structural recovery was seen in any patient. When the GFD was long adhered to, there was also a reduction in detection rates and AGAb and ATTGAb concentrations. The adherence to the GFD was ascertained to contribute to fuller rehabilitation in the patients. However, even the patients who had strictly kept to their GFD showed periods of an exacerbation and incomplete SBM structural recovery. Therefore, the rehabilitation system for patients with GCD must involve diagnostic, therapeutic, and organizational measures that promote not only rapid clinical recovery, but also better quality of life in these patients.

  6. Intakes of nutrients in Italian children with celiac disease and the role of commercially available gluten-free products.

    PubMed

    Zuccotti, G; Fabiano, V; Dilillo, D; Picca, M; Cravidi, C; Brambilla, P

    2013-10-01

    Celiac disease (CD) is a chronic gluten-sensitive enteropathy. Life-long gluten-free diet (GFD) is the only therapeutic option; however, it may contribute to the consumption of an unbalanced diet. The present study aimed to evaluate the dietary intake of CD affected children on a GFD and compare it with non-celiac children and with Italian nutritional intakes recommendations, as well as evaluate the contribution of commercially available gluten-free products (GFPs). Eighteen celiac children, median age 7.6 years, median GFD duration 4.2 years, and 18 non-celiac controls, were enrolled in a cross-sectional age-matched study. Dietary intakes of both groups were collected using a food frequency questionnaire and a 24-hour dietary recall. Nutritional intakes were compared between the group and controls and with Italian dietary reference values. The contribution of GFPs to energy and macronutrient intakes was evaluated. Median energy intake was significantly higher in CD patients than in controls (8961.8 and 5761.0 kJ day(-1); P < 0.001). CD subjects showed higher carbohydrate intakes and lower fat intakes compared to controls. Protein-derived energy did not differ. By contrast to control subjects, energy derived from carbohydrate intakes in CD children met the Italian recommendations. Both children groups showed higher protein and fat intakes than recommended in Italy. GFPs consumption accounted for 36.3% of daily total energy intake. Intakes of simple sugars, fats and protein exceeded the National recommendations for health. Children with CD had significantly higher energy intakes than controls, although body mass index was comparable across the groups. Lack of nutritional information for GFPs prevented complete dietary analysis of subfractions of fat and micronutrient intakes. This aspect need to be addressed if studies in this field are to be meaningful in the future. © 2012 The Authors Journal of Human Nutrition and Dietetics © 2012 The British Dietetic

  7. Co-localization of gluten consumption and HLA-DQ2 and -DQ8 genotypes, a clue to the history of celiac disease.

    PubMed

    Lionetti, Elena; Catassi, Carlo

    2014-12-01

    Celiac disease is an immune-mediated disorder triggered by gluten in genetically susceptible persons. Despite its detrimental effects on human health, it has not disappeared over time. The current evolutionary theory is that celiac disease is more common in areas reached later by agricultural revolution than in countries that started consumption of wheat earlier, due to negative selection caused by celiac disease. We reviewed data on worldwide prevalence of celiac disease, wheat consumption, and frequencies of HLA-celiac-disease-predisposing-genotypes to investigate their mutual relationship. Studies assessing prevalence of celiac disease were identified through a MEDLINE search. Wheat consumption and frequencies of HLA-DQ2-DQ8 were obtained from Food and Agriculture Organization of the United Nations and allelefrequencies.net database. Correlations between celiac disease, wheat consumption, and HLA were analyzed by linear regression. We observed a significant correlation between wheat consumption and HLA DQ2 (p=0.01) and the sum of DQ2 and DQ8 (p=0.01) frequencies. Wheat consumption and HLA-DQ2 tend to co-localize in different continents. The correlation between the prevalence of celiac disease and either DQ2 and/or DQ8, or the product of DQ2+DQ8*wheat consumption was not statistically significant. Co-localization of gluten consumption and HLA-celiac-disease-predisposing-genotypes can be explained by positive selection of HLA-DQ2 genes in wheat-consuming areas, and "demic diffusion" of Middle East farmers into Europe.

  8. Decrease in lactobacilli in the intestinal microbiota of celiac children with a gluten-free diet, and selection of potentially probiotic strains.

    PubMed

    Lorenzo Pisarello, María J; Vintiñi, Elisa O; González, Silvia N; Pagani, Florencia; Medina, Marcela S

    2015-01-01

    The intestinal microbiota would be implicated in pathology associated with celiac disease caused by an abnormal immune system reaction against gluten present in cereal grains. The objectives of this work were to detect through basic methods the changes in the composition of the most common genera of bacteria from the intestinal microbiota of symptom-free celiac disease children with a gluten-free diet compared with healthy children from Tucumán and to select lactobacilli (Lb) strains with probiotic potential from the feces of healthy children. Results demonstrated that the feces of celiac children with a gluten-free diet showed significantly lower counts of Lb (P < 0.05) compared with healthy children, while enterobacteria tended to increase in celiac children. On the basis of these results, isolation of some Lb from the feces of healthy children was carried out. Thus, 5 Lb strains were selected because of their high resistance percentages to gastrointestinal tract conditions. In addition, their autoaggregation and hydrophobicity properties were evaluated: Lactobacillus rhamnosus (LC4) showed the highest percentage of autoaggregation while Lactobacillus paracasei (LC9) showed high hydrophobicity. Based on these results, LC4 and LC9 were selected, and their use as potential probiotic strains to improve signs and symptoms associated with celiac disease is discussed. This is the first study performed in Argentina concerning the relationship between intestinal microbiota and celiac disease in celiac children with a gluten-free diet. In addition, the development of a probiotic food addressed towards celiac patients and designed with Lb isolated from the feces of healthy children from our province represents a promising alternative to improve the quality of life of celiac patients.

  9. Assessing the proposed association between DED and gluten-free diet introduction in celiac children.

    PubMed

    de Queiroz, Alexandra Mussolino; Arid, Juliana; de Carvalho, Fabrício Kitazono; da Silva, Raquel Assed Bezerra; Küchler, Erika Calvano; Sawamura, Regina; da Silva, Lea Assed Bezerra; Nelson-Filho, Paulo

    2017-07-01

    A strong association between celiac disease (CD) and dental enamel defects (DEDs) have been extensively reported, however, the nature of this relationship is still unclear. The aim of this study was to evaluate DEDs phenotype in CD individuals according to the time they were introduced to a gluten-free diet (GFD). Forty-five CD individuals were examined by a pediatric dentist. DEDs were classified according to the type of affected teeth. CD individuals were classified into two groups (with or without DEDs) and the differences between these groups were tested using chi-square or Fisher´s exact tests and t-test to compare differences between means. The Pearson coefficient test was used to evaluate the degree of the correlation between the age of GFD introduction and number of affected teeth. Individuals with MIH were introduced earlier to the GFD (p = 0.038). An association was also observed for molar DED (p = 0.013). In conclusion, our study suggested an association between a specific type of DED and the time that CD individuals were introduced to a GFD. © 2017 Special Care Dentistry Association and Wiley Periodicals, Inc.

  10. Gluten-free is not enough--perception and suggestions of celiac consumers.

    PubMed

    do Nascimento, Amanda Bagolin; Fiates, Giovanna Medeiros Rataichesck; dos Anjos, Adilson; Teixeira, Evanilda

    2014-06-01

    The present study investigated the perceptions of individuals with celiac disease about gluten-free (GF) products, their consumer behavior and which product is the most desired. A survey was used to collect information. Descriptive analysis, χ² tests and Multiple Logistic Regressions were conducted. Ninety-one questionnaires were analyzed. Limited variety and availability, the high price of products and the social restrictions imposed by the diet were the factors that caused the most dissatisfaction and difficulty. A total of 71% of the participants confirmed having moderate to high difficulty finding GF products. The logistic regression identified a significant relationship between dissatisfaction, texture and variety (p < 0.05) and between variety and difficulty of finding GF products (p < 0.05). The sensory characteristics were the most important variables considered for actual purchases. Bread was the most desired product. The participants were dissatisfaction with GF products. The desire for bread with better sensory characteristics reinforces the challenge to develop higher quality baking products.

  11. Resolution of metabolic syndrome after following a gluten free diet in an adult woman diagnosed with celiac disease

    PubMed Central

    García-Manzanares, Álvaro; Lucendo, Alfredo J; González-Castillo, Sonia; Moreno-Fernández, Jesús

    2011-01-01

    Adult celiac disease (CD) presents with very diverse symptoms that are clearly different from those typically seen in pediatric patients, including ferropenic anemia, dyspepsia, endocrine alterations and elevated transaminase concentration. We present the case of a 51-year-old overweight woman with altered basal blood glucose, hypercholesterolemia, hypertriglyceridemia and persisting elevated transaminase levels, who showed all the symptoms for a diagnosis of metabolic syndrome. Because she presented iron deficiency anemia, she was referred to the gastroenterology department and subsequently diagnosed with celiac disease after duodenal biopsies and detection of a compatible HLA haplotype. Gluten-free diet (GFD) was prescribed and after 6 mo the patient showed resolution of laboratory abnormalities (including recovering anemia and iron reserves, normalization of altered lipid and liver function parameters and decrease of glucose blood levels). No changes in weight or waist circumference were observed and no significant changes in diet were documented apart from the GFD. The present case study is the first reported description of an association between CD and metabolic syndrome, and invites investigation of the metabolic changes induced by gluten in celiac patients. PMID:21860836

  12. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study.

    PubMed

    Lebwohl, Benjamin; Cao, Yin; Zong, Geng; Hu, Frank B; Green, Peter H R; Neugut, Alfred I; Rimm, Eric B; Sampson, Laura; Dougherty, Lauren W; Giovannucci, Edward; Willett, Walter C; Sun, Qi; Chan, Andrew T

    2017-05-02

    avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten-free diets among people without celiac disease should not be encouraged. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Quality of Life in Type 1 Diabetes and Celiac Disease: Role of the Gluten-Free Diet.

    PubMed

    Pham-Short, Anna; Donaghue, Kim C; Ambler, Geoffrey; Garnett, Sarah; Craig, Maria E

    2016-12-01

    To evaluate quality of life (QoL) and glycemic control in youth with type 1 diabetes (T1D) and celiac disease vs T1D only. We hypothesized that QoL scores would be lower in youth with T1D and celiac disease and those nonadherent to the gluten-free diet (GFD). This case control study included 35 youth with T1D and 35 with T1D  and  celiac disease matched for age, sex, diabetes duration, and hemoglobin A1c level. QoL was assessed in participants and parents using the Pediatric Quality of Life Inventory Generic Core Scale, Pediatric Quality of Life Inventory Diabetes Module. and the General Well-Being Scale; youth with T1D and celiac disease also completed the celiac disease-specific DUX questionnaire and parents completed the Pediatric Quality of Life Inventory Family Impact Scale. Questionnaires were scored from 0 to 100; higher scores indicate better QoL or well-being. Scores were compared between T1D vs T1D with celiac disease, with subgroup analysis by GFD adherence vs nonadherence and therapy (continuous subcutaneous insulin infusion vs multiple daily injections). Youth with T1D  and celiac disease reported similar generic and diabetes-specific QoL to T1D only. GFD nonadherent vs adherent youth reported lower diabetes-specific QoL (mean score 58 vs 75, P = .003) and lower general well-being (57 vs 76, P = .02), as did their parents (50 vs 72, P = .006), and hemoglobin A1c was higher (9.6% vs 8.0%, P = .02). Youth with T1D  and  celiac disease using continuous subcutaneous insulin infusion vs multiple daily injections had similar generic and diabetes-specific QoL and A1C (8.6 vs 8.2%, P = .44), but were less happy having to follow a lifelong diet (59 vs 29, P = .007). Youth with T1D  and celiac disease who do not adhere to the GFD have lower QoL and worse glycemic control. Novel strategies are required to understand and improve adherence in those with both conditions. Copyright © 2016 Elsevier Inc. All rights

  14. Effects of Gluten-Free Diet on Quality of Life and Depression in Children With Celiac Disease.

    PubMed

    Simsek, Seref; Baysoy, Gokhan; Gencoglan, Salih; Uluca, Unal

    2015-09-01

    The aim of this study was to investigate the level of depression and quality of life in children with celiac disease (CD). In addition, it aimed to examine the relations of depression level and life quality with adherence to a gluten-free diet (GFD). Twenty-five children with CD and 25 healthy controls were included. The Depression Scale for Children and the General Purpose Health-Related Quality of Life Scale for Children were performed on patients before and after receiving recommendations to follow a GFD. No significant differences were found in the depression scores between the patients and the control subjects (P > 0.05). In contrast, total scores and scores of the emotional well-being subscale of the measure of Quality of Life Scale for Children were significantly lower in patients with CD compared with the control group (P < 0.05). No significant improvements were observed in depression or life quality scores of the total subsample of celiac patients, all of whom received a recommendation to follow a GFD (P > 0.05). Significant decrease was observed in the depression scores, however, of celiac patients who were able to actually adhere to the GFD compared with nonadherent patients. CD negatively affected quality of life in children. Adherence to GFD was associated with reduction in depression symptoms. Improving the adherence of celiac patients to a GFD may have a favorable effect on their depression symptoms.

  15. Dietary gluten triggers concomitant activation of CD4+ and CD8+ αβ T cells and γδ T cells in celiac disease

    PubMed Central

    Han, Arnold; Newell, Evan W.; Glanville, Jacob; Fernandez-Becker, Nielsen; Khosla, Chaitan; Chien, Yueh-hsiu; Davis, Mark M.

    2013-01-01

    Celiac disease is an intestinal autoimmune disease driven by dietary gluten and gluten-specific CD4+ T-cell responses. In celiac patients on a gluten-free diet, exposure to gluten induces the appearance of gluten-specific CD4+ T cells with gut-homing potential in the peripheral blood. Here we show that gluten exposure also induces the appearance of activated, gut-homing CD8+ αβ and γδ T cells in the peripheral blood. Single-cell T-cell receptor sequence analysis indicates that both of these cell populations have highly focused T-cell receptor repertoires, indicating that their induction is antigen-driven. These results reveal a previously unappreciated role of antigen in the induction of CD8+ αβ and γδ T cells in celiac disease and demonstrate a coordinated response by all three of the major types of T cells. More broadly, these responses may parallel adaptive immune responses to viral pathogens and other systemic autoimmune diseases. PMID:23878218

  16. Between Celiac Disease and Irritable Bowel Syndrome: The “No Man’s Land” of Gluten Sensitivity

    PubMed Central

    Verdu, Elena F.; Armstrong, David; Murray, Joseph A.

    2012-01-01

    The repertoire of gastrointestinal (GI) symptoms is finite; however, the etiologies and mechanisms underlying symptom generation and perception are diverse and, in many cases, unknown. This review examines the clinical and experimental evidence exploring the putative relationship between gluten sensitivity (GS) and the generation of GI symptoms. It explores the hypothesis that, in a proportion of patients, GS causes functional bowel disorder (FBD)-like symptoms. We propose a model for investigating and understanding the induction of GI symptoms and dysfunction by gluten in FBD and organic disease. We hypothesize that, even in the absence of fully developed celiac disease, gluten can induce symptoms similar to FBD. We discuss the hypothesis that GS and post-infectious irritable bowel syndrome (IBS) provide two triggers that can explain at least part of the spectrum that constitutes IBS, further advancing an understanding of the role of mucosal responses to luminal factors in FBDs. We propose that the animal model of GS in human leukocyte antigen (HLA)-DQ8 mice allows investigation of mucosal pathophysiological changes that occur before the onset of full-blown inflammation in a GS host. A better understanding of how gluten can cause symptoms in sensitive individuals will illuminate the interaction between host genotype, diet, and intestinal microbiota in generating one of the most common GI conditions. PMID:19455131

  17. Highly Efficient Gluten Degradation by Lactobacilli and Fungal Proteases during Food Processing: New Perspectives for Celiac Disease▿

    PubMed Central

    Rizzello, Carlo G.; De Angelis, Maria; Di Cagno, Raffaella; Camarca, Alessandra; Silano, Marco; Losito, Ilario; De Vincenzi, Massimo; De Bari, Maria D.; Palmisano, Francesco; Maurano, Francesco; Gianfrani, Carmen; Gobbetti, Marco

    2007-01-01

    Presently, the only effective treatment for celiac disease is a life-long gluten-free diet. In this work, we used a new mixture of selected sourdough lactobacilli and fungal proteases to eliminate the toxicity of wheat flour during long-time fermentation. Immunological (R5 antibody-based sandwich and competitive enzyme-linked immunosorbent assay [ELISA] and R5 antibody-based Western blot), two-dimensional electrophoresis, and mass spectrometry (matrix-assisted laser desorption ionization-time of flight, strong-cation-exchange-liquid chromatography/capillary liquid chromatography-electrospray ionization-quadrupole-time of flight [SCX-LC/CapLC-ESI-Q-TOF], and high-pressure liquid chromatography-electrospray ionization-ion trap mass spectrometry) analyses were used to determine the gluten concentration. Assays based on the proliferation of peripheral blood mononuclear cells (PBMCs) and gamma interferon production by PBMCs and intestinal T-cell lines (iTCLs) from 12 celiac disease patients were used to determine the protein toxicity of the pepsin-trypsin digests from fermented wheat dough (sourdough). As determined by R5-based sandwich and competitive ELISAs, the residual concentration of gluten in sourdough was 12 ppm. Albumins, globulins, and gliadins were completely hydrolyzed, while ca. 20% of glutenins persisted. Low-molecular-weight epitopes were not detectable by SCX-LC/CapLC-ESI-Q-TOF mass spectrometry and R5-based Western blot analyses. The kinetics of the hydrolysis of the 33-mer by lactobacilli were highly efficient. All proteins extracted from sourdough activated PBMCs and induced gamma interferon production at levels comparable to the negative control. None of the iTCLs demonstrated immunoreactivity towards pepsin-trypsin digests. Bread making was standardized to show the suitability of the detoxified wheat flour. Food processing by selected sourdough lactobacilli and fungal proteases may be considered an efficient approach to eliminate gluten toxicity

  18. Highly efficient gluten degradation by lactobacilli and fungal proteases during food processing: new perspectives for celiac disease.

    PubMed

    Rizzello, Carlo G; De Angelis, Maria; Di Cagno, Raffaella; Camarca, Alessandra; Silano, Marco; Losito, Ilario; De Vincenzi, Massimo; De Bari, Maria D; Palmisano, Francesco; Maurano, Francesco; Gianfrani, Carmen; Gobbetti, Marco

    2007-07-01

    Presently, the only effective treatment for celiac disease is a life-long gluten-free diet. In this work, we used a new mixture of selected sourdough lactobacilli and fungal proteases to eliminate the toxicity of wheat flour during long-time fermentation. Immunological (R5 antibody-based sandwich and competitive enzyme-linked immunosorbent assay [ELISA] and R5 antibody-based Western blot), two-dimensional electrophoresis, and mass spectrometry (matrix-assisted laser desorption ionization-time of flight, strong-cation-exchange-liquid chromatography/capillary liquid chromatography-electrospray ionization-quadrupole-time of flight [SCX-LC/CapLC-ESI-Q-TOF], and high-pressure liquid chromatography-electrospray ionization-ion trap mass spectrometry) analyses were used to determine the gluten concentration. Assays based on the proliferation of peripheral blood mononuclear cells (PBMCs) and gamma interferon production by PBMCs and intestinal T-cell lines (iTCLs) from 12 celiac disease patients were used to determine the protein toxicity of the pepsin-trypsin digests from fermented wheat dough (sourdough). As determined by R5-based sandwich and competitive ELISAs, the residual concentration of gluten in sourdough was 12 ppm. Albumins, globulins, and gliadins were completely hydrolyzed, while ca. 20% of glutenins persisted. Low-molecular-weight epitopes were not detectable by SCX-LC/CapLC-ESI-Q-TOF mass spectrometry and R5-based Western blot analyses. The kinetics of the hydrolysis of the 33-mer by lactobacilli were highly efficient. All proteins extracted from sourdough activated PBMCs and induced gamma interferon production at levels comparable to the negative control. None of the iTCLs demonstrated immunoreactivity towards pepsin-trypsin digests. Bread making was standardized to show the suitability of the detoxified wheat flour. Food processing by selected sourdough lactobacilli and fungal proteases may be considered an efficient approach to eliminate gluten toxicity.

  19. The effects of modified versus unmodified wheat gluten administration in patients with celiac disease.

    PubMed

    Marino, Mariacatia; Casale, Rossella; Borghini, Raffaele; Di Nardi, Sara; Donato, Giuseppe; Angeloni, Antonio; Moscaritolo, Salvatore; Grasso, Lorenza; Mazzarella, Giuseppe; Di Tola, Marco; Rossi, Mauro; Picarelli, Antonio

    2017-03-23

    Celiac disease (CD) treatment requires a gluten-free diet (GFD), although alternative approaches have been proposed. Modification of gliadin peptides using microbial transglutaminase (mTG) inhibits their ability to induce immune response in vitro. Our aim was to evaluate the safety of mTG-modified wheat flour ingestion in CD patients. Twenty-one CD patients in remission were randomized to receive mTG-modified (n=11) or unmodified (n=10) wheat flour rusks, in double-blind fashion. Monthly, patients completed a symptom questionnaire. Serum anti-tTG, EMA and creatinine levels were monitored. At baseline and after 90days, serum anti-actin antibodies (AAA) were measured and upper endoscopy was performed. Data were analyzed by non-parametric tests. 7/11 patients eating modified rusks and 7/10 patients receiving unmodified rusks completed the study. At baseline, all patients showed negative serum anti-tTG and EMA results. At the end, 2/7 (28.6%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented positive serum anti-tTG and EMA results. Creatinine results were unmodified. Moreover, 1/7 (14.3%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented villous atrophy. In patients who received unmodified rusks, the AAA levels increased significantly and duodenal anti-tTG levels appeared higher than those measured in patients who ate modified rusks. Abdominal swelling, bloating and nausea were more severe in patients ingesting unmodified rusks than those taking modified rusks. Our results may support larger clinical trials to confirm the enzymatic treatment of wheat flour as an alternative to GFD. Clinicaltrials.gov registration no: NCT02472119.

  20. Can an Increase in Celiac Disease Be Attributed to an Increase in the Gluten Content of Wheat as a Consequence of Wheat Breeding?

    PubMed Central

    2013-01-01

    In response to the suggestion that an increase in the incidence of celiac disease might be attributable to an increase in the gluten content of wheat resulting from wheat breeding, a survey of data from the 20th and 21st centuries for the United States was carried out. The results do not support the likelihood that wheat breeding has increased the protein content (proportional to gluten content) of wheat in the United States. Possible roles for changes in the per capita consumption of wheat flour and the use of vital gluten as a food additive are discussed. PMID:23311690

  1. Can an increase in celiac disease be attributed to an increase in the gluten content of wheat as a consequence of wheat breeding?

    PubMed

    Kasarda, Donald D

    2013-02-13

    In response to the suggestion that an increase in the incidence of celiac disease might be attributable to an increase in the gluten content of wheat resulting from wheat breeding, a survey of data from the 20th and 21st centuries for the United States was carried out. The results do not support the likelihood that wheat breeding has increased the protein content (proportional to gluten content) of wheat in the United States. Possible roles for changes in the per capita consumption of wheat flour and the use of vital gluten as a food additive are discussed.

  2. Treatment of both native and deamidated gluten peptides with an endo-peptidase from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T cells from either children or adults with celiac disease.

    PubMed

    Toft-Hansen, Henrik; Rasmussen, Karina S; Staal, Anne; Roggen, Erwin L; Sollid, Ludvig M; Lillevang, Søren T; Barington, Torben; Husby, Steffen

    2014-08-01

    Celiac disease (CD) is characterized by an inappropriate immunological reaction against gluten driven by gluten-specific CD4+ T cells. We screened 25 proteases and tested 10 for their potential to degrade gluten in vitro. Five proteases were further tested for their ability to prevent the proliferative response by a gluten-specific CD4+ T cell clone and seven gluten-reactive T cell lines to protease-digested gluten peptides. A proline-specific endo-peptidase from Aspergillus niger (AnP2) was particularly efficient at diminishing proliferation after stimulation with cleaved antigen, and could completely block the response against both native and deamidated gluten peptides. We found that AnP2 was efficient down to a 1:64 protease:substrate ratio (w:w). When AnP2 was tested in assays using seven gluten-reactive T cell lines from individual CD patients (three adults and four children), the response to gluten was diminished in all cases. Our study indicates a therapeutic benefit of AnP2 to CD patients.

  3. Can an increase in celiac disease be attributed to an increase in the gluten content of wheat as a consequence of wheat breading? A perspective

    USDA-ARS?s Scientific Manuscript database

    In order to assess the possibility that wheat breeding has been responsible for an increase in the gluten content of U.S. wheat cultivars and thereby responsible for an increase in the incidence of celiac disease, the available data from the 20th century has been analyzed. Although much of the infor...

  4. Gynecologic and obstetric findings related to nutritional status and adherence to a gluten-free diet in Brazilian patients with celiac disease.

    PubMed

    Kotze, L M S

    2004-08-01

    This study shows a broad analysis of gynaecological and obstetrical disturbances in patients with celiac disease in relation to their nutritional status and adherence to a gluten-free diet. Seventy-six adult celiac patients were analyzed according to nutritional status and 18 children/adolescents to gluten-free diet adherence. As controls, 84 adults and 22 adolescents with irritable bowel syndrome were used The significant findings were observed as follow: adult celiac patients, irrespective of the nutritional status, were younger than controls, presented delayed menarche, secondary amenorrhea, a higher percentage of spontaneous abortions, anemia and hypoalbuminemia. No differences were observed regarding the number of pregnancies, age at menopause and duration of the reproductive period. After treatment, patients presented with normal pregnancies and one patient presented spontaneous abortion. The adolescents who were not adherent to gluten-free diet presented delayed menarche and secondary amenorrhea. In conclusion, gluten per se could explain the disturbances and malnutrition would worsen the disease in a consequent vicious cycle. Therefore, celiac disease should be included in the screening of reproductive disorders.

  5. Enzyme-linked immunosorbent assay gliadin assessment in processed food products available for persons with celiac disease: a feasibility study for developing a gluten-free food database.

    PubMed

    Agakidis, Charalampos; Karagiozoglou-Lampoudi, Thomais; Kalaitsidou, Marina; Papadopoulos, Theodoros; Savvidou, Afroditi; Daskalou, Efstratia; Dimitrios, Triantafyllou

    2011-12-01

    Inappropriate food labeling and unwillingness of food companies to officially register their own gluten-free products in the Greek National Food Intolerance Database (NFID) result in a limited range of processed food products available for persons with celiac disease (CDP). The objective of the study was to evaluate the feasibility of developing a gluten-free food product database based on the assessment of the gluten content in processed foods available for CDP. Gluten was assessed in 41 processed food products available for CDP. Group A consisted of 26 products for CDP included in the NFID, and group B contained 15 food products for CDP not registered in the NFID but listed in the safe lists of the local Celiac Association (CA). High-sensitivity ω-gliadin enzyme-linked immunosorbent assay (ELISA) was used for analysis. Gluten was lower than 20 ppm in 37 of 41 analyzed products (90.2%): in 24 of 26 (92.3%) products in group A and in 13 of 15 (86.7%) products in group B (P = .61). No significant difference was found between the 2 groups regarding gluten content. No product in either group contained gluten in excess of 100 ppm. Most of the analyzed products included in the Greek NFID or listed in the lists of the local CA, even those not officially labeled "gluten free," can be safely consumed by CDP. The use of commercially available ω-gliadin ELISA is able to identify those products that contain inappropriate levels of gluten, making feasible it to develop an integrated gluten-free processed food database.

  6. The Shutdown of Celiac Disease-Related Gliadin Epitopes in Bread Wheat by RNAi Provides Flours with Increased Stability and Better Tolerance to Over-Mixing

    PubMed Central

    Gil-Humanes, Javier; Pistón, Fernando; Barro, Francisco; Rosell, Cristina M.

    2014-01-01

    Celiac disease is a food-sensitive enteropathy triggered by the ingestion of wheat gluten proteins and related proteins from barley, rye, and some varieties of oat. There are no interventional therapies and the only solution is a lifelong gluten-free diet. The down-regulation of gliadins by RNAi provides wheat lines with all the gliadin fractions strongly down-regulated (low-gliadin). The technological properties of doughs prepared from the low-gliadin lines indicated a general weakening effect, although some of the lines displayed similar properties to that of the wild-type lines. In contrast, the stability was increased significantly in some of the transgenic lines, indicating better tolerance to over-mixing. Results reported here are the first analyses of the mixing and bread-making quality of the wheat lines with all gliadin fractions strongly down-regulated. Flour from these lines may be an important breakthrough in the development of new products for the celiac community. These lines might be used directly or blended with other non-toxic cereals, as raw material for developing food products that can be safely tolerated by CD patients and others with gluten intolerance or gluten sensitivity, incrementing the range of available food products and enhancing their diet. PMID:24633046

  7. Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet.

    PubMed

    Zanini, Barbara; Marullo, Monica; Villanacci, Vincenzo; Salemme, Marianna; Lanzarotto, Francesco; Ricci, Chiara; Lanzini, Alberto

    2016-08-26

    The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12-18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696].

  8. Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet

    PubMed Central

    Zanini, Barbara; Marullo, Monica; Villanacci, Vincenzo; Salemme, Marianna; Lanzarotto, Francesco; Ricci, Chiara; Lanzini, Alberto

    2016-01-01

    The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696] PMID:27571100

  9. Anti-transglutaminase 6 Antibody Development in Children With Celiac Disease Correlates With Duration of Gluten Exposure.

    PubMed

    De Leo, Luigina; Aeschlimann, Daniel; Hadjivassiliou, Marios; Aeschlimann, Pascale; Salce, Nicola; Vatta, Serena; Ziberna, Fabiana; Cozzi, Giorgio; Martelossi, Stefano; Ventura, Alessandro; Not, Tarcisio

    2017-05-24

    Antibodies against transglutaminase 6 (anti-TG6) have been implicated in neurological manifestations in adult patients with genetic-gluten intolerance and it is unclear whether autoimmunity to TG6 develops following prolonged gluten exposure. We measured the anti-TG6 in children with celiac disease (CD) at the diagnosis time to establish a correlation between these autoantibodies and the duration of gluten exposure. We investigated a correlation between anti-TG6 and the presence of neurological disorders. Anti-TG6 (IgA/IgG) were measured by ELISA in sera of children with biopsy-proven CD and of children suffering from gastrointestinal disorders. CD-patients positive for anti-TG6 were retested after 2 years of gluten-free diet (GFD). We analyzed the sera of 274 CD-children and of 121 controls. Anti-TG6 were detected in 68/274 (25%) CD-patients and in 19/121 (16%) controls, with significant difference between the two groups (p = 0.04). None of the CD-patients and of the controls testing positive for anti-TG6 were suffering from neurological disorders. Eleven/18 (61%) CD-patients with other autoimmune diseases were positive for anti-TG6. In CD-patients a significant correlation between the gluten exposure before the CD-diagnosis and anti-TG6 concentration was found (p = 0.006 for IgA; p < 0.0001 for IgG). After GFD anti-TG6 concentrations were significantly reduced (p < 0.001). No significant correlation was observed between anti-TG6 and anti-TG2 serum concentrations. Anti-TG6 are more prevalent in children with untreated-CD in absence of overt neurological disorders. The synthesis of the anti-TG6 are related to a longer exposure to gluten before the CD diagnosis and the autoimmunity against TG6 is gluten dependent and disappeared during GFD.

  10. Evolutionary Developments in Interpreting the Gluten-Induced Mucosal Celiac Lesion: An Archimedian Heuristic

    PubMed Central

    Marsh, Michael N.; Heal, Calvin J.

    2017-01-01

    The evolving history of the small intestinal biopsy and its interpretation—and misinterpretations—are described in this paper. Certain interpretative errors in the technical approaches to histological assessment are highlighted—even though we may never be rid of them. For example, mucosal “flattening” does not reduce individual villi to their cores, as still seems to be widely believed. Neither is the mucosa undergoing an atrophic process—since it can recover structurally. Rather, the intestinal mucosa manifests a vast hypertrophic response resulting in the formation of large plateaus formed from partially reduced villi and their amalgamation with the now increased height and width of the inter-villous ridges: this is associated with considerable increases in crypt volumes. Sections through mosaic plateaus gives an erroneous impression of the presence of stunted, flat-topped villi which continues to encourage both the continued use of irrelevant “atrophy” terminologies and a marked failure to perceive what random sections through mosaic plateaus actually look like. While reviewing the extensive 40+ year literature on mucosal analysis, we extracted data on intraepithelial lymphocytes (IEL) counts from 607 biopsies, and applied receiver-operating characteristic (ROC)-curve analysis. From that perspective, it appears that counting IEL/100 enterocyte nuclei in routine haematoxylin and eosin (H&E) sections provides the most useful discriminator of celiac mucosae at histological level, with an effective cut-off of 27 IEL, and offering a very high sensitivity with few false negatives. ROC-curve analysis also revealed the somewhat lesser accuracies of either CD3+ or γδ+ IEL counts. Current official guidelines seem to be somewhat inadequate in clearly defining the spectrum of gluten-induced mucosal pathologies and how they could be optimally interpreted, as well as in promoting the ideal manner for physicians and pathologists to interact in interpreting

  11. Going Gluten-Free: Life with Celiac Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... pasta, and many processed foods. You can eat gluten-free bread, pasta, and other foods that are now easier to find in stores, restaurants, and at special food companies. You also can eat ... if a lip balm contains gluten, you are at risk of consuming it. Some ...

  12. Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation.

    PubMed

    Gibert, Anna; Kruizinga, Astrid G; Neuhold, Susanna; Houben, Geert F; Canela, Miguel A; Fasano, Alessio; Catassi, Carlo

    2013-01-01

    In patients with treated celiac disease (CD), the ingestion of gluten traces contained in gluten-free (GF) wheat substitutes (eg, GF bread, flour, and pasta) could cause persisting intestinal mucosal damage. The objective was to evaluate the proportion of CD patients at risk of mucosal damage due to the consumption of GF products in 4 European countries (Italy, Spain, Germany, and Norway). A probabilistic modeling approach was used to assess the risk of gluten intake at the population level. The input variables were 1) consumption of GF products, 2) concentration of gluten traces in GF products determined by the sandwich R5 ELISA method, and 3) the gluten threshold for mucosal damage of 10 to 50 mg/d. Different population and product availability scenarios were examined for risk assessment. The gluten content of 205 commercially available GF products ranged between <5 and 27.8 mg/kg. Overall, 99.5% of the analyzed samples had a gluten concentration <20 mg/kg. Most (94%) had a gluten concentration below the limit of quantification (5 mg/kg). The mean percentage of the CD European population at risk of mucosal damage resulting from consumption of GF products ranged between 0.01 (Germany) and 0.15 (Italy) and remained very low, even in the worst-case scenario (<1%). The adoption of a single gluten threshold (20 mg/kg) for gluten contamination is suggested. GF products in Europe constitute a very safe option for patients with CD. The dietary follow-up of CD patients should focus on other potential sources of gluten contamination.

  13. From an imbalance to a new imbalance: Italian-style gluten-free diet alters the salivary microbiota and metabolome of African celiac children

    PubMed Central

    Ercolini, Danilo; Francavilla, Ruggiero; Vannini, Lucia; De Filippis, Francesca; Capriati, Teresa; Di Cagno, Raffaella; Iacono, Giuseppe; De Angelis, Maria; Gobbetti, Marco

    2015-01-01

    Fourteen Saharawi celiac children following an African-style gluten-free diet for at least two years were subjected to a change of diet to an Italian-style gluten-free diet for 60 days. Significant differences were identified in the salivary microbiota and metabolome when Saharawi celiac children switched from African- to Italian-style dietary habits. An Italian-style gluten-free diet caused increases in the abundance of Granulicatella, Porphyromonas and Neisseria and decreases in Clostridium, Prevotella and Veillonella, altering the ‘salivary type’ of the individuals. Furthermore, operational taxonomic unit co-occurrence/exclusion patterns indicated that the initial equilibrium of co-occurring microbial species was perturbed by a change in diet: the microbial diversity was reduced, with a few species out-competing the previously established microbiota and becoming dominant. Analysis of predicted metagenomes revealed a remarkable change in the metabolic potential of the microbiota following the diet change, with increased potential for amino acid, vitamin and co-factor metabolism. High concentrations of acetone and 2-butanone during treatment with the Italian-style gluten-free diet suggested metabolic dysfunction in the Saharawi celiac children. The findings of this study support the need for a translational medicine pipeline to examine interactions between food and microbiota when evaluating human development, nutritional needs and the impact and consequences of westernisation. PMID:26681599

  14. Immunological evaluation of the alcohol-soluble protein fraction from gluten-free grains in relation to celiac disease.

    PubMed

    Bergamo, Paolo; Maurano, Francesco; Mazzarella, Giuseppe; Iaquinto, Gaetano; Vocca, Immacolata; Rivelli, Anna Rita; De Falco, Enrica; Gianfrani, Carmen; Rossi, Mauro

    2011-08-01

    Celiac disease (CD) is a gluten-sensitive enteropathy with an immune basis. We established the immune reactivity of the alcohol-soluble fraction from two minor cereals (tef and millet) and two pseudocereals (amaranth and quinoa) which are believed to be nontoxic based on taxonomy. Grains were examined in intestinal T-cell lines (iTCLs), cultures of duodenal explants from HLA-DQ2(+) CD patients and HLA-DQ8 transgenic mice for signs of activation. Our data indicated that tef, millet, amaranth, and quinoa did not show any immune cross-reactivity toward wheat gliadin, and therefore confirming their safety in the diet of CD patients. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources.

    PubMed

    Valerii, Maria Chiara; Ricci, Chiara; Spisni, Enzo; Di Silvestro, Raffaella; De Fazio, Luigia; Cavazza, Elena; Lanzini, Alberto; Campieri, Massimo; Dalpiaz, Alessandro; Pavan, Barbara; Volta, Umberto; Dinelli, Giovanni

    2015-06-01

    Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome whose triggering mechanisms remain unsettled. This study aimed to clarify how cultured peripheral blood mononucleated cells (PBMC) obtained from NCGS patients responded to contact with wheat proteins. Results demonstrated that wheat protein induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS patients, and that the overactivation level depends on the cereal source from which proteins are obtained. CXCL10 is able to decrease the transepithelial resistance of monolayers of normal colonocytes (NCM 460) by diminishing the mRNA expression of cadherin-1 (CDH1) and tight junction protein 2 (TJP2), two primary components of the tight junction strands. Thus, CXCL10 overactivation is one of the mechanisms triggered by wheat proteins in PBMC obtained from NCGS patients. This mechanism is activated to a greater extent by proteins from modern with respect to those extracted from ancient wheat genotypes.

  16. Gluten-sensitive enteropathy coincides with decreased capability of intestinal T cells to secrete IL-17 and IL-22 in a macaque model for celiac disease.

    PubMed

    Xu, Huanbin; Feely, Stephanie L; Wang, Xiaolei; Liu, David X; Borda, Juan T; Dufour, Jason; Li, Weiwei; Aye, Pyone P; Doxiadis, Gaby G; Khosla, Chaitan; Veazey, Ronald S; Sestak, Karol

    2013-04-01

    Celiac disease (CD) is an autoimmune disorder caused by intolerance to dietary gluten. The interleukin (IL)-17 and IL-22 function as innate regulators of mucosal integrity. Impaired but not well-understood kinetics of the IL-17/22 secretion was described in celiac patients. Here, the IL-17 and IL-22-producing intestinal cells were studied upon their in vitro stimulation with mitogens in class II major histocompatibility complex-defined, gluten-sensitive rhesus macaques. Pediatric biopsies were collected from distal duodenum during the stages of disease remission and relapse. Regardless of dietary gluten content, IL-17 and IL-22-producing cells consisted of CD4+ and CD8+ T lymphocytes as well as of lineage-negative (Lin-) cells. Upon introduction of dietary gluten, capability of intestinal T cells to secrete IL-17/22 started to decline (p<0.05), which was paralleled with gradual disruption of epithelial integrity. These data indicate that IL-17/22-producing cells play an important role in maintenance of intestinal mucosa in gluten-sensitive primates.

  17. Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet.

    PubMed

    Nachman, Fabio; Vázquez, Horacio; González, Andrea; Andrenacci, Paola; Compagni, Liliana; Reyes, Hugo; Sugai, Emilia; Moreno, María Laura; Smecuol, Edgardo; Hwang, Hui Jer; Sánchez, Inés Pinto; Mauriño, Eduardo; Bai, Julio César

    2011-03-01

    Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD). We evaluated 133 adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months during the first year and more than 4 years after diagnosis. GERD symptoms were evaluated using a subdimension of the Gastrointestinal Symptoms Rating Scale for heartburn and regurgitation domains. At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (P < .001). At baseline, 30.1% of CD patients had moderate to severe GERD (score >3) compared with 5.7% of controls (P < .01). Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) compared with atypical/silent cases (15.2%; P < .03). A rapid improvement was evidenced at 3 months after initial treatment with a GFD (P < .0001) with reflux scores comparable to healthy controls from this time point onward. GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Pediatric Celiac Disease

    MedlinePlus

    ... Z Celiac Disease Symptoms & Diagnosis Treatment & Management Coping Gluten Free Diet Guide Eosinophilic Esophagitis Inflammatory Bowel Disease ... serious condition caused by a permanent intolerance for gluten--a protein found in wheat, rye, and barley. ...

  19. Essential Amino Acids in the Gluten-Free Diet and Serum in Relation to Depression in Patients with Celiac Disease

    PubMed Central

    van Hees, Nathalie J. M.; Giltay, Erik J.; Tielemans, Susanne M. A. J.; Geleijnse, Johanna M.; Puvill, Thomas; Janssen, Nadine; van der Does, Willem

    2015-01-01

    Introduction Celiac disease (CD) is associated with an increased risk of major depressive disorder, possibly due to deficiencies in micronutrients in the gluten-free diet. We aimed to investigate whether essential amino acids (i.e., the precursors of serotonin, dopamine and other neurotransmitters) are depleted in the diet and serum of CD patients with major depressive disorder. Methods In a cross-sectional study we assessed dietary intake of amino acids and serum levels of amino acids, in 77 CD patients on a gluten-free diet and in 33 healthy controls. Major depressive disorder was assessed with structured interviews (using the Mini International Neuropsychiatric Interview Plus). Dietary intake was assessed using a 203-item food frequency questionnaire. Results Participants had a mean age of 55 years and 74% were women. The intake of vegetable protein was significantly lower in CD patients than in healthy controls (mean difference of 7.8 g/d; 95% CI: 4.7–10.8), as were serum concentrations of tyrosine, phenylalanine and tryptophan (all p < 0.005). However, within the CD patient group, the presence of major depressive disorder (n = 42) was not associated with intake or serum levels of essential amino acids. Conclusions Patients with CD on a long-term gluten-free diet, with good adherence, consume significantly less vegetable protein than controls, and their serum levels of several essential amino acids were also lower. Despite its potential adverse effect, intake and serum levels of essential amino acids were not related to major depression. PMID:25884227

  20. Two prolamin peptides from durum wheat preclude celiac disease-specific T cell activation by gluten proteins.

    PubMed

    De Vincenzi, Massimo; Vincentini, Olimpia; Di Nardo, Giovanni; Boirivant, Monica; Gazza, Laura; Pogna, Norberto

    2010-06-01

    Celiac disease (CD) is a permanent intolerance to wheat prolamins and related proteins displayed by genetically susceptible individuals. Blocking or modulation of CD-specific T cell response by altered prolamin peptides are currently considered as a potential alternative to the only effective therapy of CD based on a life-long gluten-free diet. Two prolamin peptides, the 9-mer ASRVAPGQQ and the 10-mer GTVGVAPGQQ sequences, were identified by mass spectrometry in the peptic/tryptic digest of prolamins (PTP) from durum wheat (Triticum turgidum ssp. durum) cv. Adamello, and investigated for their ability to preclude the stimulation of CD-specific mucosal T cells by gluten proteins. Gluten-specific polyclonal intestinal T cell lines from five CD children (mean age 5 years) were exposed to 50 microg/ml of a deamidated PTP from whole flour of common wheat (T. aestivum) cv. San Pastore, and tested for proliferation and production of interferon-gamma (INF-gamma) and interleukin 10 (IL-10). The same experiment was performed in the presence of 20 microg/ml of the 9-mer or the 10-mer peptide. T cells exposed to PTP showed a threefold increase in proliferation and INF-gamma production, and a significant (P

  1. Pharmacological approaches in celiac disease.

    PubMed

    McCarville, Justin L; Caminero, Alberto; Verdu, Elena F

    2015-12-01

    Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten, characterized by immune responses toward gluten constituents and the autoantigen transglutaminase 2. The only current treatment available for celiac disease is a gluten-free diet, however there are a plethora of therapies in development for the treatment of celiac disease (e.g. vaccine), management of symptoms while consuming gluten (e.g. Necator americanus) or adjuvant therapies in conjunction with the gluten-free diet (e.g. larazotide acetate). Current approaches in development target barrier function, immune responses, detoxifying gluten or sequestering gluten. Developing therapies include those targeting environmental factors, such as the microbiota or proteases.

  2. Gluten-Free Hepatomiracle in “Celiac Hepatitis”: A Case Highlighting the Rare Occurrence of Nutrition-Induced Near Total Reversal of Advanced Steatohepatitis and Cirrhosis

    PubMed Central

    Gaur, Kavita; Sakhuja, Puja; Puri, Amarender S.; Majumdar, Kaushik

    2016-01-01

    Regression of hepatic fibrosis is increasingly becoming a reality, both in clinical as well as experimental models. Reversal or near-total regression of marked liver steatohepatitis and fibrosis, however, remains a rare event. We report the case of a 20-year-old female presenting with diarrhea due to celiac disease and biopsy proven cirrhosis with portal hypertension who had a remarkable clinical improvement in response to a gluten free diet (GFD). A follow-up liver biopsy 9 months after the initiation of GFD revealed a remarkable regression of both fibrosis as well as steatosis. Villous atrophy, as seen in patients with celiac disease, could lead to a deprivation of trophic factors leading to liver injury and subsequent cirrhosis. A gluten-free dietary regimen can produce a reversal of fibrosis leading to the amelioration of symptoms associated even with advanced liver disease. PMID:27976643

  3. A study evaluating the bidirectional relationship between inflammatory bowel disease and self-reported non-celiac gluten sensitivity.

    PubMed

    Aziz, Imran; Branchi, Federica; Pearson, Katherine; Priest, Josephine; Sanders, David S

    2015-04-01

    Non-celiac gluten sensitivity and the associated use of a gluten-free diet (GFD) are perceived to belong to the spectrum of irritable bowel syndrome (IBS). However, recent reports suggest substantial use of a GFD in inflammatory bowel disease (IBD). We assessed the bidirectional relationship between IBD and self-reported non-celiac gluten sensitivity (SR-NCGS). A cross-sectional questionnaire screened for SR-NCGS and the use of a GFD in 4 groups: ulcerative colitis (n = 75), Crohn's disease (n = 70), IBS (n = 59), and dyspeptic controls (n = 109). We also assessed diagnostic outcomes for IBD in 200 patients presenting with SR-NCGS. The prevalence of SR-NCGS was 42.4% (n = 25/59) for IBS, followed by 27.6% (n = 40/145) for IBD, and least among dyspeptic controls at 17.4% (n = 19/109); P = 0.015. The current use of a GFD was 11.9% (n = 7/59) for IBS, 6.2% (n = 9/145) for IBD, and 0.9% (1/109) for dyspeptic controls; P = 0.02. No differences were established between ulcerative colitis and Crohn's disease. However, Crohn's disease patients with SR-NCGS were significantly more likely to have stricturing disease (40.9% versus 18.9%, P = 0.046), and higher mean Crohn's Disease Activity Index score (228.1 versus 133.3, P = 0.002), than those without SR-NCGS. Analysis of 200 cases presenting with SR-NCGS suggested that 98.5% (n = 197) could be dietary-related IBS. However, 1.5% (n = 3) were found to have IBD; such patients had associated alarm symptoms, and/or abnormal blood parameters, prompting colonic investigations. SR-NCGS is not only exclusive to IBS but also associated with IBD, where its presence may be reflecting severe or stricturing disease. Randomized studies are required to further delineate the nature of this relationship and clarify whether a GFD is a valuable dietetic intervention in selected IBD patients.

  4. Celiac Disease-Related Inflammation Is Marked by Reduction of Nkp44/Nkp46-Double Positive Natural Killer Cells

    PubMed Central

    Marafini, Irene; Monteleone, Ivan; Di Fusco, Davide; Sedda, Silvia; Cupi, Maria Laura; Fina, Daniele; Paoluzi, Alessandro Omero; Pallone, Francesco; Monteleone, Giovanni

    2016-01-01

    Introduction and Aim Natural killer (NK) cells are a first line of defence against viruses and down-regulation of NK cell cytotoxic receptors represents one of the strategies by which viruses escape the host’s immune system. Since onset of celiac disease (CD), a gluten-driven enteropathy, has been associated with viral infections, we examined whether CD-associated inflammation is characterized by abnormal distribution of NK cell receptors involved in recognition of viral-infected cells. Materials and Methods Intraepithelial mononuclear cells, isolated from duodenal biopsies of active and inactive CD patients and healthy controls (CTR) and jejunal specimens of obese subjects undergoing gastro-intestinal bypass, were analysed for NK cell markers by flow-cytometry. Expression of granzyme B, interleukin (IL)-22 and tumor necrosis factor (TNF)-α was as assessed in freshly isolated and toll-like receptor (TLR) ligand-stimulated cells. Results The percentages of total NK cells and NKT cells did not significantly differ between CD patients and CTR. In active CD, the fractions of NKp30+ NK cells, NKG2D+ NK cells and NKG2D+ NKT cells were significantly increased as compared to inactive CD patients and CTR. In contrast, CD-associated inflammation was marked by diminished presence of NKG2A+ NK cells and NKG2A+ NKT cells. The fractions of NK cells and NKT cells expressing either NKp44 or NKp46 did not differ between CD and controls, but in CD less NK cells and NKT cells co-expressed these receptors. NKp44/NKp46-double positive cells produced granzyme B and IL-22 but not TNF-α and responded to TLR ligands with enhanced expression of granzyme B. Conclusions These data indicate that active phase of CD associates with reduced presence of NKp44/NKp46-double positive NK cells and NKT cells in the epithelial compartment. PMID:27171408

  5. Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.

    PubMed

    Sellitto, Maria; Bai, Guoyun; Serena, Gloria; Fricke, W Florian; Sturgeon, Craig; Gajer, Pawel; White, James R; Koenig, Sara S K; Sakamoto, Joyce; Boothe, Dustin; Gicquelais, Rachel; Kryszak, Deborah; Puppa, Elaine; Catassi, Carlo; Ravel, Jacques; Fasano, Alessio

    2012-01-01

    Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role

  6. The postprandial glucose response to some varieties of commercially available gluten-free pasta: a comparison between healthy and celiac subjects.

    PubMed

    Bacchetti, T; Saturni, L; Turco, I; Ferretti, G

    2014-11-01

    The objective of the present paper is to evaluate the post-prandial response to some varieties of gluten free (GF) pasta that are commonly consumed in Italy. The glycaemic responses were compared with a glucose standard in healthy subjects and gluten-free diet celiac subjects. Subjects were served portions of the test foods and a standard food (glucose), on separate occasions, each containing 50 g available carbohydrates. Capillary blood glucose was measured from finger-prick samples in fasted subjects and at 15, 30, 45, 60, 90 and 120 minutes after the consumption of each test food. For each type of pasta, the glycaemic index (GI) was calculated by expressing the incremental area under the blood glucose curve as a percentage of each subject's average incremental area under the blood glucose curve (AUC) for the standard food. Gluten free pasta exhibited a range of GI values from 46 to 66. The glycaemic load (GL) and glycaemic profile (GP) were also calculated. A higher GI value was observed in pasta containing rice flour as the main ingredient. Lower values were observed in pasta obtained using corn or a mixture of corn and rice flour as the main ingredients. The results were confirmed in celiac subjects. The information presented in this paper may be useful in helping celiac people to select low-GI pasta.

  7. Celiac sprue.

    PubMed

    Cárdenas, Andrés; Kelly, Ciarán P

    2002-10-01

    Celiac sprue, celiac disease, or gluten-sensitive enteropathy, is a malabsorption disorder of the small intestine that occurs after ingestion of wheat gluten in genetically susceptible individuals. This disease is characterized by intestinal malabsorption associated with villous atrophy of the small intestinal mucosa, clinical and histological improvement after adherence to strict gluten free diet, and relapse when gluten is reintroduced. Celiac sprue has a high prevalence in Western Europe and North America where it is estimated to affect 1:120 to 1:300 individuals. The pathogenesis of celiac sprue is related to inappropriate intestinal T-cell activation in HLA-DQ2 positive individuals triggered by antigenic peptides from wheat gluten or prolamins from barley and rye. Although previously thought to be mainly a disease of childhood onset, the diagnosis is increasingly being made in adults. There are a wide variety of presentations, which range from asymptomatic forms to severe diarrhea, weight loss and nutritional deficiencies. Extraintestinal manifestations including anemia, osteopenia or neurological disorders and associated conditions such as diabetes or hypothyroidism are commonly present. The availability of highly sensitive and specific serologic markers has dramatically facilitated the diagnosis of celiac sprue. However, the demonstration of characteristic histological abnormalities in a biopsy specimen of the small intestine remains the mainstay of diagnosis. Treatment consists of life-long avoidance of dietary gluten to control symptoms and to prevent both immediate and long-term complications.

  8. Transcultural adaptation and validation of the Celiac Dietary Adherence Test. A simple questionnaire to measure adherence to a gluten-free diet.

    PubMed

    Fueyo-Díaz, Ricardo; Gascón-Santos, Santiago; Asensio-Martínez, Ángela; Sánchez-Calavera, María Antonia; Magallón-Botaya, Rosa

    2016-03-01

    A gluten-free diet is to date the only treatment available to celiac disease sufferers. However, systematic reviews indicate that, depending on the method of evaluation used, only 42% to 91% of patients adhere to the diet strictly. Transculturally adapted tools that evaluate adherence beyond simple self-informed questions or invasive analyses are, therefore, of importance. The aim is to obtain a Spanish transcultural adaption and validation of Leffler's Celiac Dietary Adherence Test. A two-stage observational transversal study: translation and back translation by four qualified translators followed by a validation stage in which the questionnaire was administered to 306 celiac disease patients aged between 12 and 72 years and resident in Aragon. Factorial structure, criteria validity and internal consistency were evaluated. The Spanish version maintained the 7 items in a 3-factor structure. Reliability was very high in all the questions answered and the floor and ceiling effects were very low (4.3% and 1%, respectively). The Spearman correlation with the self-efficacy and life quality scales and the self-informed question were statistically significant (p < 0.01). According to the questionnaire criteria, adherence was 72.3%. The Spanish version of the Celiac Dietary Adherence Test shows appropriate psychometric properties and is, therefore, suitable for studying adherence to a gluten-free diet in clinical and research environments.

  9. Improved Quantitation of Gluten in Wheat Starch for Celiac Disease Patients by Gel-Permeation High-Performance Liquid Chromatography with Fluorescence Detection (GP-HPLC-FLD).

    PubMed

    Scherf, Katharina Anne; Wieser, Herbert; Koehler, Peter

    2016-10-12

    Purified wheat starch (WSt) is commonly used in gluten-free products for celiac disease (CD) patients. It is mostly well-tolerated, but doubts about its safety for CD patients persist. One reason may be that most ELISA kits primarily recognize the alcohol-soluble gliadin fraction of gluten, but insufficiently target the alcohol-insoluble glutenin fraction. To address this problem, a new sensitive method based on the sequential extraction of gliadins, glutenins, and gluten from WSt followed by gel-permeation high-performance liquid chromatography with fluorescence detection (GP-HPLC-FLD) was developed. It revealed that considerable amounts of glutenins were present in most WSt. The gluten contents quantitated by GP-HPLC-FLD as sum of gliadins and glutenins were higher than those by R5 ELISA (gluten as gliadin content multiplied by a factor of 2) in 19 out of 26 WSt. Despite its limited selectivity, GP-HPLC-FLD may be applied as confirmatory method to ELISA to quantitate gluten in WSt.

  10. Gluten-specific antibodies of celiac disease gut plasma cells recognize long proteolytic fragments that typically harbor T-cell epitopes

    PubMed Central

    Dørum, Siri; Steinsbø, Øyvind; Bergseng, Elin; Arntzen, Magnus Ø.; de Souza, Gustavo A.; Sollid, Ludvig M.

    2016-01-01

    This study aimed to identify proteolytic fragments of gluten proteins recognized by recombinant IgG1 monoclonal antibodies generated from single IgA plasma cells of celiac disease lesions. Peptides bound by monoclonal antibodies in complex gut-enzyme digests of gluten treated with the deamidating enzyme transglutaminase 2, were identified by mass spectrometry after antibody pull-down with protein G beads. The antibody bound peptides were long deamidated peptide fragments that contained the substrate recognition sequence of transglutaminase 2. Characteristically, the fragments contained epitopes with the sequence QPEQPFP and variants thereof in multiple copies, and they typically also harbored many different gluten T-cell epitopes. In the pull-down setting where antibodies were immobilized on a solid phase, peptide fragments with multivalent display of epitopes were targeted. This scenario resembles the situation of the B-cell receptor on the surface of B cells. Conceivably, B cells of celiac disease patients select gluten epitopes that are repeated multiple times in long peptide fragments generated by gut digestive enzymes. As the fragments also contain many different T-cell epitopes, this will lead to generation of strong antibody responses by effective presentation of several distinct T-cell epitopes and establishment of T-cell help to B cells. PMID:27146306

  11. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

    PubMed

    Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

    2016-02-08

    Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

  12. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

    PubMed Central

    Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

    2016-01-01

    Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

  13. Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease

    PubMed Central

    Tian, Na; Leffler, Daniel A.; Kelly, Ciaran P.; Hansen, Joshua; Marietta, Eric V.; Murray, Joseph A.; Schuppan, Detlef

    2015-01-01

    Celiac disease (CD) is an inflammatory disorder triggered by ingested gluten, causing immune-mediated damage to the small-intestinal mucosa. Gluten proteins are strikingly similar in amino acid composition and sequence to proline-rich proteins (PRPs) in human saliva. On the basis of this feature and their shared destination in the gastrointestinal tract, we hypothesized that salivary PRPs may modulate gluten-mediated immune responses in CD. Parotid salivary secretions were collected from CD patients, refractory CD patients, non-CD patients with functional gastrointestinal complaints, and healthy controls. Structural similarities of PRPs with gluten were probed with anti-gliadin antibodies. Immune responses to PRPs were investigated toward CD patient-derived peripheral blood mononuclear cells and in a humanized transgenic HLA-DQ2/DQ8 mouse model for CD. Anti-gliadin antibodies weakly cross-reacted with the abundant salivary amylase but not with PRPs. Likewise, the R5 antibody, recognizing potential antigenic gluten epitopes, showed negligible reactivity to salivary proteins from all groups. Inflammatory responses in peripheral blood mononuclear cells were provoked by gliadins whereas responses to PRPs were similar to control levels, and PRPs did not compete with gliadins in immune stimulation. In vivo, PRP peptides were well tolerated and nonimmunogenic in the transgenic HLA-DQ2/DQ8 mouse model. Collectively, although structurally similar to dietary gluten, salivary PRPs were nonimmunogenic in CD patients and in a transgenic HLA-DQ2/DQ8 mouse model for CD. It is possible that salivary PRPs play a role in tolerance induction to gluten early in life. Deciphering the structural basis for the lack of immunogenicity of salivary PRPs may further our understanding of the toxicity of gluten. PMID:26505973

  14. Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease.

    PubMed

    Tian, Na; Leffler, Daniel A; Kelly, Ciaran P; Hansen, Joshua; Marietta, Eric V; Murray, Joseph A; Schuppan, Detlef; Helmerhorst, Eva J

    2015-12-01

    Celiac disease (CD) is an inflammatory disorder triggered by ingested gluten, causing immune-mediated damage to the small-intestinal mucosa. Gluten proteins are strikingly similar in amino acid composition and sequence to proline-rich proteins (PRPs) in human saliva. On the basis of this feature and their shared destination in the gastrointestinal tract, we hypothesized that salivary PRPs may modulate gluten-mediated immune responses in CD. Parotid salivary secretions were collected from CD patients, refractory CD patients, non-CD patients with functional gastrointestinal complaints, and healthy controls. Structural similarities of PRPs with gluten were probed with anti-gliadin antibodies. Immune responses to PRPs were investigated toward CD patient-derived peripheral blood mononuclear cells and in a humanized transgenic HLA-DQ2/DQ8 mouse model for CD. Anti-gliadin antibodies weakly cross-reacted with the abundant salivary amylase but not with PRPs. Likewise, the R5 antibody, recognizing potential antigenic gluten epitopes, showed negligible reactivity to salivary proteins from all groups. Inflammatory responses in peripheral blood mononuclear cells were provoked by gliadins whereas responses to PRPs were similar to control levels, and PRPs did not compete with gliadins in immune stimulation. In vivo, PRP peptides were well tolerated and nonimmunogenic in the transgenic HLA-DQ2/DQ8 mouse model. Collectively, although structurally similar to dietary gluten, salivary PRPs were nonimmunogenic in CD patients and in a transgenic HLA-DQ2/DQ8 mouse model for CD. It is possible that salivary PRPs play a role in tolerance induction to gluten early in life. Deciphering the structural basis for the lack of immunogenicity of salivary PRPs may further our understanding of the toxicity of gluten.

  15. The role of gluten consumption at an early age in celiac disease development: a further analysis of the prospective PreventCD cohort study.

    PubMed

    Crespo-Escobar, Paula; Mearin, Maria Luisa; Hervás, David; Auricchio, Renata; Castillejo, Gemma; Gyimesi, Judit; Martinez-Ojinaga, Eva; Werkstetter, Katharina; Vriezinga, Sabine Lisa; Korponay-Szabo, Ilma Rita; Polanco, Isabel; Troncone, Riccardo; Stoopman, Els; Kolaček, Sanja; Shamir, Raanan; Szajewska, Hania; Koletzko, Sibylle; Ribes-Koninckx, Carmen

    2017-04-01

    Background: We previously found that the introduction of small quantities of gluten at 4-6 mo of age did not reduce the risk of celiac disease (CD) in a group of high-risk children. However, the consumption of high amounts of gluten early in life has been suggested to increase CD risk.Objective: The aim of this study was to evaluate this hypothesis by using data from the previous study of the PreventCD trial (www.preventcd.com).Design: Gluten intake was prospectively quantified by using specific food records between 11 and 36 mo of age in 715 children positive for the human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 from 5 European countries. According to the PreventCD protocol, infants received 100 mg immunologically active gluten/d or placebo from 4 to 6 mo of age, with a stepwise and fixed gluten increase until age 10 mo and unrestricted intake thereafter. The primary outcome of the present study was the impact of the amount of gluten consumed from age 10 mo onward on CD development.Results: Mean daily gluten intakes from 10 mo onward were significantly different between countries for children at all ages (P < 0.001) but not between children who developed CD and those who did not within the same country (P > 0.05). The variables country, sex, intervention group, and gluten consumption pattern did not show significant associations with CD development risk (HRs not significant). In addition, the interaction between HLA risk group and gluten consumption pattern showed no significant risk on CD development, except for the DQ2.2/DQ7 haplotype (HR: 5.81; 95% CI: 1.18, 28.74; P = 0.031).Conclusions: Gluten consumption patterns as well as the amount of gluten consumed at 11-36 mo of age do not influence CD development for most related HLA genotypes in children with a genetic risk. This study reports the gluten consumption pattern in children at risk of CD from different European countries. This trial was registered at www.controlled-trials.com as ISRCTN74582487.

  16. Learning to Live Well with Celiac Disease

    MedlinePlus

    ... turn JavaScript on. Feature: Celiac Disease Learning to Live Well with Celiac Disease Past Issues / Spring 2015 ... Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten-Free Spring ...

  17. Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia.

    PubMed

    Daulatzai, Mak Adam

    2015-01-01

    The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are mainly symbiotic and important for well being. However, "dysbiosis" - i.e. an alteration in normal commensal gut microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional "Gut-Brain Axis" pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest, cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence, dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and vulnerability to Alzheimer's disease.

  18. Prevalence of celiac disease and gluten sensitivity in the United States clinical antipsychotic trials of intervention effectiveness study population.

    PubMed

    Cascella, Nicola G; Kryszak, Debra; Bhatti, Bushra; Gregory, Patricia; Kelly, Deanna L; Mc Evoy, Joseph P; Fasano, Alessio; Eaton, William W

    2011-01-01

    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.

  19. Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients

    PubMed Central

    2013-01-01

    Background Patients with persistent symptoms and/or villous atrophy despite strict adherence to a gluten-free diet (GFD) have non-responsive celiac disease (NRCD). A subset of these patients has refractory celiac disease (RCD), yet some NRCD patients may simply be reacting to gluten cross-contamination. Here we describe the effects of a 3-6 month diet of whole, unprocessed foods, termed the Gluten Contamination Elimination Diet (GCED), on NRCD. We aim to demonstrate that this diet reclassifies the majority of patients thought to have RCD type 1 (RCD1). Methods We reviewed the records of all GFD-adherent NRCD patients cared for in our celiac center from 2005-2011 who were documented to have started the GCED. Response to the GCED was defined as being asymptomatic after the diet, with normal villous architecture on repeat biopsy, if performed. Results Prior to the GCED, all patients were interviewed by an experienced dietitian and no sources of hidden gluten ingestion were identified. 17 patients completed the GCED; 15 were female (88%). Median age at start of the GCED was 42 years (range 6-73). Fourteen patients (82%) responded to the GCED. Six patients met criteria for RCD prior to the GCED; 5 (83%) were asymptomatic after the GCED and no longer meet RCD criteria. Of the 14 patients who responded to the GCED, 11 (79%) successfully returned to a traditional GFD without resurgence of symptoms. Conclusions The GCED may be an effective therapeutic option for GFD-adherent NRCD patients. Response to this diet identifies a subgroup of patients, previously classified as RCD1, that is not truly refractory to dietary treatment. Preventing an inaccurate diagnosis of RCD1 avoids immunotherapy. Most patients are able to return to a traditional GFD without return of symptoms. PMID:23448408

  20. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.

    PubMed

    Leffler, Daniel A; Kelly, Ciaran P; Green, Peter H R; Fedorak, Richard N; DiMarino, Anthony; Perrow, Wendy; Rasmussen, Henrik; Wang, Chao; Bercik, Premysl; Bachir, Natalie M; Murray, Joseph A

    2015-06-01

    Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days (P = .017), a 31% increase in improved symptom days (P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment (P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness (P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

    PubMed Central

    Rodrigo, Luis; Pérez-Martinez, Isabel

    2012-01-01

    Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD) with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD), having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD. PMID:22481956

  2. Catch-up growth after the introduction of a gluten-free diet in children with celiac disease.

    PubMed

    Fagundes-Neto, U; Stump, M V; Wehba, J

    1981-01-01

    The rhythm of nutritional recovery in 11 children with celiac disease after the introduction of a gluten-free diet was studied. The mean age of the patients at the moment of the diagnosis was 2.8 +/- 1.2 years and they were followed up for a period of 3.4 +/- 1.9 years. The nutritional status was evaluated by the utilization of the following parameters: the weight-for-age, height-for-age and weight-for-height. It was verified that none child was well nourished at the moment of the diagnosis and during the evolution 9 of them reached a complete recovery of their nutritional status for the weight in a mean period of time of 5.8 +/- 2.7 months; 5 of these children remained well nourished during the follow-up, 3 for 33 months and 1 for just a month. The other 2 children were initially classified as PCM II and turned to PCM I. The height-for-age index revealed that only 6 children had recovered from malnutrition and only 4 remained like this during all the follow-up. The other 2 children suffered nutritional aggravation and turned to be PCM I, but after a mean time of 18.4 months both resumed the rhythm of growth. Nutritional dwarfsism in 45.45% and chronic evoluted malnutrition in 54.55% were the patterns of malnutrition observed in this group of patients.

  3. Rapid Accumulation of CD14+CD11c+ Dendritic Cells in Gut Mucosa of Celiac Disease after in vivo Gluten Challenge

    PubMed Central

    Beitnes, Ann-Christin Røberg; Ráki, Melinda; Brottveit, Margit; Lundin, Knut Erik Aslaksen

    2012-01-01

    Background Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c+ dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c+ or CD103+) and CD163+CD11c− macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge. Methods Treated HLA-DQ2+ CD patients (n = 12) and HLA-DQ2+ gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry. Results In treated CD patients, the gluten challenge increased the density of CD14+CD11c+ DCs, whereas the density of CD103+CD11c+ DCs and CD163+CD11c− macrophages decreased, and the density of CD1c+CD11c+ DCs remained unchanged. Most CD14+CD11c+ DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3+ intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed. Conclusions Rapid accumulation of CD14+CD11c+ DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c+ DCs indicates that these cells are newly recruited monocytes. PMID:22438948

  4. Rapid accumulation of CD14+CD11c+ dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge.

    PubMed

    Beitnes, Ann-Christin Røberg; Ráki, Melinda; Brottveit, Margit; Lundin, Knut Erik Aslaksen; Jahnsen, Frode Lars; Sollid, Ludvig Magne

    2012-01-01

    Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c(+) dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c(+) or CD103(+)) and CD163(+)CD11c(-) macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge. Treated HLA-DQ2(+) CD patients (n = 12) and HLA-DQ2(+) gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry. In treated CD patients, the gluten challenge increased the density of CD14(+)CD11c(+) DCs, whereas the density of CD103(+)CD11c(+) DCs and CD163(+)CD11c(-) macrophages decreased, and the density of CD1c(+)CD11c(+) DCs remained unchanged. Most CD14(+)CD11c(+) DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed. Rapid accumulation of CD14(+)CD11c(+) DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes.

  5. Gluten Sensitivity.

    PubMed

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  6. Anti-gliadin antibodies in breast milk from celiac mothers on a gluten-free diet.

    PubMed

    Roca, María; Vriezinga, Sabine Lisa; Crespo-Escobar, Paula; Auricchio, Renata; Hervás, David; Castillejo, Gemma; Mena, Maria Carmen; Polanco, Isabel; Troncone, Riccardo; Mearin, Maria Luisa; Ribes-Koninckx, Carmen

    2017-05-29

    To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND). 218 samples of mature milk were obtained at different months of lactation (1-6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2 years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit. AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p = 0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p = 0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p < 0.001). AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother's diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers.

  7. Exposure assessment to mycotoxins in gluten-free diet for celiac patients.

    PubMed

    Brera, C; Debegnach, F; De Santis, B; Di Ianni, S; Gregori, E; Neuhold, S; Valitutti, F

    2014-07-01

    Mycotoxins are low molecular weight secondary metabolites produced by certain strains of filamentous fungi such as Aspergillus, Penicillium and Fusarium, which attack crops in the field, and grow on foods also during storage under favorable conditions of temperature and humidity. Foods mainly contributing to the intake of mycotoxins with diet are cereals, maize being the most risky commodity due to the potential co-occurrence of more than one mycotoxin, this can be of particular concern especially for vulnerable group of population such as celiac patients that show increased maize-based products consumption. In this study the exposure of celiac patients to fumonisins (FBs) and zearalenone (ZON) has been assessed. The higher exposures, for all the matrices and for both the selected mycotoxins, were for children age group. The lower and upper bound exposure ranged between 348-582 ng/kg bw/day for FBs and 22-83 ng/kg bw/day for ZON; these values result well below the TDI for the selected mycotoxins, representing the 17-29% and 9-33% of the TDI set for FBs and ZON, respectively. Even considering the worst scenario the exposure values reported for children were lower, namely 1385 ng/kg bw/day for FBs and 237 ng/kg bw/day for ZON, than the corresponding toxicological thresholds.

  8. A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.

    PubMed

    Barone, M; Della Valle, N; Rosania, R; Facciorusso, A; Trotta, A; Cantatore, F P; Falco, S; Pignatiello, S; Viggiani, M T; Amoruso, A; De Filippis, R; Di Leo, A; Francavilla, R

    2016-01-01

    There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

  9. Exposure assessment to fumonisins B1, B2 and B3 through consumption of gluten-free foodstuffs intended for people affected by celiac disease.

    PubMed

    Esposito, Francesco; Fasano, Evelina; Scognamiglio, Gelsomina; Nardone, Antonio; Triassi, Maria; Cirillo, Teresa

    2016-11-01

    Fumonisins are mycotoxins produced by Fusarium species and affecting maize crops. Some analogues of fumonisins are known for their toxic and possible carcinogenic effects on humans and animals. Because of their occurrence in corn-based food, diet is the main source of exposure to these mycotoxins, especially among people affected by celiac disease. Hence, the purpose of this paper was to evaluate the amount of fumonisins B1, B2 and B3 in maize-based products and to assess the exposure of people affected by celiac disease to fumonisins. The sample consisted of 154 gluten-free products analyzed according to method UNI EN 14352:2005. Results showed a heterogeneous contamination by fumoninisin B1, B2 and B3, although below limits of Commission Regulation No 1126/2007 and consistent with other European literature data. Exposure to fumonisins was evaluated for different age groups. In some cases exposure to fumonisins could not be ignored since the total intake could exceed EFSA Provisional Maximum Tolerable Intake up to 150%. Therefore, in the light of an overall contamination by fumonisins the total dietary exposure could be underrated not only in people affected by celiac disease, but also in non-celiac population.

  10. Celiac Disease Changes Everything

    MedlinePlus

    ... has it been to eliminate your intake of gluten? Once you understand how much damage gluten is doing to you, there really isn't ... Learning to Live Well with Celiac Disease / Living Gluten-Free Spring 2015 Issue: Volume 10 Number 1 ...

  11. Downside to Gluten-Free Diets: Diabetes Risk?

    MedlinePlus

    ... Health News on: Celiac Disease Diabetes Type 2 Gluten Sensitivity Recent Health News Related MedlinePlus Health Topics Celiac Disease Diabetes Type 2 Gluten Sensitivity About MedlinePlus Site Map FAQs Customer Support Get ...

  12. Animal models to study gluten sensitivity.

    PubMed

    Marietta, Eric V; Murray, Joseph A

    2012-07-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70-80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease.

  13. Animal Models to Study Gluten Sensitivity1

    PubMed Central

    Marietta, Eric V.; Murray, Joseph A.

    2012-01-01

    The initial development and maintenance of tolerance to dietary antigens is a complex process that, when prevented or interrupted, can lead to human disease. Understanding the mechanisms by which tolerance to specific dietary antigens is attained and maintained is crucial to our understanding of the pathogenesis of diseases related to intolerance of specific dietary antigens. Two diseases that are the result of intolerance to a dietary antigen are celiac disease (CD) and dermatitis herpetiformis (DH). Both of these diseases are dependent upon the ingestion of gluten (the protein fraction of wheat, rye, and barley) and manifest in the gastrointestinal tract and skin, respectively. These gluten-sensitive diseases are two examples of how devastating abnormal immune responses to a ubiquitous food can be. The well-recognized risk genotype for both is conferred by either of the HLA class II molecules DQ2 or DQ8. However, only a minority of individuals who carry these molecules will develop either disease. Also of interest is that the age at diagnosis can range from infancy to 70–80 years of age. This would indicate that intolerance to gluten may potentially be the result of two different phenomena. The first would be that, for various reasons, tolerance to gluten never developed in certain individuals, but that for other individuals, prior tolerance to gluten was lost at some point after childhood. Of recent interest is the concept of non-celiac gluten sensitivity, which manifests as chronic digestive or neurologic symptoms due to gluten, but through mechanisms that remain to be elucidated. This review will address how animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease. PMID:22572887

  14. Molecular and immunological characterization of gluten proteins isolated from oat cultivars that differ in toxicity for celiac disease.

    PubMed

    Real, Ana; Comino, Isabel; de Lorenzo, Laura; Merchán, Francisco; Gil-Humanes, Javier; Giménez, María J; López-Casado, Miguel Ángel; Torres, M Isabel; Cebolla, Ángel; Sousa, Carolina; Barro, Francisco; Pistón, Fernando

    2012-01-01

    A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease (CD). Traditionally, treatment with a GFD has excluded wheat, barley and rye, while the presence of oats is a subject of debate. The most-recent research indicates that some cultivars of oats can be a safe part of a GFD. In order to elucidate the toxicity of the prolamins from oat varieties with low, medium, and high CD toxicity, the avenin genes of these varieties were cloned and sequenced, and their expression quantified throughout the grain development. At the protein level, we have accomplished an exhaustive characterization and quantification of avenins by RP-HPLC and an analysis of immunogenicity of peptides present in prolamins of different oat cultivars. Avenin sequences were classified into three different groups, which have homology with S-rich prolamins of Triticeae. Avenin proteins presented a lower proline content than that of wheat gliadin; this may contribute to the low toxicity shown by oat avenins. The expression of avenin genes throughout the development stages has shown a pattern similar to that of prolamins of wheat and barley. RP-HPLC chromatograms showed protein peaks in the alcohol-soluble and reduced-soluble fractions. Therefore, oat grains had both monomeric and polymeric avenins, termed in this paper gliadin- and glutenin-like avenins. We found a direct correlation between the immunogenicity of the different oat varieties and the presence of the specific peptides with a higher/lower potential immunotoxicity. The specific peptides from the oat variety with the highest toxicity have shown a higher potential immunotoxicity. These results suggest that there is wide range of variation of potential immunotoxicity of oat cultivars that could be due to differences in the degree of immunogenicity in their sequences.

  15. Molecular and Immunological Characterization of Gluten Proteins Isolated from Oat Cultivars That Differ in Toxicity for Celiac Disease

    PubMed Central

    Real, Ana; Comino, Isabel; de Lorenzo, Laura; Merchán, Francisco; Gil-Humanes, Javier; Giménez, María J.; López-Casado, Miguel Ángel; Cebolla, Ángel; Sousa, Carolina; Barro, Francisco; Pistón, Fernando

    2012-01-01

    A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease (CD). Traditionally, treatment with a GFD has excluded wheat, barley and rye, while the presence of oats is a subject of debate. The most-recent research indicates that some cultivars of oats can be a safe part of a GFD. In order to elucidate the toxicity of the prolamins from oat varieties with low, medium, and high CD toxicity, the avenin genes of these varieties were cloned and sequenced, and their expression quantified throughout the grain development. At the protein level, we have accomplished an exhaustive characterization and quantification of avenins by RP-HPLC and an analysis of immunogenicity of peptides present in prolamins of different oat cultivars. Avenin sequences were classified into three different groups, which have homology with S-rich prolamins of Triticeae. Avenin proteins presented a lower proline content than that of wheat gliadin; this may contribute to the low toxicity shown by oat avenins. The expression of avenin genes throughout the development stages has shown a pattern similar to that of prolamins of wheat and barley. RP-HPLC chromatograms showed protein peaks in the alcohol-soluble and reduced-soluble fractions. Therefore, oat grains had both monomeric and polymeric avenins, termed in this paper gliadin- and glutenin-like avenins. We found a direct correlation between the immunogenicity of the different oat varieties and the presence of the specific peptides with a higher/lower potential immunotoxicity. The specific peptides from the oat variety with the highest toxicity have shown a higher potential immunotoxicity. These results suggest that there is wide range of variation of potential immunotoxicity of oat cultivars that could be due to differences in the degree of immunogenicity in their sequences. PMID:23284616

  16. The gluten syndrome: a neurological disease.

    PubMed

    Ford, Rodney Philip Kinvig

    2009-09-01

    Gluten causes symptoms, in both celiac disease and non-celiac gluten-sensitivity, by its adverse actions on the nervous system. Many celiac patients experience neurological symptoms, frequently associated with malfunction of the autonomic nervous system. These neurological symptoms can present in celiac patients who are well nourished. The crucial point, however, is that gluten-sensitivity can also be associated with neurological symptoms in patients who do not have any mucosal gut damage (that is, without celiac disease). Gluten can cause neurological harm through a combination of cross reacting antibodies, immune complex disease and direct toxicity. These nervous system affects include: dysregulation of the autonomic nervous system, cerebella ataxia, hypotonia, developmental delay, learning disorders, depression, migraine, and headache. If gluten is the putative harmful agent, then there is no requirement to invoke gut damage and nutritional deficiency to explain the myriad of the symptoms experienced by sufferers of celiac disease and gluten-sensitivity. This is called "The Gluten Syndrome".

  17. Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease)

    PubMed Central

    Sergi, Consolato; Shen, Fan; Bouma, Gerd

    2017-01-01

    The upper digestive tract is routinely scoped for several causes of malabsorption, and the number of duodenal biopsy specimens has increased notably in the last 10 years. Gluten-sensitive enteropathy (GSE) is an autoimmune disease, which shows an increasing prevalence worldwide and requires a joint clinico-pathological approach. The classical histopathology of GSE with partial or total villous blunting is well recognized, but the classification of GSE is not straightforward. Moreover, several mimickers of GSE with intraepithelial lymphocytosis have been identified in the last 20 years, with drug interactions and medical comorbidities adding to the conundrum. In this review, we report on the normal duodenal mucosa, the clinical presentation and laboratory diagnosis of GSE, the duodenal intraepithelial lymphocytes and immunophenotype of GSE-associated lymphocytes, the GSE mimickers, the differences “across oceans” among guidelines in diagnosing GSE, and the use of a synoptic report for reporting duodenal biopsies in both children and adults in the 21st century. PMID:28216964

  18. Celiac disease.

    PubMed

    Polanco, Isabel

    2008-08-01

    Celiac disease is an immunologically mediated enteropathy of the small intestine, characterized by lifelong intolerance to the gliadin and related prolamines from wheat and other cereals, that occurs in genetically predisposed individuals. Symptoms result from structural damage to the mucosa of the small intestine, which may cause malabsorption with positive autoantibodies in the sera. Normal mucosal architecture is restored after the use of a gluten-free diet and the normalization of the autoantibodies. Villous atrophy and high levels of autoantibodies reappear when gluten is reintroduced into the diet (gluten challenge).

  19. An In Vitro Fermentation Study on the Effects of Gluten Friendly(TM) Bread on Microbiota and Short Chain Fatty Acids of Fecal Samples from Healthy and Celiac Subjects.

    PubMed

    Costabile, Adele; Bergillos-Meca, Triana; Landriscina, Loretta; Bevilacqua, Antonio; Gonzalez-Salvador, Isidro; Corbo, Maria R; Petruzzi, Leonardo; Sinigaglia, Milena; Lamacchia, Carmela

    2017-01-01

    Recently, an innovative gluten detoxification method called Gluten Friendly(TM) (GF) has been developed. It induces structural modifications, which abolish the antigenic capacity of gluten and reduce the in vitro immunogenicity of the most common epitopes involved in celiac disease, without compromising the nutritional and technological properties. This study investigated the in vitro effects of GF bread (GFB) on the fecal microbiota from healthy and celiac individuals by a three-stage continuous fermentative system, which simulates the colon (vessel 1, proximal colon; vessel 2, transverse colon; and vessel 3, distal colon), as well as on the production of short chain fatty acids (SCFA, acetate, propionate, butyrate). The system was fed with GFB and the changes in microbiota through fluorescence in situ hybridization and in SCFA content were assessed. GFB exerted beneficial modulations such as bifidogenic effects in each compartment of the model both with healthy- and celiac-derived samples, as well as growth in Clostridium clusters XIVa+b in celiac-derived samples. Furthermore, increased levels of acetic acid were found in vessel 1 inoculated with the fecal microbiota of healthy individuals, as well as acetic and propionic in vessel 1 and 2 with celiac-derived samples. In addition, the use of multivariate approaches showed that the supplementation of GFB could result in a different modulation of the fecal microbiota and SCFA, as a function of initial equilibrium.

  20. Capsule Endoscopy: A Valuable Tool in the Follow-Up of People With Celiac Disease on a Gluten-Free Diet

    PubMed Central

    Lidums, Ilmars; Teo, Edward; Field, John; Cummins, Adrian G

    2011-01-01

    OBJECTIVES: Traditional celiac disease guidelines recommend follow-up endoscopy and duodenal biopsies at 6–12 months after commencing a gluten-free diet (GFD). However, histology may remain abnormal even 1–2 years later. We evaluated the role of capsule endoscopy in patients with celiac disease after treatment with a GFD. METHODS: Twelve adult patients with newly diagnosed celiac disease were prospectively enrolled. All patients had baseline symptom assessment, celiac serology (tissue transglutaminase antibody, tTG), and capsule endoscopy. Twelve months after commencing a GFD, patients underwent repeat symptom assessment, celiac serology, upper gastrointestinal endoscopy, and capsule endoscopy. RESULTS: At baseline, capsule endoscopy detected endoscopic markers of villous atrophy in the duodenum and extending to a variable distance along the small intestine. On the basis of small bowel transit time, the mean±s.e.m. percentage of small intestine with villous atrophy was 18.2±3.7%. After 12 months on a GFD, repeat capsule endoscopy demonstrated mucosal healing from a distal to proximal direction, and the percentage of small intestine with villous atrophy was significantly reduced to 3.4±1.2% (P=0.0014) and this correlated with improvement in the symptom score (correlation 0.69, P=0.01). There was a significant improvement in symptom score (5.2±1.0 vs. 1.7±0.4, P=0.0012) and reduction in immunoglobulin A–tTG levels (81.5±10.6 vs. 17.5±8.2, P=0.0005). However, 42% of subjects demonstrated persistent villous abnormality as assessed by duodenal histology. CONCLUSIONS: After 12 months on a GFD, patients with celiac disease demonstrate an improvement in symptoms, celiac serology, and the extent of disease as measured by capsule endoscopy. Mucosal healing occurs in a distal to proximal direction. The extent of mucosal healing correlates with improvement in symptoms. Duodenal histology does not reflect the healing that has occurred more distally. PMID:23237971

  1. Genotyping of celiac disease-related-risk haplotypes using a closed-tube polymerase chain reaction analysis of dried blood and saliva disk samples.

    PubMed

    Ollikka, Pia; Raussi, Hanna-Mari; Laitala, Ville; Jaakkola, Lassi; Hovinen, Jari; Hemmilä, Ilkka; Ylikoski, Alice

    2009-03-01

    Expansion of molecular diagnostics more widely into clinical routines requires simplified methods allowing automation. We developed a homogeneous, multilabel polymerase chain reaction (PCR) method based on time-resolved fluorometry, and studied the use of dried disk samples in PCR. Celiac disease-related HLA-DQA1*05, HLA-DQB1*02, and HLA-DQB1*0302 genotyping was used to verify the method with blood and saliva samples dried on S&S 903 and IsoCode sample collection papers. Three sample preparation procedures, including manufacturer's manual elution, an automated elution, and direct use of disk samples, were compared using dried disk samples. The three procedures gave successful amplification and correct genotyping results. Owing to the simplicity of the direct use of disk samples in PCR, this method was chosen for the subsequent homogeneous analysis of blood (n=194) and saliva (n=30) disk samples on S&S 903 paper. The results revealed that, in addition to DNA samples (n=29), both blood and saliva disk samples were successfully amplified and genotyped using the homogeneous PCR assays for HLA-DQA1 and HLA-DQB1. The homogeneous PCR assays developed provide a useful tool to genotype celiac disease-related HLA-DQA1*05, HLA-DQB1*02, and HLA-DQB1*0302 alleles. Furthermore, the method provides a direct way to perform a closed-tube PCR analysis of dried blood and saliva disk samples enabling simple automation.

  2. Tests for Serum Transglutaminase and Endomysial Antibodies Do Not Detect Most Patients With Celiac Disease and Persistent Villous Atrophy on Gluten-free Diets: a Meta-analysis.

    PubMed

    Silvester, Jocelyn A; Kurada, Satya; Szwajcer, Andrea; Kelly, Ciarán P; Leffler, Daniel A; Duerksen, Donald R

    2017-09-01

    Tests to measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) were developed to screen for celiac disease in patients consuming gluten. However, they are commonly used to monitor patients on a gluten-free diet (GFD). We conducted a meta-analysis to assess the sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a GFD. We searched PUBMED, EMBASE, BIOSIS, SCOPUS, clinicaltrials.gov, Science Citation Index, and Cochrane Library databases through November 2016. Inclusion criteria were studies of subjects with biopsy-confirmed celiac disease, follow-up biopsies, and measurement of serum antibodies on a GFD, biopsy performed on subjects regardless of symptoms, or antibody test results. Our analysis excluded subjects with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing GFD. Tests were considered to have positive or negative findings based on manufacturer cut-off values. Villous atrophy was defined as a Marsh 3 lesion or villous height:crypt depth ratio below 3.0. We constructed forest plots to determine the sensitivity and specificity of detection for individual studies. For the meta-analysis, a bivariate random effects model was used to jointly model sensitivity and specificity. Our search identified 5408 unique citations. Following review of abstracts, 442 articles were reviewed in detail. Only 26 studies (6 of tTG assays, 15 of EMA assays, and 5 of tTG and EMA assays) met our inclusion criteria. The most common reason studies were excluded from our analysis was inability to cross-tabulate histologic and serologic findings. The serum assays identified patients with persistent villous atrophy with high levels of specificity: 0.83 for the tTG IgA assay (95% CI, 0.79-0.87) and 0.91 for the EMA IgA assay (95% CI, 0.87-0.94). However, they detected villous atrophy with low levels of sensitivity: 0

  3. Navigating Gluten-Related Health Disorders and Nutritional Considerations of Gluten-Free Diets.

    PubMed

    Gaillard, Leslie A

    2016-01-01

    There are myriad reasons why individuals choose to follow a gluten-free diet, which continues to be a pervasive nutrition trend. This commentary includes a discussion of the most common reasons that patients choose gluten-free foods, including celiac disease and non-celiac gluten sensitivity.

  4. Adherence to a Gluten-Free Diet in Mexican Subjects with Gluten-Related Disorders: A High Prevalence of Inadvertent Gluten Intake.

    PubMed

    Ramírez-Cervantes, Karen Lizzette; Romero-López, Angélica Viridiana; Núñez-Álvarez, Carlos Alberto; Uscanga-Domínguez, Luis F

    2016-01-01

    The rate of compliance with a gluten-free diet in patients with gluten-related disorders is unknown in most Latin American countries. To study the adherence to a gluten-free diet of Mexican individuals with celiac disease and nonceliac gluten sensitivity at the time of their first medical and nutritional consultation at a tertiary referral center. A cross-sectional study was performed. A specific questionnaire was used to gather information on demographics, clinical condition, and self-reported adherence to a gluten-free diet, and to determine strict compliance and intentional or inadvertent gluten consumption. All questionnaires were applied by a nutritionist with expertise in gluten-related disorders. Fifty-six patients with celiac disease and 24 with non-celiac gluten sensitivity were included. Overall, 46 (57.5%) subjects perceived themselves as strictly adherent; however, inadvertent gluten intake was frequent in both celiac disease and non-celiac gluten sensitivity patients (39.2 vs. 33.3%; p = 0.2). Intentional consumption was more prevalent in subjects with celiac disease (48.8 vs. 29.1%; p = 0.048) and individuals with non-celiac gluten sensitivity showed better adherence (37.5 vs. 12.5%; p = 0.035). The importance of a gluten-free diet is underestimated by Mexican patients with celiac disease. The role of a team with expertise in gluten-related disorders is essential to identify inadvertent gluten intake.

  5. The influence of gluten free diet on quantitative ultrasound of proximal phalanxes in children and adolescents with type 1 diabetes mellitus and celiac disease.

    PubMed

    Valerio, Giuliana; Spadaro, Raffaella; Iafusco, Dario; Lombardi, Francesca; Del Puente, Antonio; Esposito, Antonella; De Terlizzi, Francesca; Prisco, Francesco; Troncone, Riccardo; Franzese, Adriana

    2008-08-01

    A reduced bone mineral density has been reported in patients with untreated celiac disease (CD) as well as in patients with poorly controlled type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the bone mineral status by phalangeal quantitative ultrasound in 52 children and adolescents with both diseases (mean age 13.3+/-4.9 years). As a control group 50 patients with T1DM and no CD (age 12.2+/-4.0 years) were studied. The following bone parameters, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were considered and expressed as z score. Compliance to gluten free diet and long term glycemic control (mean of four determinations of HbA1c in the last year) were also assessed. The lowest mean AD-SoS z score values were found in patients with T1DM and CD, who reported transgressions to gluten free diet and exhibited positivity for serum anti-tissue transglutaminase antibodies (tTG) and/or endomysial antibodies (EmA), compared with patients with occasional transgressions but negative for anti-tTG and/or -EmA, patients strictly adherent to the diet, and patients who suffered only from diabetes (ANOVA p=0.021). No difference was found between patients with diabetes alone and patients with both diseases strictly adherent to gluten free diet. Prevalence of osteopenia (z AD-SoS values <-2 SD) was higher in patients with T1DM and CD and poor compliance to the diet (45.5%) compared with patients with T1DM (8%) or patients with both diseases strictly compliant to diet (12.9%) (p=0.015). A negative correlation between Ad-SoS z score and HbA1c (r -0.236, p=0.036) was found when patients with T1DM and patients with T1DM and CD, who strictly adhere to the diet, were pooled. In conclusion the quality of bone as assessed by phalangeal ultrasound in patients with T1DM and CD, who strictly adhere to gluten free diet, is similar to that found in T1DM patients. A higher prevalence of osteopenia is present in patients with both diseases who

  6. HLA-DQ2.5 genes associated with celiac disease risk are preferentially expressed with respect to non-predisposing HLA genes: Implication for anti-gluten T cell response.

    PubMed

    Pisapia, Laura; Camarca, Alessandra; Picascia, Stefania; Bassi, Virginia; Barba, Pasquale; Del Pozzo, Giovanna; Gianfrani, Carmen

    2016-06-01

    HLA genes represent the main risk factor in autoimmune disorders. In celiac disease (CD), the great majority of patients carry the HLA DQA1*05 and DQB1*02 alleles, both of which encode the DQ2.5 molecule. The formation of complexes between DQ2.5 and gluten peptides on antigen-presenting cells (APCs) is necessary to activate pathogenic CD4(+) T lymphocytes. It is widely accepted that the DQ2.5 genes establish the different intensities of anti-gluten immunity, depending whether they are in a homozygous or a heterozygous configuration. Here, we demonstrated that HLA DQA1*05 and DQB1*02 gene expression is much higher than expression of non-CD-associated genes. This influences the protein levels and causes a comparable cell surface exposure of DQ2.5 heterodimers between DQ2.5 homozygous and heterozygous celiac patients. As a consequence, the magnitude of the anti-gluten CD4(+) T cell response is strictly dependent on the antigen dose and not on the DQ2.5 gene configuration of APCs. Furthermore, our findings support the concept that the expression of DQ2.5 genes is an important risk factor in celiac disease. The preferential expression of DQ2.5 alleles provides a new functional explanation of why these genes are so frequently associated with celiac disease and with other autoimmune disorders.

  7. Cardiomyopathy associated with celiac disease.

    PubMed

    Goel, Nisheeth K; McBane, Robert D; Kamath, Patrick S

    2005-05-01

    Celiac disease or celiac sprue is predominantly a disease of the small intestine characterized by chronic malabsorption in genetically susceptible individuals who ingest grains containing gluten, such as wheat, barley, and rye. Although previously believed to be uncommon, celiac disease may be present in up to 1% of the general population. Celiac disease is associated frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, and various connective tissue disorders but is rarely associated with cardiomyopathy. We describe a patient with celiac disease associated with cardiomyopathy whose cardiac function improved substantially after treatment with a gluten-free diet. Cardiomyopathy associated with celiac disease is a serious and potentially lethal condition. However, with early diagnosis and treatment with a gluten-free diet, cardiomyopathy in patients with celiac disease may be completely reversible.

  8. Navigating the gluten-free boom.

    PubMed

    Gaesser, Glenn A; Angadi, Siddhartha S

    2015-08-01

    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.

  9. Dermatitis Herpetiformis: Skin Manifestation of Celiac Disease

    MedlinePlus

    ... a chronic, intensely itchy, blistering skin manifestation of gluten-sensitive enteropathy, commonly known as celiac disease. DH ... external manifestation of an abnormal immune response to gluten, in which IgA antibodies form against the skin ...

  10. Pediatric Celiac Disease

    MedlinePlus

    ... Nurses Print Share Celiac Disease Many kids have sensitivities to certain foods, and the majority are not severe. Celiac disease, however, is a serious condition caused by a permanent intolerance for gluten--a protein found in wheat, rye, and barley. ...

  11. Role of the gluten-free diet on neurological-EEG findings and sleep disordered breathing in children with celiac disease.

    PubMed

    Parisi, P; Pietropaoli, N; Ferretti, A; Nenna, R; Mastrogiorgio, G; Del Pozzo, M; Principessa, L; Bonamico, M; Villa, M P

    2015-02-01

    To determine whether celiac children are at risk for EEG-neurological features and sleep disordered breathing (SDB), and whether an appropriate gluten-free diet (GFD) influences these disorders. We consecutively enrolled 19 children with a new biopsy-proven celiac disease (CD) diagnosis. At CD diagnosis and after 6 months of GFD, each patient underwent a general and neurological examination, an electroencephalogram, a questionnaire about neurological features, and a validated questionnaire about SDB: OSA (obstructive sleep apnea) scores<0 predict normality; values>0 predict OSA. At CD diagnosis, 37% of patients complained headache that affected daily activities and 32% showed positive OSA score. The EEG examinations revealed abnormal finding in 48% of children. After 6 months of GFD headache disappeared in 72% of children and EEG abnormalities in 78%; all children showed negative OSA score. According to our preliminary data, in the presence of unexplained EEG abnormalities and/or other neurological disorders/SDB an atypical or silent CD should also be taken into account. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. Wheat-based foods and non celiac gluten/wheat sensitivity: Is drastic processing the main key issue?

    PubMed

    Fardet, Anthony

    2015-12-01

    While gluten and wheat must be absolutely avoided in coeliac disease and allergy, respectively, nutritional recommendations are largely more confused about non-coeliac wheat/gluten sensitivity (NCWGS). Today, some even recommend avoiding all cereal-based foods. In this paper, the increased NCWGS prevalence is hypothesized to parallel the use of more and more drastic processes applied to the original wheat grain. First, a parallel between gluten-related disorders and wheat processing and consumption evolution is briefly proposed. Notably, increased use of exogenous vital gluten is considered. Drastic processing in wheat technology are mainly grain fractionation and refining followed by recombination and salt, sugars and fats addition, being able to render ultra-processed cereal-based foods more prone to trigger chronic low-grade inflammation. Concerning bread, intensive kneading and the choice of wheat varieties with high baking quality may have rendered gluten less digestible, moving digestion from pancreatic to intestinal proteases. The hypothesis of a gluten resistant fraction reaching colon and interacting with microflora is also considered in relation with increased inflammation. Besides, wheat flour refining removes fiber co-passenger which have potential anti-inflammatory property able to protect digestive epithelium. Finally, some research tracks are proposed, notably the comparison of NCWGS prevalence in populations consuming ultra-versus minimally-processed cereal-based foods.

  13. Confirmation of gluten-free status of wheatgrass

    USDA-ARS?s Scientific Manuscript database

    Celiac Disease (CD) and other gluten related disorders causes both malabsorption of nutrients and an abnormal immune reaction to gluten, the only effective therapy is a gluten-free diet. Codex Alimentarius sets the threshold level at 20 mg/kg gluten for gluten-free foods and this threshold has been ...

  14. Obesity, Metabolic Syndrome, and Cardiovascular Risk in Gluten-Free Followers Without Celiac Disease in the United States: Results from the National Health and Nutrition Examination Survey 2009-2014.

    PubMed

    Kim, Hyun-Seok; Demyen, Michael F; Mathew, Justin; Kothari, Neil; Feurdean, Mirela; Ahlawat, Sushil K

    2017-04-27

    Despite unclear benefits of gluten-free diets (GFD) in the general population, gluten-free followers without medical indications are driving the market. Few studies have investigated health benefits of GFD in the general population. To estimate metabolic and cardiovascular disease (CVD) risk profiles among gluten-free followers without celiac disease (CD). Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. There were 13,523 persons without CD who had GFD information. People with known CVD were excluded. We compared gluten-free followers without CD and the general population by selective metabolic and CVD risk profiles using survey-weighted generalized logistic regression. There were 155 gluten-free followers without CD and CVD, corresponding to a weighted prevalence of 1.3% (3.2 million Americans). Gluten-free followers tended to be women and have a smaller waist circumference and higher HDL cholesterol. They also had a lower BMI with a borderline p value (0.053) and significant self-reported weight loss (-1.33 kg) over one year. Moreover, gluten-free followers were more likely to consider their weight appropriate. There was no statistical difference by age, smoking, hypertension, total cholesterol, triglyceride cholesterol, HbA1c, or fasting glucose. Despite a lower probability of having metabolic syndrome (33.0 vs 38.5%) and lower 10-year CVD risk score (4.52 vs 5.70%) in gluten-free followers, there was no statistical difference. Although being on a GFD may be beneficial in weight management, there was no significant difference in terms of prevalence of metabolic syndrome and CVD risk score in gluten-free followers without CD.

  15. Safety of Adding Oats to a Gluten-Free Diet for Patients With Celiac Disease: Systematic Review and Meta-analysis of Clinical and Observational Studies.

    PubMed

    Pinto-Sánchez, María Inés; Causada-Calo, Natalia; Bercik, Premysl; Ford, Alexander C; Murray, Joseph A; Armstrong, David; Semrad, Carol; Kupfer, Sonia S; Alaedini, Armin; Moayyedi, Paul; Leffler, Daniel A; Verdú, Elena F; Green, Peter

    2017-08-01

    Patients with celiac disease should maintain a gluten-free diet (GFD), excluding wheat, rye, and barley. Oats might increase the nutritional value of a GFD, but their inclusion is controversial. We performed a systematic review and meta-analysis to evaluate the safety of oats as part of a GFD in patients with celiac disease. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases for clinical trials and observational studies of the effects of including oats in GFD of patients with celiac disease. The studies reported patients' symptoms, results from serology tests, and findings from histologic analyses. We used the GRADE approach to assess the quality of evidence. We identified 433 studies; 28 were eligible for analysis. Of these, 6 were randomized and 2 were not randomized controlled trials comprising a total of 661 patients-the remaining studies were observational. All randomized controlled trials used pure/uncontaminated oats. Oat consumption for 12 months did not affect symptoms (standardized mean difference: reduction in symptom scores in patients who did and did not consume oats, -0.22; 95% CI, -0.56 to 0.13; P = .22), histologic scores (relative risk for histologic findings in patients who consumed oats, 0.24; 95% CI, 0.01-4.8; P = .35), intraepithelial lymphocyte counts (standardized mean difference, 0.21; 95% CI, reduction of 1.44 to increase in 1.86), or results from serologic tests. Subgroup analyses of adults vs children did not reveal differences. The overall quality of evidence was low. In a systematic review and meta-analysis, we found no evidence that addition of oats to a GFD affects symptoms, histology, immunity, or serologic features of patients with celiac disease. However, there were few studies for many endpoints, as well as limited geographic distribution and low quality of evidence. Rigorous double-blind, placebo-controlled, randomized controlled trials, using commonly available oats sourced from

  16. [Benefits of gluten-free diet: myth or reality?].

    PubMed

    Coattrenec, Yann; Harr, Thomas; Pichard, Claude; Nendaz, Mathieu

    2015-10-14

    Non celiac gluten sensitivity may explain digestive and general symptoms in patients without celiac disease but this recently described entity is controversial. The role of gluten in comparison to other nutriments such as saccharides and polyols (FODMAPs) remains debated. If a gluten-free diet is clearly indicated in celiac disease and wheat allergy, it remains debatable in non-celiac gluten sensitivity given weak and contradictory evidence. There is no strong evidence for a strict indication to a gluten-free diet in endocrinological, psychiatric, and rheumatologic diseases, or to improve performance in elite sports.

  17. Celiac disease: diagnosis and management.

    PubMed

    Pelkowski, Timothy D; Viera, Anthony J

    2014-01-15

    Celiac disease is an autoimmune disorder of the gastrointestinal tract. It is triggered by exposure to dietary gluten in genetically susceptible individuals. Gluten is a storage protein in wheat, rye, and barley, which are staples in many American diets. Celiac disease is characterized by chronic inflammation of the small intestinal mucosa, which leads to atrophy of the small intestinal villi and subsequent malabsorption. The condition may develop at any age. Intestinal manifestations include diarrhea and weight loss. Common extraintestinal manifestations include iron deficiency anemia, decreased bone mineral density, and neuropathy. Most cases of celiac disease are diagnosed in persons with extraintestinal manifestations. The presence of dermatitis herpetiformis is pathognomonic for celiac disease. Diagnosis is supported by a positive tissue transglutaminase serologic test but, in general, should be confirmed by a small bowel biopsy showing the characteristic histology associated with celiac disease. The presence of human leukocyte antigen alleles DQ2, DQ8, or both is essential for the development of celiac disease, and can be a useful genetic test in select instances. Treatment of celiac disease is a gluten-free diet. Dietary education should focus on identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. About 5% of patients with celiac disease are refractory to a gluten-free diet. These patients should be referred to a gastroenterologist for reconsideration of the diagnosis or for aggressive treatment of refractory celiac disease, which may involve corticosteroids and immunomodulators.

  18. Celiac disease.

    PubMed

    Scherer, John R

    2008-01-01

    Celiac disease is an autoimmune disorder caused by the continued ingestion of gluten, a protein found in wheat, barley and rye, by predisposed individuals. With the development of highly sensitive serologic tests, this has become an increasingly recognized disease with prevalence as high as 1% in certain patient populations, such as Caucasian females. Almost all celiac patients carry the human leukocyte antigen DQ2/DQ8 gene. Much has recently been discovered about the role of the innate immune system in exposing genetically vulnerable patients to the pathogenic gliadin fraction of gluten. The "classical" presentation of chronic diarrhea and malabsorption is now a rarity. Due to earlier detection and increased awareness, celiac disease now presents with a myriad of "atypical" signs and symptoms such as iron-deficiency anemia and osteoporosis. Associated conditions include T-cell lymphoma, dermatitis herpetiformis, autoimmune thyroiditis and type 1 diabetes. Diagnosis requires serologic confirmation with either antiendomysial or antitransglutaminase antibodies as well as histologic confirmation from endoscopic small bowel biopsy. The only effective treatment necessitates a lifelong, continual adherence to a gluten-free diet.

  19. Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet.

    PubMed

    Tapsas, Dimitrios; Fälth-Magnusson, Karin; Högberg, Lotta; Forslund, Tony; Sundqvist, Tommy; Hollén, Elisabet

    2014-11-01

    Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 μM. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, <1400 μM, while 29.8% demonstrated high levels, that is, >1400 μM. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

  20. Acupuncture and a gluten-free diet relieve urticaria and eczema in a case of undiagnosed dermatitis herpetiformis and atypical or extraintestinal celiac disease: a case report

    PubMed Central

    Ohlsen, Bahia A.

    2011-01-01

    Objective The purpose of this case report is to describe the use of acupuncture and a gluten-free diet (GFD) for urticaria and severe eczema in a patient with undiagnosed dermatitis herpetiformis and atypical or extraintestinal celiac disease. Clinical Features A 48-year-old woman presented with intense urticaria, eczema, worsening heartburn, chronic constipation, headaches, and an intense feeling of heat for 4 months. Results of punch biopsies of the skin lesions and laboratory tests were inconclusive. After the acupuncture sessions reported here ended, human leukocyte antigen blood typing revealed celiac disease and dermatitis herpetiformis–associated human leukocyte antigen DQ-8. Results of an endoscopy and colonoscopy were negative. Intervention and Outcome The patient received 3 acupuncture treatments a week for 12 weeks. The patient's symptoms began in March 2008. She began using topical and oral steroids and felt that her symptoms were not responding. Acupuncture began in July 2008. At the end of the first 12 treatments, during which she was using topical and oral steroids, the urticaria and constipation resolved completely; and she had temporary relief from the heartburn. It is thought that the urticaria and constipation resolved because of the acupuncture as that was the only change. At the end of the second 12 treatments, during which time she had started Optifast, a GFD, the heartburn, headache, and eczema resolved. At the end of the third 12 treatments, all her symptoms remained resolved. Steroid treatment was discontinued after the first 12 treatments. Conclusion Acupuncture and diet changes appeared to provide relief from the urticaria and eczema of dermatitis herpetiformis beyond that obtained by traditional treatment of a GFD alone. PMID:22654688

  1. [Gluten migraine].

    PubMed

    Kopishinskaya, S V; Gustov, A V

    2015-01-01

    to study the prevalence of migraine among patients with celiac disease (CD) and clinical features of «gluten migraine» syndrome and to assess the efficacy of gluten diet in its treatment. Authors examined 200 CD patients (main group) and 100 patients with reflux esophagitis and without CD (control group). All patients fulfilled the headache diary during three months before the diagnosis of migraine was made and six months during gluten diet. CD group had migraine syndrome four times more often than the control group (48.5%; p<0.001). In CD group migraine attacks were 2.5 times more frequent than in the control group (р=0.004), but the duration of the attacks was less long, 8 hours in average. The migraine attacks measured by the Visual Analog Scale were less intensive, 55% in average, and had a later onset. The attacks were more frequent in CD patients who were older than 50 years old (р<0.05). The attacks disappeared in 25% of patients with migraine syndrome who were on the gluten diet and the reduction in the intensity and/or frequency of attacks was observed in 38% of patients. We revealed the clear association between migraine syndrome and CD and the high efficacy of gluten diet in the treatment of migraine symptoms.

  2. Swedish children with celiac disease comply well with a gluten-free diet, and most include oats without reporting any adverse effects: a long-term follow-up study.

    PubMed

    Tapsas, Dimitrios; Fälth-Magnusson, Karin; Högberg, Lotta; Hammersjö, Jan-Åke; Hollén, Elisabet

    2014-05-01

    The only known treatment for celiac disease is a gluten-free diet (GFD), which initially meant abstention from wheat, rye, barley, and oats. Recently, oats free from contamination with wheat have been accepted in the GFD. Yet, reports indicate that all celiac disease patients may not tolerate oats. We hypothesized that celiac children comply well with a GFD and that most have included oats in their diet. A food questionnaire was used to check our patients; 316 questionnaires were returned. Mean time on the GFD was 6.9 years, and 96.8% of the children reported that they were trying to keep a strict GFD. However, accidental transgressions occurred in 263 children (83.2%). In 2 of 3 cases, mistakes took place when the patients were not at home. Symptoms after incidental gluten intake were experienced by 162 (61.6%) patients, mostly (87.5%) from the gastrointestinal tract. Small amounts of gluten (<4 g) caused symptoms in 38% of the cases, and 68% reported symptoms during the first 3 hours after gluten consumption. Oats were included in the diet of 89.4% of the children for a mean of 3.4 years. Most (81.9%) ate purified oats, and 45.3% consumed oats less than once a week. Among those who did not consume oats, only 5.9% refrained because of symptoms. General compliance with the GFD was good. Only the duration of the GFD appeared to influence adherence to the diet. Most patients did not report adverse effects after long-term consumption of oats.

  3. Celiac disease: prevention and treatment.

    PubMed

    Selimoğlu, Mukadder Ayşe; Karabiber, Hamza

    2010-01-01

    Celiac disease is a common multisystemic disorder that may be diagnosed at any age. Owing to the increasing prevalence, prevention strategies, including encouragement of breastfeeding and introduction of small amounts of gluten whereas still on breastfeeding at fourth to sixth month of age, become more important than before. For avoiding complications of celiac disease, a strict gluten-free diet is essential. A lifelong gluten-free diet may bring about difficulties as avoiding gluten completely is problematic owing to the contamination with gluten of presumably gluten free foods. New therapeutic approaches include enzyme supplementation, correction of the intestinal barrier defect against gluten entry, blocking of gliadin presentation by human leukocyte antigen blockers and tissue transglutaminase inhibitors.

  4. Normal Bone Mineral Density Associates with Duodenal Mucosa Healing in Adult Patients with Celiac Disease on a Gluten-Free Diet

    PubMed Central

    Larussa, Tiziana; Suraci, Evelina; Imeneo, Maria; Marasco, Raffaella; Luzza, Francesco

    2017-01-01

    Impairment of bone mineral density (BMD) is frequent in celiac disease (CD) patients on a gluten-free diet (GFD). The normalization of intestinal mucosa is still difficult to predict. We aim to investigate the relationship between BMD and duodenal mucosa healing (DMH) in CD patients on a GFD. Sixty-four consecutive CD patients on a GFD were recruited. After a median period of a 6-year GFD (range 2–33 years), patients underwent repeat duodenal biopsy and dual-energy X-ray absorptiometry (DXA) scan. Twenty-four patients (38%) displayed normal and 40 (62%) low BMD, 47 (73%) DMH, and 17 (27%) duodenal mucosa lesions. All patients but one with normal BMD (23 of 24, 96%) showed DMH, while, among those with low BMD, 24 (60%) did and 16 (40%) did not. At multivariate analysis, being older (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.03–1.18) and having diagnosis at an older age (OR 1.09, 95% CI 1.03–1.16) were associated with low BMD; in turn, having normal BMD was the only variable independently associated with DMH (OR 17.5, 95% CI 1.6–192). In older CD patients and with late onset disease, BMD recovery is not guaranteed, despite a GFD. A normal DXA scan identified CD patients with DMH; thus, it is a potential tool in planning endoscopic resampling. PMID:28146115

  5. [New horizons of gluten sensitivity studies].

    PubMed

    Parfenov, A I

    2013-01-01

    Gluten sensitivity may be a cause of gluten-sensitivity celiac disease (GCD). Some gluten-sensitive subjects may have symptoms of GCD, but lack its characteristic changes in the small bowel mucosa (SBM) and a gluten-free diet results in the disappearance of clinical symptoms of GCD. If there is no gluten allergy, the concept "gluten intolerance (GI) unassociated with celiac disease" is applicable in these cases. There is an increase in the prevalence of GCD and GI, which is associated with the use of gluten in food industry to improve the taste and energy density of foods and with the damaging effect of viruses and bacteria on enterocyte membranes, thereby facilitating the penetration of gluten through SBM. The paper gives an update on progress in the diagnosis of GCD and GI and on prospects for designing gluten-free cereals.

  6. Non coeliac gluten sensitivity - A new disease with gluten intolerance.

    PubMed

    Czaja-Bulsa, Grażyna

    2015-04-01

    Until recently gluten intolerance has been believed to be typical of celiac disease (CD) and wheat allergy (WA). In the last few years, however, several study results have been published that have proved that gluten intolerance can also affect people who do not suffer from any of the above mentioned diseases. The new syndrome has been named non-celiac gluten sensitivity (NCGS) or gluten sensitivity (GS). It has been included in the new list of gluten-related disorders published in 2012. Researchers believe that NCGS is the most common syndrome of gluten intolerance. This review discusses many aspects of NCGS epidemiology, pathophysiology, clinical spectrum, and treatment and current tools to identify patients suffering from CD, WA, and NCGS.

  7. [Gluten induced diseases].

    PubMed

    Frič, P; Zavoral, M; Dvořáková, T

    2013-05-01

    The introduction of cereals in human nutrition 10 000 years ago caused the occurrence of gluten induced diseases. This protein complex is involved in pathogenesis of wheat allergy, celiac disease, and gluten sensitivity. Wheat allergy and celiac disease are mediated by the system of adaptive immunity. Gluten sensitivity is a recently defined entity induced by innate immune mechanisms. These subjects present various intestinal and particularly extraintestinal symptoms. The differences between celiac disease and gluten intolerance include permeability of the intestinal mucosal barrier, histology of duodenal biopsy, and mucosal gene expression. The symptoms of gluten sensitivity may also have another genetic background of food intolerance independent of the HLADQ2, - DQ8 system and tissue transglutaminase (eg. in some psychiatric disorders). At present, there is no specific bio-marker of gluten sensitivity. The diagnosis is possible only by exclusion of other causes of symptoms and improvement on a glutenfree diet applied in a doubleblind placebo controlled manner with optional sequence of both stages to exclude the placebo effect due to nutritional intervention.

  8. The obestatin/ghrelin ratio and ghrelin genetics in adult celiac patients before and after a gluten-free diet, in irritable bowel syndrome patients and healthy individuals.

    PubMed

    Russo, Francesco; Chimienti, Guglielmina; Linsalata, Michele; Clemente, Caterina; Orlando, Antonella; Riezzo, Giuseppe

    2017-02-01

    Ghrelin levels and obestatin/ghrelin ratio have been proposed as activity markers in ulcerative colitis, but no data are available in celiac disease (CD) and irritable bowel syndrome (IBS). Our aims were as follows: (a) to assess obestatin and ghrelin concentrations in adult active CD patients, diarrhea-predominant IBS (IBS-d), and healthy controls (HC) in relation to intestinal permeability; (b) to evaluate the ghrelin-obestatin profile in CD patients after a 1-year gluten-free diet (GFD); and (c) to establish the impact of ghrelin genetics. The study included 31 CD patients, 28 IBS-d patients, and 19 HC. Intestinal permeability, assayed by high-performance liquid chromatography determination of urinary lactulose (La)/mannitol (Ma), and circulating concentrations of obestatin, ghrelin, and their ratio were evaluated at enrollment and after GFD. The ghrelin single nucleotide polymorphisms Arg51Gln (rs34911341), Leu72Met (rs696217), and Gln90Leu (rs4684677) were analyzed. Intestinal permeability was impaired in CD patients and ameliorated after GFD. Ghrelin was significantly (P=0.048) higher and the obestatin/ghrelin ratio was significantly (P=0.034) lower in CD patients compared with both IBS-d and HC, and GFD reduced the peptide levels, but without reaching the concentrations in HC. Significant differences (P<0.05) were found in the Leu72Met polymorphism among groups, with the reduction of the GT genotype and the T allele in both CD and IBS-d patients compared with HC. Intestinal permeability is altered in CD, but not in IBS-d patients, and ghrelin levels increase in CD patients as observed in other inflammatory conditions. Moreover, a role for ghrelin genetics is hypothesized in sustaining the many pathogenetic components of these different pathologies, but with a similar symptom profile.

  9. Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease

    PubMed Central

    2013-01-01

    Background Celiac disease (CD) is an autoimmune disorder, characterized by the presence of gastrointestinal and multisystem symptoms, which occasionally mimic those of Irritable Bowel Syndrome (IBS) and Fibromyalgia Syndrome (FMS). To assess the effectiveness of a Gluten-Free Diet (GFD) in seven adult female screening-detected CD subjects, categorized as severe IBS and FMS patients. Methods All subjects showed villous atrophy in duodenal biopsies, were HLA-DQ2/DQ8-positive, and fulfilled the Rome III and ACR 1990 criteria respectively for IBS and FMS classification. GFD effectiveness was assessed at baseline and after 1 year, examining the score changes in the Tender Points (TPs) test, Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), Short Form Health Survey (SF-36), Visual Analogue Scales (VAS) for gastrointestinal complaints, pain and tiredness, drug prescriptions and tissue-Trans-Glutaminase (tTG) serum levels. Results At baseline, all patients had poor Quality of Life and VAS scores, a high number of TPs and drug prescriptions, and increased tTG levels. After 1 year of GFD, all outcome measures significantly improved, with a decrease of 51-60% in TPs, FIQ, HAQ, and VAS scales, and in the number of prescribed drugs, accompanied by an increase of 48-60% in SF-36 Physical and Mental Component Summary scores, and a decrease of tTG to normal values. Conclusion Results of this pilot study show that the adherence to a GFD by CD-related IBS/FMS patients can simultaneously improve CD and IBS/FMS symptoms, and indicate the merit of further research on a larger cohort. PMID:24209578

  10. Gluten contamination in foods labeled as "gluten free" in the United States.

    PubMed

    Lee, Hyun Jung; Anderson, Zach; Ryu, Dojin

    2014-10-01

    Gluten is the main storage protein in grains and consists of gliadin and glutenin occurring in the same ratio. Persons suffering from intolerances, including celiac disease, must avoid foods containing gluten or products containing wheat, barley, and rye. Accordingly, gluten detection is of high interest for the food safety of celiac patients. This study was designed to determine the concentrations of gluten in foods labeled "gluten free" available in the United States. Seventy-eight samples labeled gluten free were collected and analyzed using a gliadin competitive enzyme-linked immunosorbent assay. The gluten content was calculated based on the assumption of the same ratio between gliadin and glutenin. Forty-eight (61.5%) of the 78 samples contained less than the limit of quantification of 10 mg/kg for gluten. In addition, 14 (17.9%) of the 78 samples labeled gluten free contained less gluten than the guidelines established by the Codex Alimentarius for gluten-free labeling (20 mg/kg). However, 16 samples (20.5%) did contain gluten levels of ≥20 mg/kg, ranging from 20.3 to 60.3 mg/kg. In particular, five of eight breakfast cereal samples showed gluten contents higher than 20 mg/kg. These results may be of concern, as gluten sensitivity is known to vary among celiac disease patients.

  11. Nonceliac gluten sensitivity.

    PubMed

    Fasano, Alessio; Sapone, Anna; Zevallos, Victor; Schuppan, Detlef

    2015-05-01

    During the past decade there has been an impressive increase in popularity of the gluten-free diet (GFD)-now the most trendy alimentary habit in the United States and other countries. According to recent surveys, as many as 100 million Americans will consume gluten-free products within a year. Operating under the concept that the GFD benefits only individuals with celiac disease, health care professionals have struggled to separate the wheat from the chaff; there are claims that eliminating gluten from the diet increases health and helps with weight loss, or even that gluten can be harmful to every human being. However, apart from unfounded trends, a disorder related to ingestion of gluten or gluten-containing cereals, namely nonceliac gluten sensitivity (NCGS), has resurfaced in the literature, fueling a debate on the appropriateness of the GFD for people without celiac disease. Although there is clearly a fad component to the popularity of the GFD, there is also undisputable and increasing evidence for NCGS. However, we require a better understanding of the clinical presentation of NCGS, as well as its pathogenesis, epidemiology, management, and role in conditions such as irritable bowel syndrome, chronic fatigue, and autoimmunity. Before we can begin to identify and manage NCGS, there must be agreement on the nomenclature and definition of the disorder based on proper peer-reviewed scientific information. We review the most recent findings on NCGS and outline directions to dissipate some of the confusion related to this disorder.

  12. Celiac disease during pregnancy.

    PubMed Central

    Hancock, Rebecca; Koren, Gideon

    2004-01-01

    QUESTION: One of my patients was diagnosed with celiac disease and maintains a strict gluten-free diet. Is her fetus at risk of neural tube defects because she does not get folic acid from bread and other flour-based foods? ANSWER: A woman with celiac disease must supplement her diet with multivitamins, including folic acid. Most prenatal vitamins contain 0.8 to 0.9 mg of folic acid, double the amount recommended by Health Canada for prevention of neural tube defects. Without supplementation (eg, undiagnosed pregnancy), women with celiac disease might not take in enough folate to maintain protective levels. PMID:15526871

  13. Serum Concentrations of Insulin, Ghrelin, Adiponectin, Leptin, Leptin Receptor and Lipocalin-2 in Children with Celiac Disease Who Do and Do Not Adhere to a Gluten-Free Diet.

    PubMed

    Janas, Roman M; Rybak, Anna; Wierzbicka-Rucińska, Aldona; Socha, Piotr; Śnitko, Rafał; Szaflarska-Popławska, Anna; Stolarczyk, Anna; Oralewska, Beata; Cytra-Jarocka, Elżbieta; Iwańczak, Barbara; Grzybowska-Chlebowczyk, Urszula; Cichy, Wojciech; Czaja-Bulsa, Grażyna; Socha, Jerzy

    2016-07-15

    The roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence). Prepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD). Insulin levels in prepubertal (9.01±4.43 μIU/mL), pubertal (10.3±3.62 μIU/mL), and adolescent (10.8±4.73 μIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 μIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2. Adherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia.

  14. Nonceliac Gluten Sensitivity.

    PubMed

    Vazquez-Roque, Maria; Oxentenko, Amy S

    2015-09-01

    Nonceliac gluten sensitivity (NCGS) is the clinical term used to describe gastrointestinal (GI) and/or extraintestinal symptoms associated with gluten ingestion. The prevalence of NCGS is unknown. The condition has clinical features that overlap with those of celiac disease (CD) and wheat allergy (WA). The pathophysiologic process in NCGS is thought to be through an innate immune mechanism, whereas CD and WA are autoimmune- and allergen-mediated, respectively. However, dietary triggers other than gluten, such as the fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, have been implicated. Currently, no clinical biomarker is available to diagnose NCGS. Exclusion of CD and WA is necessary in the evaluation of a patient suspected to have NCGS. The onset of symptoms in patients with NCGS can occur within hours or days of gluten ingestion. Patients with NCGS have GI and extraintestinal symptoms that typically disappear when gluten-containing grains are eliminated from their diets. However, most patients suspected to have NCGS have already initiated a gluten-free diet at the time of an evaluation. A gluten elimination diet followed by a monitored open challenge of gluten intake to document recurrence of GI and/or extraintestinal symptoms can sometimes be helpful. If NCGS is strongly suggested, then a skilled dietitian with experience in counseling on gluten-free diets can provide proper patient education. Additional research studies are warranted to further our understanding of NCGS, including its pathogenesis and epidemiology, and to identify a biomarker to facilitate diagnosis and patient selection for proper management.

  15. Are xenogeneic anti-tissue transglutaminase antibodies the holy grail for celiac patients?

    PubMed

    Ivanovski, Petar Ilija; Ivanovski, Ivan P; Sedlarevic, Rade

    2007-01-01

    Celiac disease is an immune mediated disorder, the only one with a well-established origin, resulting from a permanent gluten intolerance. Although a gluten-free diet is currently the "safe" and appropriate therapy for celiac disease, this is not always an easy and simple option as "harmful" gluten may contaminate food during the processing and preparation phases. There are also further social pressures, which might be more pressing for young celiac patients, in following a strict gluten-free diet. Therefore, a new therapeutic approaches are sought which would permit celiacs to "peacefully" coexist with gluten. Presently, the most promising looks search for genetically modified wheat lacking toxic gluten peptides and the use of oral endopeptidases in attempt to curb gluten toxicity. Recently discovered role of anti-tissue transglutaminase antibodies in celiac pathogenesis has brought a prospect for a new hypothetical therapeutic approach, an oral immunization of celiacs with xenogeneic anti-tissue transglutaminase antibodies.

  16. Celiac Disease Diagnosis and Management

    PubMed Central

    Leffler, Daniel

    2012-01-01

    Celiac disease is one of the most prevalent autoimmune gastrointestinal disorders but as the case of Ms. J illustrates, diagnosis is often delayed or missed. Based on serology studies, the prevalence of celiac disease in many populations is estimated to be approximately 1% and has been increasing steadily over the last 50 years. Evaluation for celiac disease is generally straightforward, and uses commonly available serologic tests, however the signs and symptoms of celiac disease are nonspecific and highly heterogeneous making diagnosis difficult. While celiac disease is often considered a mild disorder treatable with simple dietary changes, in reality celiac disease imparts considerable risks including reduced bone mineral density, impaired quality of life, and increased overall mortality. In addition, the gluten free diet is highly burdensome and can profoundly affect patients and their families. For these reasons, care of individuals with celiac disease requires prompt diagnosis and ongoing multidisciplinary management. PMID:21990301

  17. Evaluating Sorghum Formulations for a Gluten-Free Beer

    USDA-ARS?s Scientific Manuscript database

    The National Institutes of Health reports that 1% of the United States population suffers from celiac disease, an immune reaction to gluten proteins found in wheat, rye, and barley. There is a limited market of gluten-free products for celiac patients to consume. One product frequently demanded by...

  18. Gluten content of medications.

    PubMed

    Cruz, Joseph E; Cocchio, Craig; Lai, Pak Tsun; Hermes-DeSantis, Evelyn

    2015-01-01

    The establishment of a database for the identification of the presence of gluten in excipients of prescription medications is described. While resources are available to ascertain the gluten content of a given medication, these resources are incomplete and often do not contain a source and date of contact. The drug information service (DIS) at Robert Wood Johnson University Hospital (RWJUH) determined that directly contacting the manufacturer of a product is the best method to determine the gluten content of medications. The DIS sought to establish a resource for use within the institution and create directions for obtaining this information from manufacturers to ensure uniformity of the data collected. To determine the gluten content of a medication, the DIS analyzed the manufacturer's package insert to identify any statement indicating that the product contained gluten or inactive ingredients from known sources of gluten. If there was any question about the source of an inactive ingredient or if no information about gluten content appeared in the package insert, the manufacturer of the particular formulation of the queried medication was contacted to provide clarification. Manufacturers' responses were collected, and medications were categorized as "gluten free," "contains gluten," or "possibly contains gluten." To date, the DIS at RWJUH has received queries about 84 medications and has cataloged their gluten content. The DIS at RWJUH developed a database that categorizes the gluten status of medications, allowing clinicians to easily identify drugs that are safe for patients with celiac disease. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  19. Impaired Bone Microarchitecture Improves After One Year On Gluten-Free Diet: A Prospective Longitudinal HRpQCT Study in Women With Celiac Disease.

    PubMed

    Zanchetta, María Belén; Longobardi, Vanesa; Costa, Florencia; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; de la Paz Temprano, María; Massari, Fabio; Sugai, Emilia; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, José R; Bai, Julio César

    2017-01-01

    We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected

  20. Evolutionary Developments in Interpreting the  Gluten-Induced Mucosal Celiac Lesion: An  Archimedian Heuristic.

    PubMed

    Marsh, Michael N; Heal, Calvin J

    2017-02-28

    The evolving history of the small intestinal biopsy and its interpretation-and misinterpretations-are described in this paper. Certain interpretative errors in the technical approaches to histological assessment are highlighted-even though we may never be rid of them. For example, mucosal "flattening" does not reduce individual villi to their cores, as still seems to be widely believed. Neither is the mucosa undergoing an atrophic process-since it can recover structurally. Rather, the intestinal mucosa manifests a vast hypertrophic response resulting in the formation of large plateaus formed from partially reduced villi and their amalgamation with the now increased height and width of the inter-villous ridges: this is associated with considerable increases in crypt volumes. Sections through mosaic plateaus gives an erroneous impression of the presence of stunted, flat-topped villi which continues to encourage both the continued use of irrelevant "atrophy" terminologies and a marked failure to perceive what random sections through mosaic plateaus actually look like. While reviewing the extensive 40+ year literature on mucosal analysis, we extracted data on intraepithelial lymphocytes (IEL) counts from 607 biopsies, and applied receiver-operating characteristic (ROC)-curve analysis. From that perspective, it appears that counting IEL/100 enterocyte nuclei in routine haematoxylin and eosin (H&E) sections provides the most useful discriminator of celiac mucosae at histological level, with an effective cut-off of 27 IEL, and offering a very high sensitivity with few false negatives. ROC-curve analysis also revealed the somewhat lesser accuracies of either CD3+ or γδ+ IEL counts. Current official guidelines seem to be somewhat inadequate in clearly defining the spectrum of gluten-induced mucosal pathologies and how they could be optimally interpreted, as well as in promoting the ideal manner for physicians and pathologists to interact in interpreting intestinal mucosae

  1. Celiac disease in children.

    PubMed

    Garnier-Lengliné, Hélène; Cerf-Bensussan, Nadine; Ruemmele, Frank M

    2015-10-01

    Celiac disease is an autoimmune enteropathy, triggered by ingestion of gluten in genetically predisposed individuals. Since the use of anti-transglutaminase and anti-endomysium antibodies in the early 1990s, two main groups of clinical presentation can be identified: patients with a symptomatic form of the disease, and patients with a pauci (a)-symptomatic form detected during the work-up of another autoimmune disease or due to a family history of celiac disease. The prevalence of both forms of the disease is currently estimated between 1/100 and 1/400. Classical form of the disease is characterized by occurrence of diarrhoea, failure to thrive, and abdominal bloating in young infants in the months following gluten introduction. Serological tests show high level of anti-transglutaminase and anti-endomysium antibodies. Until recently, the diagnosis required duodenal biopsies that show villous atrophy. HLA genotype can help for diagnosis: the absence of the HLA-DQ2 or DQ8 alleles has a high negative predictive value. European guidelines recently proposed to reconsider the need for systematic endoscopy in typical symptomatic forms with high level of anti-transglutaminase and positive anti-endomysium. These recommendations are being assessed now. Currently, the gluten-free diet remains the only effective treatment for celiac disease. Children with celiac disease have to exclude from their diet all products containing wheat, barley and rye. Gluten-free diet causes clinical remission within a few weeks, but normalization of the small bowel mucosa and negativity of anti-transglutaminase antibodies are obtained in several months or even years. Gluten-free diet is useful to obtain clinical assessment, but also to prevent long-term complications of celiac disease, mainly osteoporosis, other autoimmune diseases, decreased fertility and cancers.

  2. Celiac disease.

    PubMed

    Guandalini, Stefano; Setty, Mala

    2008-11-01

    Research in celiac disease is unraveling new findings at a high rate, and major advances seem to occur in all areas such as genetics, environmental factor, pathophysiology, and even prospective therapeutic implications. New insight is being gained into the interplay between genetic and environmental factors causing celiac disease. In addition to the known human leukocyte antigen haplotypes, genome-wide studies have now identified additional susceptibility loci and the majority of newly discovered risk regions harbor genes controlling immune pathways. The mechanism of translocation of gliadin peptides across the intestinal barrier has been the subject of much investigation, and there is now evidence that the toxic 33-mer peptide can also be translocated transcellularly. As for the paracellular route, this appears to be enhanced by gliadin's stimulation of zonulin release. The growing role of the innate immunity is being recognized and the increased expression of some Toll-like receptors appears to delineate a new inherent defect in this branch of innate immunity. Finally, new perspectives are opening in the treatment of celiac disease based on new detoxified grains, enzymatic degradation of gluten, and prevention of its crossing the mucosal barrier. The pace of new knowledge in this 'ancient' disease is very fast, and this review outlines the principal lines of such exciting developments.

  3. Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.

    PubMed

    Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

    2015-06-05

    Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

  4. Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial

    PubMed Central

    Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

    2015-01-01

    Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients. PMID:26056920

  5. Oral enzyme therapy for celiac sprue

    PubMed Central

    Bethune, Michael T; Khosla, Chaitan

    2012-01-01

    Celiac sprue is an inflammatory disease of the small intestine caused by dietary gluten and treated by adherence to a lifelong gluten-free diet. The recent identification of immunodominant gluten peptides, the discovery of their cogent properties, and the elucidation of the mechanisms by which they engender immunopathology in genetically-susceptible individuals have advanced our understanding of the molecular pathogenesis of this complex disease, enabling the rational design of new therapeutic strategies. The most clinically advanced of these is oral enzyme therapy, in which enzymes capable of proteolyzing gluten (i.e. glutenases) are delivered to the alimentary tract of a celiac sprue patient to detoxify ingested gluten in situ. In this chapter, we discuss the key challenges for discovery and preclinical development of oral enzyme therapies for celiac sprue. Methods for lead identification, assay development, gram-scale production and formulation, and lead optimization for next-generation proteases are described and critically assessed. PMID:22208988

  6. Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy

    PubMed Central

    Verma, Anil K.; Gatti, Simona; Galeazzi, Tiziana; Monachesi, Chiara; Padella, Lucia; Baldo, Giada Del; Annibali, Roberta; Lionetti, Elena; Catassi, Carlo

    2017-01-01

    Background: A strict and lifelong gluten-free diet is the only treatment of celiac disease. Gluten contamination has been frequently reported in nominally gluten-free products. The aim of this study was to test the level of gluten contamination in gluten-free products currently available in the Italian market. Method: A total of 200 commercially available gluten-free products (including both naturally and certified gluten-free products) were randomly collected from different Italian supermarkets. The gluten content was determined by the R5 ELISA Kit approved by EU regulations. Results: Gluten level was lower than 10 part per million (ppm) in 173 products (86.5%), between 10 and 20 ppm in 9 (4.5%), and higher than 20 ppm in 18 (9%), respectively. In contaminated foodstuff (gluten > 20 ppm) the amount of gluten was almost exclusively in the range of a very low gluten content. Contaminated products most commonly belonged to oats-, buckwheat-, and lentils-based items. Certified and higher cost gluten-free products were less commonly contaminated by gluten. Conclusion: Gluten contamination in either naturally or labeled gluten-free products marketed in Italy is nowadays uncommon and usually mild on a quantitative basis. A program of systematic sampling of gluten-free food is needed to promptly disclose at-risk products. PMID:28178205

  7. Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy.

    PubMed

    Verma, Anil K; Gatti, Simona; Galeazzi, Tiziana; Monachesi, Chiara; Padella, Lucia; Baldo, Giada Del; Annibali, Roberta; Lionetti, Elena; Catassi, Carlo

    2017-02-07

    A strict and lifelong gluten-free diet is the only treatment of celiac disease. Gluten contamination has been frequently reported in nominally gluten-free products. The aim of this study was to test the level of gluten contamination in gluten-free products currently available in the Italian market. A total of 200 commercially available gluten-free products (including both naturally and certified gluten-free products) were randomly collected from different Italian supermarkets. The gluten content was determined by the R5 ELISA Kit approved by EU regulations. Gluten level was lower than 10 part per million (ppm) in 173 products (86.5%), between 10 and 20 ppm in 9 (4.5%), and higher than 20 ppm in 18 (9%), respectively. In contaminated foodstuff (gluten > 20 ppm) the amount of gluten was almost exclusively in the range of a very low gluten content. Contaminated products most commonly belonged to oats-, buckwheat-, and lentils-based items. Certified and higher cost gluten-free products were less commonly contaminated by gluten. Gluten contamination in either naturally or labeled gluten-free products marketed in Italy is nowadays uncommon and usually mild on a quantitative basis. A program of systematic sampling of gluten-free food is needed to promptly disclose at-risk products.

  8. Hematologic manifestations of celiac disease

    PubMed Central

    Halfdanarson, Thorvardur R.; Litzow, Mark R.; Murray, Joseph A.

    2007-01-01

    Celiac disease is a common systemic disorder that can have multiple hematologic manifestations. Patients with celiac disease may present to hematologists for evaluation of various hematologic problems prior to receiving a diagnosis of celiac disease. Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication of celiac disease and many patients have anemia at the time of diagnosis. Celiac disease may also be associated with thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency. Patients with celiac disease are at increased risk of being diagnosed with lymphoma, especially of the T-cell type. The risk is highest for enteropathy-type T-cell lymphoma (ETL) and B-cell lymphoma of the gut, but extraintestinal lymphomas can also be seen. ETL is an aggressive disease with poor prognosis, but strict adherence to a gluten-free diet may prevent its occurrence. PMID:16973955

  9. What Is Celiac Disease? How Do I Live with It?

    ERIC Educational Resources Information Center

    Blaska, Joan

    2007-01-01

    Celiac disease, also known as celiac sprue, is a hereditary, autoimmune disease that causes a sensitivity to gluten, which is a protein found in wheat, rye, and barley. The key symptoms of celiac disease are diarrhea, constipation, gas, bloating, backaches, stomachaches, nausea, anemia, fatigue, osteoporosis, stunted growth in children, and weight…

  10. What Is Celiac Disease? How Do I Live with It?

    ERIC Educational Resources Information Center

    Blaska, Joan

    2007-01-01

    Celiac disease, also known as celiac sprue, is a hereditary, autoimmune disease that causes a sensitivity to gluten, which is a protein found in wheat, rye, and barley. The key symptoms of celiac disease are diarrhea, constipation, gas, bloating, backaches, stomachaches, nausea, anemia, fatigue, osteoporosis, stunted growth in children, and weight…

  11. [Oat products in gluten free diet].

    PubMed

    Lange, Ewa

    2007-01-01

    Diagnosis of celiac disease in patent in different age is increased, but gluten free diet is only way to treat this disease. Diet without gluten cereals: wheat, rye, barley and oats is often low in many minerals, vitamins and dietary fiber, but rich in fat and sugar. Gluten free diet witch is supplemented with oats products may contains more dietary fiber, minerals, thiamine, biotin, tokopherols, tokotrienos, and unsaturated fatty acids. The majority of researches show that inclusion 20-50g/d of oat products to gluten free diet is safe for children and adults with new diagnosed and also in remission state. Simultaneously, some patients with celiac disease may intolerance to avenin. The control and assessment of gluten (wheat, rye, barley) contamination in oat products and also long term introduction of oat products to gluten free diet for patient at different age.

  12. Bovine milk intolerance in celiac disease is related to IgA reactivity to alpha- and beta-caseins.

    PubMed

    Cabrera-Chávez, Francisco; de la Barca, Ana María Calderón

    2009-06-01

    Celiac disease is an autoimmune disease triggered mainly by ingestion of wheat gluten proteins. However, some other dietary proteins, such as those of cow's milk, induce celiac disease-like symptoms in some patients with celiac disease. Different approaches have been done to detect the component responsible for this problem, including the possibility of gluten peptides present in cow's milk.

  13. Refractory celiac disease.

    PubMed

    Malamut, Georgia; Cellier, Christophe

    2014-03-01

    A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. Diagnosis of this condition defined as refractory celiac disease (RCD) is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal or abnormal phenotype of intraepithelial lymphocytes. Whereas normal RCD is hardly distinguishable from active CD, abnormal RCD has a severe clinical presentation and a very poor prognosis. We precisely describe below the different types of RCD and propose diagnostic and therapeutic guidelines for its clinical management.

  14. Gluten-related disorders: certainties, questions and doubts.

    PubMed

    Valenti, Simona; Corica, Domenico; Ricciardi, Luisa; Romano, Claudio

    2017-11-01

    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.

  15. Celiac disease: how complicated can it get?

    PubMed

    Tjon, Jennifer May-Ling; van Bergen, Jeroen; Koning, Frits

    2010-10-01

    In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4(+) T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4(+) T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma.

  16. Celiac disease: how complicated can it get?

    PubMed Central

    van Bergen, Jeroen; Koning, Frits

    2010-01-01

    In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4+ T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4+ T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma. PMID:20661732

  17. Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

    PubMed Central

    Balakireva, Anastasia V.; Zamyatnin, Andrey A.

    2016-01-01

    Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders. PMID:27763541

  18. Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities.

    PubMed

    Balakireva, Anastasia V; Zamyatnin, Andrey A

    2016-10-18

    Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders.

  19. [Celiac disease associated with Helicobacter pylori infection].

    PubMed

    Cârdei, E; Moraru, D; Trandafir, Laura; Bozomitu, Laura; Mihăilă, Doina

    2003-01-01

    Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune enteropathy caused by the ingestion of gluten-containing grains in susceptible subjects. The authors present a 3 years and 5 months old girl diagnosed with celiac disease at 1 year and 5 months old. Initially, the evolution after gluten-free diet was favorable. After 2 years the child presented abdominal pain and anorexia. The IgA antigliadin antibodies had normal values. The gastric biopsy found Helicobacter pylori gastritis. After treatment for Helicobacter pylori eradication the symptoms disappeared.

  20. The Gluten-Free Diet: Safety and Nutritional Quality

    PubMed Central

    Saturni, Letizia; Ferretti, Gianna; Bacchetti, Tiziana

    2010-01-01

    The prevalence of Celiac Disease (CD), an autoimmune enteropathy, characterized by chronic inflammation of the intestinal mucosa, atrophy of intestinal villi and several clinical manifestations has increased in recent years. Subjects affected by CD cannot tolerate gluten protein, a mixture of storage proteins contained in several cereals (wheat, rye, barley and derivatives). Gluten free-diet remains the cornerstone treatment for celiac patients. Therefore the absence of gluten in natural and processed foods represents a key aspect of food safety of the gluten-free diet. A promising area is the use of minor or pseudo-cereals such as amaranth, buckwheat, quinoa, sorghum and teff. The paper is focused on the new definition of gluten-free products in food label, the nutritional properties of the gluten-free cereals and their use to prevent nutritional deficiencies of celiac subjects. PMID:22253989

  1. Role of oats in celiac disease.

    PubMed

    Comino, Isabel; Moreno, María de Lourdes; Sousa, Carolina

    2015-11-07

    A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with this condition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of gluten-free ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.

  2. Is celiac disease a lifelong disorder?

    PubMed

    Schmitz, J

    1996-10-01

    That celiac disease is a lifelong disorder was suggested by clinical case records and was considered to have been demonstrated through the widespread use of intestinal biopsies by the end of the 1950s. It was clear that the mucosal lesions observed in children and adults were identical and responded similarly to gluten withdrawal. In fact, in 1970 the European Society for Paediatric Gastroenterology and Nutrition instituted the practice of a challenge after diagnosis. A relapse of clinical symptoms and of the intestinal lesions after gluten was reintroduced into the diet demonstrated the "permanent" nature of sensitivity to gluten in children with celiac disease. Twenty-five years later, the permanence of the sensitivity of the intestinal mucosa to gluten is again a matter of debate. Several lines of evidence, gathered during recent years, show that celiac disease is not always a lifelong condition. First, the long-term follow-up of children with proven celiac disease shows that 10% to 20% of them become "tolerant" (defined on clinical, biological and histologic grounds) to gluten during adolescence. Second, it has also been shown, in individual cases, that the mucosal lesions typical of the disease may appear during adulthood. Our increasing knowledge of the long-term evolution of the disease suggests that celiac disease develops and, in some cases, fades in a predisposed group of people with intestinal sensitivity to gluten, which is probably a common condition. The factors leading to the appearance or disappearance of the disease, however, are still unknown.

  3. Role of oats in celiac disease

    PubMed Central

    Comino, Isabel; Moreno, María de Lourdes; Sousa, Carolina

    2015-01-01

    A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with this condition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of gluten-free ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet. PMID:26557006

  4. Functional replacements for gluten.

    PubMed

    Zannini, Emanuele; Jones, Julie Miller; Renzetti, Stefano; Arendt, Elke K

    2012-01-01

    Celiac disease (CD) is an immune-mediated disease triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. Currently, the only therapy able to normalize the clinical and histological manifestation of the disease is a strict and life-long gluten-free (GF) diet. The replacement of gluten presents a significant technological challenge, as it is an essential structure-building protein, which is necessary for formulating high-quality baked goods. The objective of this paper is to review some basics about CD, its current prevalence, and the recent advances in the preparation of high-quality GF breads using GF flours, starches, hydrocolloids, gums, and novel functional ingredients and technologies.

  5. Interest in medical therapy for celiac disease

    PubMed Central

    Tennyson, Christina A.; Simpson, Suzanne; Lebwohl, Benjamin; Lewis, Suzanne

    2013-01-01

    Objectives: A gluten-free diet is the treatment for celiac disease, but pharmaceutical agents are being developed. The level of interest amongst patients in using a medication to treat celiac disease is unknown. This study examined the level of interest amongst patients in medication to treat celiac disease. Methods: A questionnaire was distributed to celiac disease patients and data were collected on demographics, presentation, and interest in medication. Three validated celiac disease-specific instruments were incorporated: Celiac Disease Associated Quality of Life, the Celiac Symptom Index, and the Celiac Dietary Adherence Test. Results: Responses were received from 365 individuals with biopsy-proven celiac disease. Respondents were 78% (n = 276) female, 48% (n = 170) over 50 years of age, and experienced a classical (diarrhea predominant) presentation in 44% (n = 154). Of the 339 individuals answering the question regarding use of a medication to treat celiac disease, 66% were interested. Interest was greatest in older individuals (71% >50 years of age versus 60% <50 years of age, p = 0.0415), men (78% men versus 62% women, p = 0.0083), frequent restaurant customers (76% versus 58%, p = 0.0006), those dissatisfied with their weight (73% versus 51%, p = 0.0003) and those concerned with the cost of a gluten-free diet (77% versus 64%, p = 0.0176). Length of time since diagnosis, education, presentation, and symptoms with gluten exposure did not demonstrate any effect. Interest in medication was associated with a worse quality of life (CD-QOL 69.4 versus 80.1, p < 0.0001). Conclusions: Most individuals with celiac disease are interested in using a medication. Interest was highest among men, older individuals, frequent restaurant customers, individuals dissatisfied with their weight or concerned with the cost of a gluten-free diet, and those with a worse quality of life. PMID:24003336

  6. Celiac disease: diagnosis, autoimmune mechanisms and treatment.

    PubMed

    Gill, Brian M; Leffler, Daniel A

    2007-09-01

    Celiac disease is a systemic autoimmune disorder triggered by the ingestion of gluten found in wheat and related grains. Once considered rare, celiac disease is now thought to affect more than one in 100 individuals, and is commonly associated with other autoimmune disorders. It predisposes patients to an increased risk of malignancy if left untreated. Celiac disease is HLA restricted as only HLA-DQ2 and -DQ8 are able to bind deamidated gluten with sufficient affinity to trigger an immune response. Both cellular and humoral immune activation occur, leading to local tissue damage and antibody formation. These antibodies, primarily to tissue transglutaminase, are the basis for highly accurate serologic testing, although the gold standard for celiac disease diagnosis remains small intestinal biopsy. Currently, the only treatment for celiac disease is a life-long gluten-free diet, although multiple novel therapeutic modalities are being studied. Although most individuals with celiac disease respond completely to gluten withdrawal, 10-20% have persistent symptoms at some point during their course and less than 1% develop refractory celiac disease, an entity of substantial morbidity.

  7. Nutrition assessment in celiac disease.

    PubMed

    Simpson, Suzanne; Thompson, Tricia

    2012-10-01

    The gluten-free diet is currently the only treatment for celiac disease, and patients should be monitored closely by a dietitian who is knowledgeable regarding this diet. Evaluation by a dietitian includes a comprehensive assessment of dietary history, with an emphasis on caloric and micronutrient intake. Patient knowledge of the gluten-free diet is assessed and interpretation of food labels is taught. Identification of micronutrient deficiencies or comorbid gastrointestinal conditions may occur during a comprehensive dietary assessment. In patients with evidence of gluten exposure, a thorough evaluation for cross-contamination is performed.

  8. Celiac Crisis Associated with Herpes Simplex Virus Esophagitis

    PubMed Central

    Linz, Christopher M.; Tsay, Julie L.; Jin, Ming; El-Dika, Samer S.

    2016-01-01

    Celiac crisis is a rare presentation of celiac disease that is characterized by life-threatening electrolyte abnormalities, vitamin and mineral deficiencies, and diarrhea. Triggers for celiac crisis include major surgeries, pancreatitis, and infections of cytomegalovirus, and salmonella. A 24-year-old woman presented with celiac crisis associated with severe herpes simplex virus (HSV) esophagitis. This case demonstrates that nutritional deficiencies seen in celiac disease can result in a relative immunodeficiency, which may lead to other infectious complications. Additionally, early recognition of celiac crisis is imperative as the metabolic derangements may be life-threatening, and therapy with gluten restriction and nutritional repletion is effective. PMID:27921058

  9. Health-related quality of life in adolescents with screening-detected celiac disease, before and one year after diagnosis and initiation of gluten-free diet, a prospective nested case-referent study.

    PubMed

    Nordyke, Katrina; Norström, Fredrik; Lindholm, Lars; Stenlund, Hans; Rosén, Anna; Ivarsson, Anneli

    2013-02-16

    Celiac disease (CD) is a chronic disorder in genetically predisposed individuals in which a small intestinal immune-mediated enteropathy is precipitated by dietary gluten. It can be difficult to diagnose because signs and symptoms may be absent, subtle, or not recognized as CD related and therefore not prompt testing within routine clinical practice. Thus, most people with CD are undiagnosed and a public health intervention, which involves screening the general population, is an option to find those with unrecognized CD. However, how these screening-detected individuals experience the diagnosis and treatment (gluten-free diet) is not fully understood. The aim of this study is to investigate the health-related quality of life (HRQoL) of adolescents with screening-detected CD before and one year after diagnosis and treatment. A prospective nested case-referent study was done involving Swedish adolescents who had participated in a CD screening study when they were in the sixth grade and about 12 years old. Screening-detected adolescents (n = 103) and referents without CD who participated in the same screening (n = 483) answered questionnaires at the time of the screening and approximately one year after the screening-detected adolescents had received their diagnosis that included the EQ-5D instrument used to measure health status and report HRQoL. The HRQoL for the adolescents with screening-detected CD is similar to the referents, both before and one year after diagnosis and initiation of the gluten-free diet, except in the dimension of pain at follow-up. In the pain dimension at follow-up, fewer cases reported problems than referents (12.6% and 21.9% respectively, Adjusted OR 0.50, 95% CI 0.27-0.94). However, a sex stratified analysis revealed that the significant difference was for boys at follow-up, where fewer screening-detected boys reported problems (4.3%) compared to referent boys (18.8%) (Adjusted OR 0.17, 95% CI 0.04-0.73). The findings of this

  10. Dietary guidelines and implementation for celiac disease.

    PubMed

    Kupper, Cynthia

    2005-04-01

    Medical nutrition therapy is the only accepted treatment for celiac disease. This paper summarizes a review of scientific studies using the gluten-free diet, nutritional risk factors, controversial elements of the diet, and its implementation in treating celiac disease. Treatment for celiac disease requires elimination of the storage proteins found in wheat, rye, and barley. The inclusion of oats and wheat starch is controversial. Research supports that oats may be acceptable for patients with celiac disease and can improve the nutritional quality of the diet. However, use of oats is not widely recommended in the United States because of concerns of potential contamination of commercial oats. Studies assessing the contamination of commercial oats are limited. Research indicates no differences in patients choosing a strict wheat starch-containing, gluten-free diet vs. a naturally gluten-free diet. Factors other than trace gluten may be the cause of continued villous atrophy in some patients. The impact of nutrient malabsorption caused from untreated celiac disease is well documented. The diet and gluten-free products are often low in B vitamins, calcium, vitamin D, iron, zinc, magnesium, and fiber. Few gluten-free products are enriched or fortified, adding to the risk of nutrient deficiencies. Patients newly diagnosed or inadequately treated have low bone mineral density, imbalanced macronutrients, low fiber intake, and micronutrient deficiencies. Also troubling is the increased incidence of obesity seen in persons with celiac disease following a gluten-free diet. Because of the nutritional risks associated with celiac disease, a registered dietitian must be part of the health care team that monitors the patient's nutritional status and compliance on a regular basis.

  11. Management of celiac disease.

    PubMed

    Kalra, K K; Jain, N; Mittal, S K

    1999-01-01

    Celiac disease (CD), perceived as a rare cause of chronic diarrhea three decades ago, was diagnosed as a cause of diarrhea in 60 (7.5%) post weaned children among 800 cases of chronic diarrhea. The diagnosis was established on the basis of a detailed clinical history, histopathological studies on small bowel mucosa and a complete recovery on gluten free diets. Thirty four children were followed up for a period of 0.3 to 8.2 years (mean 3.45 +/- 2.28). Catch up growth was seen in all. A rapid gain in height and weight was observed in first year following exclusion of gluten from the diet. However, on subsequent follow up, flattening of growth curve was seen in 9 subjects which was attributed to non-compliance of gluten free diets and dietary inadequacies. Strict dietary compliance is difficult to adhere to with wheat being a staple cereal in India. Other factors affecting compliance include lack of awareness and non availability of gluten free diets as well as contamination of other items with wheat at grocery shops. A few cases may present as celiac crisis which is a medical emergency requiring aggressive management including use of corticosteroids to improve survival in this otherwise life threatening situation. Effective management of CD requires intense family cooperation as well as concerted national efforts to provide these patients easy access to gluten free diets. The evolution of Celiac Societies, and widespread dissemination of knowledge through all available media will greatly help in management of patients with this chronic disease.

  12. Sourdough lactobacilli and celiac disease.

    PubMed

    Gobbetti, Marco; Giuseppe Rizzello, Carlo; Di Cagno, Raffaella; De Angelis, Maria

    2007-04-01

    Celiac disease (CD) is one of the most common food intolerance. The only effective treatment for CD is a strict adherence to a gluten-free diet throughout the patient's lifetime. Gluten-free products are not widely available and are usually more expensive than their gluten-containing counterparts. There is, therefore, an urgent need to develop safe and effective therapeutic alternatives, to develop high-quality gluten-free products and to investigate the potential of the bread making biotechnology following ancient protocols which include long-time fermentation by selected sourdough lactic acid bacteria. This review describes the most relevant results related to biotechnologies that use selected sourdough lactic acid bacteria and probiotics as starters for sourdough fermentation to investigate their potential to decrease the risk of gluten contamination in gluten-free products. As shown by studies in vitro on celiac intestinal tissue and in vivo on CD patients, the bacterial proteolytic activity is rather promising not only as currently demonstrated for eliminating traces of contaminant gluten but probably also in perspective for the manufacture of tolerated baked goods.

  13. [Neurological disorders associated with gluten sensitivity].

    PubMed

    Hernandez-Lahoz, C; Mauri-Capdevila, G; Vega-Villar, J; Rodrigo, L

    2011-09-01

    Gluten sensitivity is a systemic autoimmune disease that occurs in genetically susceptible individuals on ingesting gluten. It can appear at any age, then becoming a permanent condition. It is more frequent in women, as happens with other autoimmune diseases. Celiac disease is the intestinal form and the most important manifestation among a set of gluten-induced autoimmune pathologies that affect different systems. Neurological manifestations of gluten sensitivity, with or without enteropathy, are also frequent, their pathogenesis including an immunological attack on the central and peripheral nervous tissue accompanied by neurodegenerative changes. The clinical manifestations are varied, but the most common syndromes are cerebellar ataxia and peripheral neuropathy. Finally, gluten sensitivity is associated to a varying degree, with other complex diseases and could influence their evolution. The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.

  14. Clinical and Histologic Mimickers of Celiac Disease.

    PubMed

    Kamboj, Amrit K; Oxentenko, Amy S

    2017-08-17

    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  15. Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease

    PubMed Central

    Gell, Gyöngyvér; Kovács, Krisztina; Veres, Gábor; Korponay-Szabó, Ilma R.; Juhász, Angéla

    2017-01-01

    Brachypodium distachyon, a small annual grass with seed storage globulins as primary protein reserves was used in our study to analyse the toxic nature of non-prolamin seed storage proteins related to celiac disease. The main storage proteins of B. distachyon are the 7S globulin type proteins and the 11S, 12S seed storage globulins similar to oat and rice. Immunoblot analyses using serum samples from celiac disease patients were carried out followed by the identification of immune-responsive proteins using mass spectrometry. Serum samples from celiac patients on a gluten-free diet, from patients with Crohn’s disease and healthy subjects, were used as controls. The identified proteins with intense serum-IgA reactivity belong to the 7S and 11–12S seed globulin family. Structure prediction and epitope predictions analyses confirmed the presence of celiac disease-related linear B cell epitope homologs and the presence of peptide regions with strong HLA-DQ8 and DQ2 binding capabilities. These results highlight that both MHC-II presentation and B cell response may be developed not only to prolamins but also to seed storage globulins. This is the first study of the non-prolamin type seed storage proteins of Brachypodium from the aspect of the celiac disease. PMID:28051174

  16. Celiac disease and overweight in children: an update.

    PubMed

    Diamanti, Antonella; Capriati, Teresa; Basso, Maria Sole; Panetta, Fabio; Di Ciommo Laurora, Vincenzo Maria; Bellucci, Francesca; Cristofori, Fernanda; Francavilla, Ruggiero

    2014-01-02

    The clinical presentation of celiac disease in children is very variable and differs with age. The prevalence of atypical presentations of celiac disease has increased over the past 2 decades. Several studies in adults and children with celiac disease indicate that obesity/overweight at disease onset is not unusual. In addition, there is a trend towards the development of overweight/obesity in celiac patients who strictly comply with a gluten-free diet. However, the pathogenesis and clinical implications of the coexistence of classic malabsorption (e.g., celiac disease) and overweight/obesity remain unclear. This review investigated the causes and main clinical factors associated with overweight/obesity at the diagnosis of celiac disease and clarified whether gluten withdrawal affects the current trends of the nutritional status of celiac disease patients.

  17. Immunomodulatory strategies for celiac disease.

    PubMed

    Rossi, Mauro; Maurano, Francesco; Luongo, Diomira

    2005-01-01

    Celiac disease (CD) is the most common food-sensitive enteropathy in humans and is caused by the lack of immune tolerance (oral tolerance) to gluten. The identification of gluten-specific T cells in the lamina propria of celiacs and the strong association with HLA-DQ2 and -DQ8 genes support a central role of CD4(+) T cells in CD pathogenesis. Studies focused on the modulation of autoimmunity in different experimental models highlighted possible immune therapeutic protocols useful also for the management of CD. On the basis of these observations, a series of strategies have been designed: some of them are based on the identification of immunogenic epitopes and their suppression via enzymatic treatment or by using peptide analogues; others rely on the delivery of unmodified antigen through the nasal route or coadministered with downregulatory cytokines. studies are generally early stage but encouraging in paving a way for an alternative treatment for celiac disease.

  18. Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome.

    PubMed

    Barmeyer, Christian; Schumann, Michael; Meyer, Tim; Zielinski, Christina; Zuberbier, Torsten; Siegmund, Britta; Schulzke, Jörg-Dieter; Daum, Severin; Ullrich, Reiner

    2017-01-01

    Irritable bowel syndrome (IBS) is common but therapies are unsatisfactory. Food is often suspected as cause by patients, but diagnostic procedures, apart from allergy testing, are limited. Based on the hypothesis of non-celiac wheat sensitivity (WS) in a subgroup of IBS patients, we tested the long-term response to a gluten-free diet (GFD) and investigated HLA-DQ2 or -DQ8 expression as a diagnostic marker for WS in diarrhea-dominant (IBS-D) and mixed-type IBS (IBS-M). The response to a GFD served as reference test for WS and HLA-DQ2/8 expression was determined as index test. Patients were classified as responders if they reported complete or considerable relief of IBS symptoms on at least 75 % of weeks over a 4-month period of gluten-free diet. Established questionnaires (IBS-Quality of Life (IBS-QoL), IBS Symptom Severity Scale (IBS-SSS), European Quality of Life-5 Dimensions (EQ-5D)) were used for secondary outcome measures. Thirty-five patients finished the study. Of these, 12 (34 %) were responders and classified as having WS (95 % CI 21-51 %). HLA-DQ2/8 expression had a specificity of 52 % (95 % CI 33-71 %) and sensitivity of 25 % (95 % CI 8-54 %) for WS. Responders showed improvement in quality of life and symptom scores. At 1-year follow-up, all responders and 55 % of non-responders were still on GFD and reported symptom relief. Using strict criteria as recommended for IBS studies, about one third of patients with IBS-D or IBS-M are wheat sensitive, with a similar proportion in both IBS types. Expression of HLA-DQ2/8 is not useful as diagnostic marker for WS. Long-term adherence to a GFD is high and can sustain symptomatic improvement.

  19. Microbiome and Gluten.

    PubMed

    Sanz, Yolanda

    2015-01-01

    Celiac disease (CD) is a frequent chronic inflammatory enteropathy caused by gluten in genetically predisposed individuals that carry disease susceptibility genes (HLA-DQ2/8). These genes are present in about 30-40% of the general population, but only a small percentage of carriers develops CD. Gluten is the key environmental trigger of CD, but its intake does not fully explain disease onset; indeed, an increased number of cases experience gluten intolerance in late adulthood after many years of gluten exposure. Consequently, additional environmental factors seem to be involved in CD. Epidemiological studies indicate that common perinatal and early postnatal factors influence both CD risk and intestinal microbiota structure. Prospective studies in healthy infants at risk of developing CD also reveal that the HLA-DQ genotype, in conjunction with other environmental factors, influences the microbiota composition. Furthermore, CD patients have imbalances in the intestinal microbiota (dysbiosis), which are not fully normalized despite their adherence to a gluten-free diet. Therefore, it is hypothesized that the disease can promote dysbiosis that aggravates CD pathogenesis, and dysbiosis, in turn, can initiate and sustain inflammation through the expansion of proinflammatory pathobionts and decline of anti-inflammatory mutualistic bacteria. Studies in experimental models are also contributing to understand the role of intestinal bacteria and its interactions with a predisposed genotype in promoting CD. Advances in this area could aid in the development of microbiome-informed intervention strategies that optimize the partnership between the gut microbiota and host immunity for improving CD management.

  20. Serological tests in gluten sensitivity (nonceliac gluten intolerance).

    PubMed

    Volta, Umberto; Tovoli, Francesco; Cicola, Ronny; Parisi, Claudia; Fabbri, Angela; Piscaglia, Maria; Fiorini, Erica; Caio, Giacomo

    2012-09-01

    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.

  1. The widening spectrum of celiac disease.

    PubMed

    Murray, J A

    1999-03-01

    Celiac disease is a permanent intolerance to ingested gluten that results in immunologically mediated inflammatory damage to the small-intestinal mucosa. Celiac disease is associated with both human leukocyte antigen (HLA) and non-HLA genes and with other immune disorders, notably juvenile diabetes and thyroid disease. The classic sprue syndrome of steatorrhea and malnutrition coupled with multiple deficiency states may be less common than more subtle and often monosymptomatic presentations of the disease. Diverse problems such as dental anomalies, short stature, osteopenic bone disease, lactose intolerance, infertility, and nonspecific abdominal pain among many others may be the only manifestations of celiac disease. The rate at which celiac disease is diagnosed depends on the level of suspicion for the disease. Although diagnosis relies on intestinal biopsy findings, serologic tests are useful as screening tools and as an adjunct to diagnosis. The treatment of celiac disease is lifelong avoidance of dietary gluten. Gluten-free diets are now readily achievable with appropriate professional instruction and community support. Both benign and malignant complications of celiac disease occur but these can often be avoided by early diagnosis and compliance with a gluten-free diet.

  2. Celiac disease

    PubMed Central

    Rodrigo, Luis

    2006-01-01

    Celiac disease (CD) is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-II antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 (tTG), appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the “gold standard” for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.

  3. Estimated levels of gluten incidentally present in a Canadian gluten-free diet.

    PubMed

    La Vieille, Sébastien; Dubois, Sheila; Hayward, Stephen; Koerner, Terence B

    2014-02-21

    Avoiding exposure to gluten is currently the only effective treatment for celiac disease. However, the evidence suggests that for most affected individuals, exposure to less than 10 mg/day is unlikely to cause histological changes to the intestinal mucosa. The daily diet of people with celiac disease does not rely solely on gluten-free pre-packaged foods, but also on naturally gluten-free grains (e.g., rice, buckwheat, ...) and foods with grain-derived ingredients (i.e., flour and starches) used for cooking and baking at home. The objective of this study was to estimate the level of incidental gluten potentially present in gluten-free diets from a Canadian perspective. We have conducted gluten exposure estimations from grain-containing foods and foods with grain-derived ingredients, taking into consideration the various rates of food consumption by different sex and age groups. These estimates have concluded that if gluten was present at levels not exceeding 20 ppm, exposure to gluten would remain below 10 mg per day for all age groups studied. However, in reality the level of gluten found in naturally gluten-free ingredients is not static and there may be some concerns related to the flours made from naturally gluten-free cereal grains. It was found that those containing a higher level of fiber and that are frequently used to prepare daily foods by individuals with celiac disease could be a concern. For this category of products, only the flours and starches labelled "gluten-free" should be used for home-made preparations.

  4. Estimated Levels of Gluten Incidentally Present in a Canadian Gluten-Free Diet

    PubMed Central

    Vieille, Sébastien La; Dubois, Sheila; Hayward, Stephen; Koerner, Terence B.

    2014-01-01

    Avoiding exposure to gluten is currently the only effective treatment for celiac disease. However, the evidence suggests that for most affected individuals, exposure to less than 10 mg/day is unlikely to cause histological changes to the intestinal mucosa. The daily diet of people with celiac disease does not rely solely on gluten-free pre-packaged foods, but also on naturally gluten-free grains (e.g., rice, buckwheat, ...) and foods with grain-derived ingredients (i.e., flour and starches) used for cooking and baking at home. The objective of this study was to estimate the level of incidental gluten potentially present in gluten-free diets from a Canadian perspective. We have conducted gluten exposure estimations from grain-containing foods and foods with grain-derived ingredients, taking into consideration the various rates of food consumption by different sex and age groups. These estimates have concluded that if gluten was present at levels not exceeding 20 ppm, exposure to gluten would remain below 10 mg per day for all age groups studied. However, in reality the level of gluten found in naturally gluten-free ingredients is not static and there may be some concerns related to the flours made from naturally gluten-free cereal grains. It was found that those containing a higher level of fiber and that are frequently used to prepare daily foods by individuals with celiac disease could be a concern. For this category of products, only the flours and starches labelled “gluten-free” should be used for home-made preparations. PMID:24566442

  5. Immunological characterization of the gluten fractions and their hydrolysates from wheat, rye and barley.

    PubMed

    Rallabhandi, Prasad; Sharma, Girdhari M; Pereira, Marion; Williams, Kristina M

    2015-02-18

    Gluten proteins in wheat, rye and barley cause celiac disease, an autoimmune disorder of the small intestine, which affects approximately 1% of the world population. Gluten is comprised of prolamin and glutelin. Since avoidance of dietary gluten is the only option for celiac patients, a sensitive gluten detection and quantitation method is warranted. Most regulatory agencies have set a threshold of 20 ppm gluten in foods labeled gluten-free, based on the currently available ELISA methods. However, these methods may exhibit differences in gluten quantitation from different gluten-containing grains. In this study, prolamin and glutelin fractions were isolated from wheat, rye, barley, oats and corn. Intact and pepsin-trypsin (PT)-digested prolamin and glutelin fractions were used to assess their immunoreactivity and gluten recovery by three sandwich and two competitive ELISA kits. The Western blots revealed varied affinity of ELISA antibodies to gluten-containing grain proteins and no reactivity to oat and corn proteins. ELISA results showed considerable variation in gluten recoveries from both intact and PT-digested gluten fractions among different kits. Prolamin fractions showed higher gluten recovery compared to their respective glutelin fractions. Among prolamins, barley exhibited higher recovery compared to wheat and rye with most of the ELISA kits used. Hydrolysis resulted in reduced gluten recovery of most gluten fractions. These results suggest that the suitability of ELISA for accurate gluten quantitation is dependent upon various factors, such as grain source, antibody specificity, gluten proteins and the level of their hydrolysis in foods.

  6. [Treatment and management of celiac disease].

    PubMed

    Holtmeier, W

    2006-11-01

    In most patients the clinical course of celiac disease is unproblematic after the diagnosis has been made and a strict gluten-free diet is established. However, in rare cases complications like refractory sprue or lymphoma can occur. Individual management is required since the clinical presentation of celiac disease can be very heterogeneous. For example, it is a matter of controversy if asymptomatic patients, who have the same typical histological changes in their small bowel like patients with symptomatic celiac disease, should adhere to a gluten-free diet. A major problem is the compliance and the unintentional intake of gluten. A 100 % gluten-free diet is not possible since most food components are contaminated with trace amounts of gluten. Fortunately most patients tolerate these contaminations. Furthermore, the threshold for gluten contamination can differ highly among patients. One central point in patient care is the monitoring of a gluten-free diet and the timely recognition of complications. Therefore, the role of antibodies and duodenal histology in monitoring the course of the disease will be discussed.

  7. Neuropsychiatric symptoms and celiac disease

    PubMed Central

    Urban-Kowalczyk, Małgorzata; Œmigielski, Janusz; Gmitrowicz, Agnieszka

    2014-01-01

    Background Neuropsychiatric symptoms may represent an atypical manifestation of celiac disease that occur before a gastroenterological diagnosis is made. Some studies suggest that a gluten-free diet is effective in treating the depression, anxiety, and neurological complications associated with celiac disease. Method The article describes the case of a patient suffering from chronic, treatment-resistant symptoms of depression and anxiety. The diagnosis of celiac disease and introduction of an elimination diet caused a significant improvement in mental state and everyday functioning in the presenting patient. Conclusion The presence of persistent anxiety and depressive symptoms, with a poor reaction to pharmacological treatment, indicates a need to identify somatic reasons for the underlying condition. It is important to remember that celiac disease can occur at any age, not only in childhood. The presence of this somatic cause of persistent depressive and anxiety symptoms should be considered in the diagnostic process in adults. PMID:25342904

  8. Gluten-free food as source of hidden allergen (lupine).

    PubMed

    Rossi, G; Amato, S; Mistrello, G

    2009-08-01

    A woman, 68 yrs, developed an anaphylactic reaction after tasting a few pieces of gluten-free pasta. She was not celiac but was preparing a meal for her celiac nephew. The culprit pasta contained lupine flour and lupine proteins. Prick test with lupine extract was positive. ELISA and immunoblot analysis showed the presence of specific IgE to lupine in patient's serum.

  9. Improved viscoelastic zein-starch doughs for leavened gluten-free breads: Their rheology and microstructure

    USDA-ARS?s Scientific Manuscript database

    Celiac disease is an autoimmune enteropathy triggered by protein sequences in wheat, rye and barley. Permitted gluten-free grains include rice, maize and sorghum. Traditional gluten-free breads are made from soft, batter-like doughs based on these gluten-free grains, and are often of very poor quali...

  10. Nutritional differences between a gluten-free diet and a diet containing equivalent products with gluten.

    PubMed

    Miranda, J; Lasa, A; Bustamante, M A; Churruca, I; Simon, E

    2014-06-01

    The gluten-free (GF) products market represents one of the most prosperous markets in the field of food and beverages in the immediate future. Historically, counselling for celiac disease has focused on the absence of gluten in foods, however the nutritional quality of GF foodstuffs is an important aspect to consider. The aim of the present work was to compare the nutritional composition of the 206 GF rendered products most consumed in Spain, against the composition of 289 equivalent foods with gluten, and to make a comparison between the diet including GF products and the same diet with equivalent products with gluten in a 58 adult celiac population. The results of the present collaborative study pointed out differences in calorie, macronutrient, fiber, sodium, salt and cholesterol content between GF rendered and gluten-containing foodstuffs. Thus, calorie and nutrient intake in a GF diet is different when compared to its equivalent diet with gluten. Following a diet based on GF products could suppose a nutritional imbalance for celiac patients as well as for non-celiacs who follow a diet that includes many GF rendered foodstuffs.

  11. New aspects in celiac disease

    PubMed Central

    Torres, MI; López Casado, MA; Ríos, A

    2007-01-01

    Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA-DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. CD is caused by the lack of immune tolerance (oral tolerance) to wheat gluten. In this sense, the expression of soluble HLA-G in CD is of special interest because the molecule plays an important role in the induction of immune tolerance. The enhanced expression of soluble HLA-G found in CD may be part of a mechanism to restore the gluten intolerance. In this editorial, we review recent progress in understanding CD in relation to its prevalence, diagnosis and possible mechanisms of pathogenesis. PMID:17451193

  12. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet.

  13. Celiac disease: From pathophysiology to treatment

    PubMed Central

    Parzanese, Ilaria; Qehajaj, Dorina; Patrinicola, Federica; Aralica, Merica; Chiriva-Internati, Maurizio; Stifter, Sanja; Elli, Luca; Grizzi, Fabio

    2017-01-01

    Celiac disease, also known as “celiac sprue”, is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac disease. PMID:28573065

  14. Diagnosis and Updates in Celiac Disease.

    PubMed

    Shannahan, Sarah; Leffler, Daniel A

    2017-01-01

    Celiac disease is an autoimmune disorder induced by gluten in genetically susceptible individuals. It can result in intraintestinal and extraintestinal manifestations of disease including diarrhea, weight loss, anemia, osteoporosis, or lymphoma. Diagnosis of celiac disease is made through initial serologic testing and then confirmed by histopathologic examination of duodenal biopsies. Generally celiac disease is a benign disorder with a good prognosis in those who adhere to a gluten-free diet. However, in refractory disease, complications may develop that warrant additional testing with more advanced radiologic and endoscopic methods. This article reviews the current strategy to diagnose celiac disease and the newer modalities to assess for associated complications. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Future therapeutic options for celiac disease.

    PubMed

    Sollid, Ludvig M; Khosla, Chaitan

    2005-03-01

    Celiac disease is a disorder of the small intestine caused by an inappropriate immune response to wheat gluten and similar proteins of barley and rye. At present, the only available treatment is a strict gluten-exclusion diet; hence the need for alternative treatments. Recent advances have improved our understanding of the molecular basis for this disorder and there are several attractive targets for new treatments. Oral enzyme supplementation is designed to accelerate gastrointestinal degradation of proline-rich gluten, especially its proteolytically stable antigenic peptides. Complementary strategies aiming to interfere with activation of gluten-reactive T cells include the inhibition of intestinal tissue transglutaminase activity to prevent selective deamidation of gluten peptides, and blocking the binding of gluten peptides to the HLA-DQ2 or HLA-DQ8 molecules. Other possible treatments include cytokine therapy, and selective adhesion molecule inhibitors that interfere with inflammatory reactions, some of which are already showing promise in the clinic for other gastrointestinal diseases.

  16. Implications of gluten exposure period, CD clinical forms, and HLA typing in the association between celiac disease and dental enamel defects in children. A case-control study.

    PubMed

    Majorana, Alessandra; Bardellini, Elena; Ravelli, Alberto; Plebani, Alessandro; Polimeni, Antonella; Campus, Guglielmo

    2010-03-01

    The association between coeliac disease (CD) and dental enamel defects (DED) is well known. The aim of this study was to investigate the prevalence of DED in children with CD and to specifically find the association of DED and gluten exposure period, CD clinical forms, HLA class II haplotype. This study was designed as a matched case-control study: 250 children were enrolled (125 coeliac children - 79 female and 46 male, 7.2 +/- 2.8 years and 125 healthy children). Data about age at CD diagnosis, CD clinical form, and HLA haplotype were recorded. Dental enamel defects were detected in 58 coeliac subjects (46.4%) against seven (5.6%) controls (P < 0.005). We found an association between DED and gluten exposure period, as among CD subjects the mean age at CD diagnosis was significantly (P = 0.0004) higher in the group with DED (3.41 +/- 1.27) than without DED (1.26 +/- 0.7). DED resulted more frequent (100%) in atypical and silent CD forms than in the typical one (30.93%). The presence of HLA DR 52-53 and DQ7antigens significantly increased the risk of DED (P = 0.0017) in coeliac children. Our results confirmed a possible correlation between HLA antigens and DED.

  17. Celiac Disease--What Parents and Caregivers Should Know

    ERIC Educational Resources Information Center

    Woodward, Alicia

    2011-01-01

    Celiac disease is a genetic autoimmune disorder characterized by a heightened sensitivity to gluten, the protein in wheat, barley and rye. The disease is more common than most people think, affecting approximately 3 million in the United States, about 1 in 100. One of the most notable things about celiac disease is that up to 97 percent of…

  18. Latest In vitro and in vivo models of celiac disease

    PubMed Central

    Stoven, Samantha; Murray, Joseph A.; Marietta, Eric V.

    2013-01-01

    Introduction Currently, the only treatment for celiac disease is a gluten free diet, and there is an increased desire for alternative therapies. In vitro and in vivo models of celiac disease have been generated in order to better understand the pathogenesis of celiac disease, and this review will discuss these models as well as the testing of alternative therapies using these models. Areas Covered The research discussed describes the different in vitro and in vivo models of celiac disease that currently exist and how they have contributed to our understanding of how gluten can stimulate both innate and adaptive immune responses in celiac patients. We also provide a summary on the alternative therapies that have been tested with these models and discuss whether subsequent clinical trials were done based on these tests done with these models of celiac disease. Expert Opinion Only a few of the alternative therapies that have been tested with animal models have gone on to clinical trials; however, those that did go on to clinical trial have provided promising results from a safety standpoint. Further trials are required to determine if some of these therapies may serve as an effective adjunct to a gluten free diet to alleviate the adverse affects associated with accidental gluten exposure. A “magic-bullet” approach may not be the answer to celiac disease, but possibly a future cocktail of these different therapeutics may allow celiac patients to consume an unrestricted diet. PMID:23293929

  19. Celiac Disease--What Parents and Caregivers Should Know

    ERIC Educational Resources Information Center

    Woodward, Alicia

    2011-01-01

    Celiac disease is a genetic autoimmune disorder characterized by a heightened sensitivity to gluten, the protein in wheat, barley and rye. The disease is more common than most people think, affecting approximately 3 million in the United States, about 1 in 100. One of the most notable things about celiac disease is that up to 97 percent of…

  20. The Gluten-Free Frenzy: Fad or Fitting?

    PubMed

    Johanson, Linda

    2015-01-01

    Although the gluten-free diet has been recognized as therapeutic for individuals suffering from celiac disease, it has been promoted recently for other indications, such as autism, chronic fatigue syn- drome, and irritable bowel syndrome, or simply as a healthy dietary choice for anyone. The basics of the gluten-free diet are explored, with evidence-based indications and nursing implications when patients choose gluten-free.

  1. Emerging Therapeutic Options for Celiac Disease

    PubMed Central

    Bakshi, Anita; Stephen, Sindu; Borum, Marie L.

    2012-01-01

    Celiac disease is an autoimmune disorder of the small intestine that is more common than was previously thought. This disease is caused by an inappropriate immune response to wheat gluten, barley, and rye. Three main pathways cause celiac disease: the environmental trigger (gluten), genetic susceptibility, and unusual gut permeability. The only treatment currently available is a strict gluten-free diet. Unfortunately, a majority of patients have difficulty complying with this diet, and the response to therapy is poor. Therefore, alternative treatments are being developed, and new insights into the pathophysiology of celiac disease have led to research into novel therapies. New treatments include engineering gluten-free grains, decreasing intestinal permeability by blockage of the epithelial zonulin receptor, inducing oral tolerance to gluten with a therapeutic vaccine, and degrading immunodominant gliadin peptides using probiotics with endopeptidases or transglutaminase inhibitors. These nondiet-based therapies provide hope for enhanced, lifelong celiac disease management with improved patient compliance and better quality of life. PMID:23483819

  2. Gluten Sensitivity

    MedlinePlus

    ... Medicamentos y La Dieta Sin Gluten Estilo de Vida Sin Gluten Comer en Restaurantes: Siete Consejos para ... Talk to your doctor to develop a treatment plan specific to you. I avoid wheat, but I ...

  3. Focus on Inclusive Education: The Educational and Social Challenges of Children with Celiac Disease: What Educators Should Know

    ERIC Educational Resources Information Center

    Chick, Kay A.

    2014-01-01

    Celiac disease is a genetic autoimmune disease in which gluten, a protein found in wheat, rye, barley, and contaminated oats, attacks the lining of the small intestine. Children with this disease must eliminate gluten from their diet. This article provides educators with essential information on celiac disease and the federal laws that protect the…

  4. Focus on Inclusive Education: The Educational and Social Challenges of Children with Celiac Disease: What Educators Should Know

    ERIC Educational Resources Information Center

    Chick, Kay A.

    2014-01-01

    Celiac disease is a genetic autoimmune disease in which gluten, a protein found in wheat, rye, barley, and contaminated oats, attacks the lining of the small intestine. Children with this disease must eliminate gluten from their diet. This article provides educators with essential information on celiac disease and the federal laws that protect the…

  5. Bone and Celiac Disease.

    PubMed

    Zanchetta, María Belén; Longobardi, Vanesa; Bai, Julio César

    2016-04-01

    More than 50% of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.

  6. Cutaneous manifestations in celiac disease

    PubMed Central

    Abenavoli, L; Proietti, I; Leggio, L; Ferrulli, A; Vonghia, L; Capizzi, R; Rotoli, M; Amerio, PL; Gasbarrini, G; Addolorato, G

    2006-01-01

    Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed. PMID:16521210

  7. Detoxification of gluten by means of enzymatic treatment.

    PubMed

    Wieser, Herbert; Koehler, Peter

    2012-01-01

    Celiac disease (CD) is an inflammatory disease of the upper small intestine in genetically predisposed individuals caused by glutamine- and proline-rich peptides from cereal storage proteins (gluten) with a minimal length of nine amino acids. Such peptides are insufficiently degraded by gastrointestinal enzymes; they permeate the lymphatic tissue, are bound to celiac-specific, antigen-presenting cells, and stimulate intestinal T-cells. The typical clinical pattern is a flat small intestinal mucosa and malabsorption. Currently, the only therapy is a strict, lifelong gluten-free diet. Recent research has shown that gluten and gluten peptides can be degraded by prolyl endopeptidases from different sources. These peptidases can either be used to produce gluten-free foods from gluten-containing raw materials, or they have been suggested as an oral therapy for CD, in which dietary gluten is hydrolyzed by coingested peptidases already in the stomach, thus preventing CD-specific immune reactions in the small intestine. This would be an alternative for CD patients to the gluten-free diet. Furthermore, microbial transglutaminase could be used to detoxify gluten either by selectively modifying glutamine residues of intact gluten by transamidation with lysine methyl ester or by crosslinking gluten peptides in beverages via isopeptide bonds so that they can be removed by filtration.

  8. Commercial assays to assess gluten content of gluten-free foods: why they are not created equal.

    PubMed

    Thompson, Tricia; Méndez, Enrique

    2008-10-01

    A standardized method of analysis is needed to quantitatively determine the gluten content of food and provide the basis for enforcing regulations regarding use of the term gluten-free in food labeling. People with celiac disease should feel confident that foods labeled "gluten-free" have been assessed for gluten using the same "best available" methodology. The Association of Analytical Communities and the Codex Alimentarius Commission endorse different methods. Both are used by manufacturers in the United States to determine the gluten-free status of food. The sandwich omega-gliadin enzyme-linked immunosorbent assay (ELISA) is the official method of the Association of Analytical Communities. It is able to quantify native and heated gluten. It is unable to accurately detect and quantify barley prolamins, can over- or underestimate gluten content, and cannot accurately quantify hydrolyzed gluten. The sandwich R5 ELISA was endorsed by Codex for gluten determination. It is able to quantify native and heated gluten. One criticism is that it overestimates barley hordein. It also is unable to accurately quantify hydrolyzed gluten. Foods that can be reliably assessed for gluten using a validated commercially available ELISA are those contaminated with native and heated proteins from wheat, barley, and rye. The degree of confidence that can be placed in a manufacturer's assertion that a product is gluten-free is based on the assay used to determine the gluten content and the specific food analyzed.

  9. Selenium in Gluten-free Products.

    PubMed

    Rybicka, Iga; Krawczyk, Magdalena; Stanisz, Ewa; Gliszczyńska-Świgło, Anna

    2015-06-01

    The nutritional value of gluten-free products is the subject of interest for food technologists and nutritionists, as the only effective treatment for celiac disease is a lifelong gluten-free diet. As selenium deficiencies in celiac disease are observed, the aim of the study was to determine the selenium content in 27 grain gluten-free products available on the European Union (EU) market. Moreover, selenium content in products based on popular gluten-free cereals like corn, rice, and buckwheat and in relatively new or less popular products based on oat, amaranth, teff, and quinoa was compared. Selenium content in the tested products ranged from 0.9 to 24.5 μg/100 g. The average content of selenium in products based on popular gluten-free cereals was 2.8 μg/100 g and in products based on oat, amaranth, teff, and quinoa was 10.8 μg/100 g. It indicates that products based on less popular grains, especially on oat, should be more frequently chosen as a source of selenium by people on gluten-free diet than traditionally consumed gluten-free grains.

  10. Celiac crisis is a rare but serious complication of celiac disease in adults

    PubMed Central

    Jamma, Shailaja; Rubio-Tapia, Alberto; Kelly, Ciaran P.; Murray, Joseph; Sheth, Sunil; Schuppan, Detlef; Dennis, Melinda; Leffler, Daniel A.

    2010-01-01

    Background & Aims Celiac crisis is a life-threatening syndrome in which patients with celiac disease have profuse diarrhea and severe metabolic disturbances. Celiac crisis is rare among adults and not well documented. To improve awareness of this condition and to facilitate diagnosis, we reviewed cases of celiac crisis to identify presenting features, formulate diagnostic criteria, and develop treatment strategies. Methods Cases of biopsy-proven celiac disease were reviewed. Celiac crisis was defined as acute onset or rapid progression of gastrointestinal symptoms that could be attributed to celiac disease and required hospitalization and/or parenteral nutrition, along with signs or symptoms of dehydration or malnutrition. Results Twelve patients met preset criteria for celiac crisis; 11 developed celiac crisis before they were diagnosed with celiac disease. Eleven patients had increased titres of tTG and 1 had immunoglobulin A deficiency. Results of biopsy analyses of duodenum samples from all patients were consistent with a Marsh 3 score (33% with total villous atrophy). Patients presented with severe dehydration, renal dysfunction, and electrolyte disturbances. All patients required hospitalization and intravenous fluids, 6 required corticosteroids, and 5 required parenteral nutrition. All patients eventually had a full response to a gluten-free diet. Conclusion Celiac crisis has a high morbidity and, although rarely described, occurs in adults and often has a clear precipitating factor. Patients that present with severe unexplained diarrhea and malabsorption should be tested for celiac disease; treatment with systemic steroids or oral budesonide should be considered. Nutritional support is often required in the short term but most patients ultimately respond to gluten avoidance. PMID:20417725

  11. Nonceliac gluten sensitivity: sense or sensibility?

    PubMed

    Di Sabatino, Antonio; Corazza, Gino Roberto

    2012-02-21

    Recent studies support the existence of a new condition, nonceliac gluten sensitivity, which manifests as intestinal or extraintestinal symptoms that improve or disappear after gluten withdrawal in individuals with normal small-bowel mucosa and negative results on serum antitransglutaminase and antiendomysial antibody testing. Although the clinical value of this concept is under debate, the prevalence of nonceliac gluten sensitivity in the general population is supposed to be many times higher than that of celiac disease. The lack of an unambiguous definition of nonceliac gluten sensitivity, a major pitfall, is primarily related to the heterogeneous cause of this condition, whose symptoms are presumed to be caused by different mechanisms. If nonceliac gluten sensitivity is an etiologically heterogeneous syndrome, then management options should vary according to the predominant or concomitant underlying pathogenic pathways.

  12. Celiac disease: an immune dysregulation syndrome.

    PubMed

    Levy, Joseph; Bernstein, Leora; Silber, Nicole

    2014-12-01

    Celiac disease is a chronic immune-mediated condition that develops in genetically predisposed individuals. It is characterized by the presence of circulating auto-antibodies in addition to an enteropathy and at times, other extra-intestinal manifestations triggered by exposure to the gliadin fraction of gluten, a family of proteins found in wheat, barley, and rye. There seems to be a rise in reported adverse reactions to gluten, an entity currently termed non-celiac gluten (or perhaps more accurately, wheat) sensitivity, where neither the enteropathy nor the auto-antibodies are present. Celiac disease has protean extra-intestinal manifestations, and an accurate diagnosis should be sought in people suffering from seemingly unrelated complaints, such as fatigue, anorexia, delayed puberty, short stature, decreased bone density, unusual skin rashes, unexplained iron deficiency, and infertility. The presence of an enteropathy, in conjunction with the positive serology, is considered the diagnostic gold standard for making the diagnosis of celiac disease. It is important to stress that the elimination of gluten, even in asymptomatic patients, brings about health benefits, particularly in relation to bone health, as well as a decrease in the incidence of small bowel malignancy, especially lymphoma. Better understanding of the pathophysiology of celiac disease and the molecular mechanisms involved in antigen recognition and processing has provided the impetus for the development of pharmacologic agents that might block the recognition of gluten and its conversion to a toxic antigenic target. Inhibition of tight junction dysregulation could also prevent or minimize the damage triggered by gluten. Work on genetically modified wheat cultivars has progressed, and the possibility of a vaccine to block the immune mediated trigger is being actively investigated. Education and guidance by a knowledgeable nutritionist or registered dietitian can go a long way in minimizing the

  13. Celiac disease. CME update for family physicians.

    PubMed Central

    Devlin, Shane M.; Andrews, Christopher N.; Beck, Paul L.

    2004-01-01

    OBJECTIVE: To review current understanding of the epidemiology, pathophysiology, diagnosis, and management of celiac disease. QUALITY OF EVIDENCE: Few recent randomized controlled trials (level I evidence) have studied treatments for celiac disease. There are recent comparative studies (level II evidence) and there is well established consensus (level III evidence) on diagnosis and treatment of celiac disease. MAIN MESSAGE: Celiac disease is an immune-mediated small bowel enteropathy caused by exposure to wheat gluten protein. The disease can be insidious and often presents with only subtle extraintestinal manifestations in a variety of organ systems. Recent epidemiologic surveys suggest celiac disease is much more common in North America than previously thought. Advances in immunology and screening have made diagnosis more reliable than in the past. Removing gluten from the diet is effective in most cases. CONCLUSION: Celiac disease manifests subtly and is an easy diagnosis to miss. Good laboratory screening tests and effective treatment are available. Family practitioners should consider celiac disease in patients who present with confounding symptoms. PMID:15171674

  14. Celiac disease and obstetrical-gynecological contribution

    PubMed Central

    Casella, Giovanni; Orfanotti, Guido; Giacomantonio, Loredana; Bella, Camillo Di; Crisafulli, Valentina; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio

    2016-01-01

    Celiac disease (CD) shows an increased prevalence in female, particularly during the fertile period. Celiac disease should be researched in infertility, spontaneous and recurrent abortions, delayed menarche, amenorrhea, early menopause, and children with low birth-weight. Celiac disease is still little considered during the evaluation of infertility. Up to 50% of women with untreated CD refer an experience of miscarriage or an unfavorable outcome of pregnancy. Celiac patients taking a normal diet (with gluten) have a shorter reproductive period. Women with undiagnosed CD had a higher risk of small for gestation age infants very small for gestational age infants and pre-term birth when compared with women with noted CD. The link between NCGS and infertility is actually unknown. The goal of our work is to perform an actual review about this topic and to increase the awareness in the medical population to research celiac disease in selected obstetric and gynecological disorders. PMID:27895849

  15. Celiac disease in African-Americans.

    PubMed

    Brar, Pardeep; Lee, Ann R; Lewis, Suzanne K; Bhagat, Govind; Green, Peter H R

    2006-05-01

    Celiac disease is generally under diagnosed in the United States and it is unclear whether the disease is encountered in ethnic minorities. Our purpose is to describe a case series of African-American patients with celiac disease. Nine (1.3%) African-American patients with celiac disease were identified from a prospectively generated database of 700 patients with biopsy proven celiac disease and seen between 1981 and 2004. Females predominated, with seven, compared to two males. Diarrhea was the presentation in only two patients, while three presented with iron deficiency anemia. One third had at least one autoimmune disease. Compliance with a gluten-free diet, the only medical therapy of this disease, was poor. Only four patients adhered strictly to the diet. Celiac disease occurs in African-Americans and may well be underdiagnosed. Special attention needs to be given to methods that encourage adherence to the diet in minority groups.

  16. Celiac Disease Presenting as Profound Diarrhea and Weight Loss – A Celiac Crisis

    PubMed Central

    Bul, Vadim; Sleesman, Brett; Boulay, Brian

    2016-01-01

    Patient: Male, 46 Final Diagnosis: Celiac crisis Symptoms: Abdominal pain • chronic diarrhea • lightheadedness • weakness • weight loss Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Celiac disease is a hypersensitivity enteropathy that can have various presentations in adults. Rarely, patients can present with severe lab abnormalities, dehydration and weight loss caused by celiac disease – a celiac crisis. Case Report: A 46-year-old male with a past medical history significant for diabetes mellitus, type 2 (DM2) and recently treated Bell’s Palsy presented to the emergency room complaining of weakness, diarrhea and lightheadedness. On presentation, the patient had a systolic blood pressure (SBP) of 60 mm Hg and a lactic acidosis with pH of 7.28. Infectious etiologies of diarrhea were ruled out. The patient had an EGD which showed erythema of the duodenal bulb. Serum anti-gliadin and anti-TTG IgA were both elevated suggesting Celiac disease. Biopsies showed histopathology consistent with celiac disease. The patient’s diarrhea resolved after initiation of a gluten free diet. He gained 25 kilograms after discharge and did not require further hospitalizations for diarrhea. Conclusions: Celiac crisis is a very rare presentation of celiac disease in adults but nonetheless should be considered in patients with marked metabolic derangements in the setting of osmotic diarrhea. Treatment consists of a gluten free diet and may require management with steroids and total parenteral nutrition (TPN). PMID:27492679

  17. Gut Microbiota and Celiac Disease.

    PubMed

    Marasco, Giovanni; Di Biase, Anna Rita; Schiumerini, Ramona; Eusebi, Leonardo Henry; Iughetti, Lorenzo; Ravaioli, Federico; Scaioli, Eleonora; Colecchia, Antonio; Festi, Davide

    2016-06-01

    Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.

  18. Celiac Disease

    MedlinePlus

    ... a group of proteins found in wheat, rye, barley, and grains derived from them or having different ... foods are gluten-free. Find alternatives to wheat, barley, and rye flours and other gluten-containing grain ...

  19. Symptomatic suspected gluten exposure is common among patients with coeliac disease on a gluten-free diet

    PubMed Central

    Silvester, Jocelyn A; Graff, Lesley A; Rigaux, Lisa; Walker, John R; Duerksen, Donald R

    2017-01-01

    BACKGROUND A gluten-free diet is the only recommended treatment for coeliac disease. AIM To determine the prevalence and characteristics of reactions to gluten among persons with coeliac disease on a gluten-free diet. METHODS Adults with biopsy proven, newly diagnosed coeliac disease were prospectively enrolled. A survey related to diet adherence and reactions to gluten was completed at study entry and 6 months. The Celiac Symptom Index (CSI), Celiac Diet Assessment Tool (CDAT) and Gluten-Free Eating Assessment Tool (GF-EAT) were used to measure coeliac disease symptoms and gluten-free diet adherence. RESULTS Of the 105 participants, 91% reported gluten exposure <1 per month and median CDAT score was 9 (IQR 8-11), consistent with adequate adherence. A suspected symptomatic reaction to gluten was reported by 66%. Gluten consumption was unsuspected until a reaction occurred (63%) or resulted from problems ordering in a restaurant (29%). The amount of gluten consumed ranged from cross-contact (30%) to a major ingredient (10%). Median time to symptom onset was 1 hour (range 10 min to 48 h), and median symptom duration was 24h (range 1 h to 8 days). Common symptoms included abdominal pain (80%), diarrhea (52%), fatigue (33%), headache (30%) and irritability (29%). CONCLUSION Reactions to suspected gluten exposure are common among patients with coeliac disease on a gluten-free diet. Eating at restaurants and other peoples’ homes remain a risk for unintentional gluten exposure. When following individuals with coeliac disease, clinicians should include questions regarding reactions to gluten as part of their assessment of gluten-free diet adherence. PMID:27443825

  20. Celiac Disease

    MedlinePlus

    ... be able to figure out which dishes at restaurants or friends' homes contain gluten. Some restaurants in your town might offer gluten-free dishes ... local support group may have a list of restaurants where the chef is familiar with the gluten- ...

  1. Gluten-Free Recipes

    MedlinePlus

    ... Vegetables 8 Public Recipe(s) 9 Member Only Recipe(s) Gluten-Free Recipes Recipes for traditional seasonal or holiday ... Treatment CSA Medications Position Olmesartan Frequently Asked Questions Gluten-Free Gluten Ataxia Gluten Ataxia Diagnosis Gluten Sensitivity ...

  2. Cold urticaria and celiac disease.

    PubMed

    Pedrosa Delgado, M; Martín Muñoz, F; Polanco Allué, I; Martín Esteban, M

    2008-01-01

    Cold urticaria can be associated with blood and thyroid disorders, drugs, or infections. Celiac disease is an autoimmune enteropathy caused by permanent gluten intolerance. It is often associated with other autoimmune diseases, such as chronic idiopathic urticaria. Nevertheless, association with cold urticaria has not yet been described. A boy aged 3 years 8 months presented local urticaria-angioedema when exposed to cold temperatures. An ice cube test was positive and iron deficiency anemia was demonstrated. He later developed legume intolerance, rhinoconjunctivitis related to pollen sensitization, and asthma. Due to persistence of cold urticaria symptoms and refractory anemia, a test for immunoglobulin A autoantibodies to tissue transglutaminase and an intestinal biopsy were performed. Results of both tests were compatible with celiac disease.A study of human leukocyte antigen indicated a high risk phenotype (HLA, DR6/DR7; DQA 0501, 0201; DQB 0301, 0201). After 7 months of a gluten-free diet, the boy's anemia resolved and he is free of symptoms when exposed to cold. This is a first description of the possibility of an association between celiac disease and cold urticaria. A poor course of cold urticaria in the absence of evidence of another underlying condition should lead to suspicion of celiac disease.

  3. [Nutritional assessment of gluten-free diet. Is gluten-free diet deficient in some nutrient?].

    PubMed

    Salazar Quero, J C; Espín Jaime, B; Rodríguez Martínez, A; Argüelles Martín, F; García Jiménez, R; Rubio Murillo, M; Pizarro Martín, A

    2015-07-01

    The gluten-free diet has traditionally been accepted as a healthy diet, but there are articles advocating that it may have some nutritional deficiencies. The current study assesses whether there was any change in the contributions of calories, essential elements, proportion of fatty acids, vitamins, minerals and fiber in children who were diagnosed with celiac diseases, comparing the diet with gluten prior one year after diagnosis with the diet without gluten to the year of diagnosis. The level of clinical or analytical impact that nutritional deficits could have was also assessed. A prospective,descriptive, observational study in which information was collected from a dietary survey, anthropometric and analytical data at pre-diagnosis of celiac disease and following a gluten diet and one year after celiac disease diagnosis, under gluten-free diet. A total of 37 patients meet the study criteria. A decrease in the intake of saturated fatty acids was found, with an increase of monounsaturated fatty acids and an increase in the intake of phosphorus in the diet without gluten. A deficient intake of vitamin D was found in both diets. Clinically, at year of gluten-free diet there was an improvement in weight and size. Analytically, there was an improvement in hemoglobin, ferritin, vitamin D, and parathyroid hormone in plasma. The gluten-free diet has minimal deficiencies, similar to those present in the diet with gluten, with an improvement in the lipid profile by increasing the proportion of monounsaturated fatty acids to the detriment of saturated fatty acids. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  4. Current and Emerging Therapy for Celiac Disease

    PubMed Central

    Makharia, Govind K.

    2014-01-01

    At present, strict and lifelong gluten-free diet is the only effective treatment for celiac disease. Even small amounts of gluten (50 mg/day) can be immunogenic; therefore all food and food items and drugs that contain gluten and its derivatives must be eliminated completely from the diet. While prescribing gluten-free diet is easy; the key to the success is the dietary counseling by a nutrition specialist and maintenance of adherence to GFD by the patient. In recent times, a number of targets to halt the process of immunological injury have been explored to find out alternative treatment for celiac disease. These targets include exploration of ancient wheat if they are less immunogenic, intra-luminal digestion of gluten using prolylendopeptidases, pretreatment of whole gluten with bacterial-derived peptidase before ingestion; prevention of passage of immunogenic peptides through the tight junctions such as zonulin antagonists, Blocking of HLA-DQ2 to prevent binding of immunogenic peptides, inhibition of transglutaminase 2, immune-modulation, and induction of tolerance to gluten using gluten tolerizing vaccines, use of gluten-sequestering polymers, use of anti-inflammatory drugs (glucocorticoids, budesonides) and anti-cytokines such as anti TNF-α, and anti-interleukin-15. While many of these targets are still in the pre-clinical phase, some of them including zonulin antagonist and endopeptidases have already reached phase II and phase III clinical trials. Furthermore, while these targets appear very exciting; they at best are likely to be used as adjunctive therapy rather than a complete replacement for gluten-free diet. PMID:25705619

  5. Current and emerging therapy for celiac disease.

    PubMed

    Makharia, Govind K

    2014-01-01

    At present, strict and lifelong gluten-free diet is the only effective treatment for celiac disease. Even small amounts of gluten (50 mg/day) can be immunogenic; therefore all food and food items and drugs that contain gluten and its derivatives must be eliminated completely from the diet. While prescribing gluten-free diet is easy; the key to the success is the dietary counseling by a nutrition specialist and maintenance of adherence to GFD by the patient. In recent times, a number of targets to halt the process of immunological injury have been explored to find out alternative treatment for celiac disease. These targets include exploration of ancient wheat if they are less immunogenic, intra-luminal digestion of gluten using prolylendopeptidases, pretreatment of whole gluten with bacterial-derived peptidase before ingestion; prevention of passage of immunogenic peptides through the tight junctions such as zonulin antagonists, Blocking of HLA-DQ2 to prevent binding of immunogenic peptides, inhibition of transglutaminase 2, immune-modulation, and induction of tolerance to gluten using gluten tolerizing vaccines, use of gluten-sequestering polymers, use of anti-inflammatory drugs (glucocorticoids, budesonides) and anti-cytokines such as anti TNF-α, and anti-interleukin-15. While many of these targets are still in the pre-clinical phase, some of them including zonulin antagonist and endopeptidases have already reached phase II and phase III clinical trials. Furthermore, while these targets appear very exciting; they at best are likely to be used as adjunctive therapy rather than a complete replacement for gluten-free diet.

  6. Review and practice guidelines for celiac disease in 2014.

    PubMed

    Nadhem, Omar N; Azeez, Ghassan; Smalligan, Roger D; Urban, Steven

    2015-04-01

    Celiac disease, or gluten-sensitive enteropathy, is defined as a state of heightened immunologic responsiveness to ingested gluten (from wheat, barley, or rye) in genetically susceptible individuals. Ingestion of the offending proteins leads to inflammation and intestinal mucosal damage, which may result in a spectrum of gastrointestinal symptoms, nutritional abnormalities, and systemic complications ranging from anemia and osteoporosis to secondary autoimmunity and malignancy. The genetic influence in the pathogenesis of celiac disease is indicated by its familial occurrence. Celiac disease does not develop unless a person has alleles that encode for human leukocyte antigen DQ2 or DQ8 proteins. The clinical picture of celiac disease has changed considerably during the past 30 years. Diarrhea, which was the presenting symptom in > 90% of celiac disease patients before 1981, is now the chief complaint in < 40%. In contrast, the increased frequency of atypical celiac disease presentations, including anemia and bone disease, is revealed by the widespread availability of serologic testing. An association between celiac disease and autoimmune disorders, such as type 1 diabetes, autoimmune thyroid disease, and Sjögren's syndrome, has been well documented. The tissue transglutaminase immunoglobulin antibody and the endomysial immunoglobulin antibody are the most sensitive and specific serologic tests, respectively, for identifying individuals who need to undergo an intestinal biopsy. If the suspicion of celiac disease is high, intestinal biopsy should be pursued even if serologic tests are negative. The gold standard for the diagnosis of celiac disease is a small bowel biopsy showing villous atrophy. The treatment for celiac disease is lifelong adherence to a gluten-free diet (GFD). Despite the proven benefits of the GFD, it can be exceedingly difficult to completely avoid gluten-containing foods, and adherence to a GFD is estimated to be only 45% to 80%.

  7. Prolyl endopeptidase-mediated destruction of T cell epitopes in whole gluten: chemical and immunological characterization.

    PubMed

    Marti, Thomas; Molberg, Oyvind; Li, Qing; Gray, Gary M; Khosla, Chaitan; Sollid, Ludvig M

    2005-01-01

    Celiac Sprue is a widely prevalent immune disease of the small intestine induced by dietary gluten intake in genetically susceptible individuals. It has been suggested that prolyl endopeptidases (PEPs) may be useful catalysts for gluten detoxification. We have investigated this hypothesis using food-grade gluten as the target antigen, and a combination of mass spectrometry and patient-derived T cells as quantitative assay systems. Spectrometric characterization of physiologically proteolyzed gluten revealed a number of 10 to 50 residue peptides containing known T cell epitopes involved in Celiac Sprue pathogenesis. Several of these peptides were multivalent, suggesting they may be potent triggers of the inflammatory response to gluten in celiac patients. Treatment of proteolyzed gluten with recombinant bacterial PEP decreased the number of potentially immunostimulatory peptides. Substantially reduced immunogenicity was also quantified in 12 of 14 intestinal polyclonal T cell lines from celiac patients. Kinetic investigations using eight T cell clones showed rapid destruction of alpha-gliadin epitopes, but less complete processing of gamma-gliadin epitopes. Given the difficulty associated with a strict lifelong gluten-exclusion diet, the ability of a single enzyme to greatly reduce the antigenic burden of grocery store gluten reinforces the case for developing oral peptidase therapy against Celiac Sprue.

  8. The adaptive immune response in celiac disease.

    PubMed

    Qiao, Shuo-Wang; Iversen, Rasmus; Ráki, Melinda; Sollid, Ludvig M

    2012-07-01

    Compared to other human leukocyte antigen (HLA)-associated diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, fundamental aspects of the pathogenesis in celiac disease are relatively well understood. This is mostly because the causative antigen in celiac disease-cereal gluten proteins-is known and the culprit HLA molecules are well defined. This has facilitated the dissection of the disease-relevant CD4+ T cells interacting with the disease-associated HLA molecules. In addition, celiac disease has distinct antibody responses to gluten and the autoantigen transglutaminase 2, which give strong handles to understand all sides of the adaptive immune response leading to disease. Here we review recent developments in the understanding of the role of T cells, B cells, and antigen-presenting cells in the pathogenic immune response of this instructive disorder.

  9. The present and the future in the diagnosis and management of celiac disease

    PubMed Central

    Castillo, Natalia E.; Theethira, Thimmaiah G.; Leffler, Daniel A.

    2015-01-01

    Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies—including gluten modification, modulation of intestinal permeability and immune response—could be central to the future treatment of celiac disease. PMID:25326000

  10. ACG clinical guidelines: diagnosis and management of celiac disease.

    PubMed

    Rubio-Tapia, Alberto; Hill, Ivor D; Kelly, Ciarán P; Calderwood, Audrey H; Murray, Joseph A

    2013-05-01

    This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in

  11. Dental Enamel Defects and Celiac Disease

    MedlinePlus

    ... Follow Us Home Health Information Digestive Diseases Dental Enamel Defects and Celiac Disease Related Topics Section Navigation Digestive Diseases Abdominal Adhesions Acid Reflux (GER & GERD) in Adults Definition & Facts ...

  12. Reduced-gliadin wheat bread: an alternative to the gluten-free diet for consumers suffering gluten-related pathologies.

    PubMed

    Gil-Humanes, Javier; Pistón, Fernando; Altamirano-Fortoul, Rossana; Real, Ana; Comino, Isabel; Sousa, Carolina; Rosell, Cristina M; Barro, Francisco

    2014-01-01

    Wheat flour cannot be tolerated by those who suffer allergies to gluten. Human pathologies associated with grain proteins have increased worldwide in recent years, and the only effective treatment available is a lifelong gluten-free diet, which is complicated to follow and detrimental to gut health. This manuscript describes the development of wheat bread potentially suitable for celiac patients and other gluten-intolerant individuals. We have made bread using wheat flour with very low content of the specific gluten proteins (near gliadin-free) that are the causal agents for pathologies such as celiac disease. Loaves were compared with normal wheat breads and rice bread. Organoleptic, nutritional, and immunotoxic properties were studied. The reduced-gliadin breads showed baking and sensory properties, and overall acceptance, similar to those of normal flour, but with up to 97% lower gliadin content. Moreover, the low-gliadin flour has improved nutritional properties since its lysine content is significantly higher than that of normal flour. Conservative estimates indicate that celiac patients could safely consume 67 grams of bread per day that is made with low-gliadin flour. However, additional studies, such as feeding trials with gluten-intolerant patients, are still needed in order to determine whether or not the product can be consumed by the general celiac population, as well as the actual tolerated amount that can be safely ingested. The results presented here offer a major opportunity to improve the quality of life for millions of sufferers of gluten intolerance throughout the world.

  13. Reduced-Gliadin Wheat Bread: An Alternative to the Gluten-Free Diet for Consumers Suffering Gluten-Related Pathologies

    PubMed Central

    Gil-Humanes, Javier; Pistón, Fernando; Altamirano-Fortoul, Rossana; Real, Ana; Comino, Isabel; Sousa, Carolina; Rosell, Cristina M.; Barro, Francisco

    2014-01-01

    Wheat flour cannot be tolerated by those who suffer allergies to gluten. Human pathologies associated with grain proteins have increased worldwide in recent years, and the only effective treatment available is a lifelong gluten-free diet, which is complicated to follow and detrimental to gut health. This manuscript describes the development of wheat bread potentially suitable for celiac patients and other gluten-intolerant individuals. We have made bread using wheat flour with very low content of the specific gluten proteins (near gliadin-free) that are the causal agents for pathologies such as celiac disease. Loaves were compared with normal wheat breads and rice bread. Organoleptic, nutritional, and immunotoxic properties were studied. The reduced-gliadin breads showed baking and sensory properties, and overall acceptance, similar to those of normal flour, but with up to 97% lower gliadin content. Moreover, the low-gliadin flour has improved nutritional properties since its lysine content is significantly higher than that of normal flour. Conservative estimates indicate that celiac patients could safely consume 67 grams of bread per day that is made with low-gliadin flour. However, additional studies, such as feeding trials with gluten-intolerant patients, are still needed in order to determine whether or not the product can be consumed by the general celiac population, as well as the actual tolerated amount that can be safely ingested. The results presented here offer a major opportunity to improve the quality of life for millions of sufferers of gluten intolerance throughout the world. PMID:24621595

  14. Prevalence of celiac disease in multiple sclerosis

    PubMed Central

    2011-01-01

    Background Celiac disease (CD) is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS) patients and their first-degree relatives. Methods We analyzed the prevalence of serological, histological and genetic CD markers in a series of 72 MS patients and in their 126 first-degree relatives, compared to 123 healthy controls. Results Tissue IgA-anti-transglutaminase-2 antibodies were positive in 7 MS patients (10%), compared to 3 healthy controls (2.4%) (p < 0.05). OR: 5.33 (CI-95%: 1.074-26.425). No differences were found in HLA-DQ2 markers between MS patients (29%) and controls (26%) (NS). We detected mild or moderate villous atrophy (Marsh III type) in duodenal biopsies, in 8 MS patients (11.1%). We also found a high proportion of CD among first-degree relatives: 23/126 (32%). Several associated diseases were detected, mainly dermatitis 41 (57%) and iron deficiency anemia in 28 (39%) MS patients. We also found in them, an increased frequency of circulating auto-antibodies such as anti-TPO in 19 (26%), ANA in 11 (15%) and AMA in 2 (3%). Conclusions We have found an increased prevalence of CD in 8 of the 72 MS patients (11.1%) and also in their first-degree relatives (23/126 [32%]). Therefore, increased efforts aimed at the early detection and dietary treatment of CD, among antibody-positive MS patients, are advisable. PMID:21385364

  15. Celiac Disease Presenting as Profound Diarrhea and Weight Loss - A Celiac Crisis.

    PubMed

    Bul, Vadim; Sleesman, Brett; Boulay, Brian

    2016-08-05

    BACKGROUND Celiac disease is a hypersensitivity enteropathy that can have various presentations in adults. Rarely, patients can present with severe lab abnormalities, dehydration and weight loss caused by celiac disease - a celiac crisis. CASE REPORT A 46-year-old male with a past medical history significant for diabetes mellitus, type 2 (DM2) and recently treated Bell's Palsy presented to the emergency room complaining of weakness, diarrhea and lightheadedness. On presentation, the patient had a systolic blood pressure (SBP) of 60 mm Hg and a lactic acidosis with pH of 7.28. Infectious etiologies of diarrhea were ruled out. The patient had an EGD which showed erythema of the duodenal bulb. Serum anti-gliadin and anti-TTG IgA were both elevated suggesting Celiac disease. Biopsies showed histopathology consistent with celiac disease. The patient's diarrhea resolved after initiation of a gluten free diet. He gained 25 kilograms after discharge and did not require further hospitalizations for diarrhea. CONCLUSIONS Celiac crisis is a very rare presentation of celiac disease in adults but nonetheless should be considered in patients with marked metabolic derangements in the setting of osmotic diarrhea. Treatment consists of a gluten free diet and may require management with steroids and total parenteral nutrition (TPN).

  16. Iron deficiency anemia in celiac disease.

    PubMed

    Freeman, Hugh James

    2015-08-21

    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.

  17. Iron deficiency anemia in celiac disease

    PubMed Central

    Freeman, Hugh James

    2015-01-01

    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet. PMID:26309349

  18. Celiac disease: pathogenesis and novel therapeutic strategies.

    PubMed

    Baldassarre, Mariella; Laneve, Anna Maria; Grosso, Roberto; Laforgia, Nicola

    2008-09-01

    Celiac disease is a digestive disease, considered as an autoimmune disorder, that damages the small intestine and interferes with absorption of nutrients. Individuals affected by celiac disease cannot tolerate a protein called gluten, present in wheat, rye, and barley, but also in other common products such as stamp and envelope adhesive, medicines, and vitamins. Celiac disease is a genetic condition that is triggered--or becomes active for the first time--after surgery, pregnancy, childbirth, viral infection, or severe emotional stress. Symptoms may occur in the digestive system, or in other parts of the body. Diagnosis involves blood tests and a biopsy of the small intestine. Recent findings estimate that about 2 million people in the United States have celiac disease, or about 1 in 133 people, as in Europe. Recent studies have shown that it may be more common in Africa, South America, and Asia than previously believed. The only treatment for celiac disease is to follow a gluten-free diet. Various other approaches are being studied that would reduce the need of dieting. One of those promising new approaches involves treating celiac patients with AT-1001, a paracellular permeability inhibitor, and with R-spondin1, a recombinant, secreted protein that early animal studies have shown to act as a highly specific stimulator of the gastrointestinal (GI) epithelial cells.

  19. Celiac crisis in adults: a case report and review of the literature focusing in the prevention of refeeding syndrome.

    PubMed

    de Almeida Menezes, Marcela; Cabral, Vírginia; Silva Lorena, Sônia Letícia

    2017-01-01

    Celiac crisis is a life-threatening complication of celiac disease that is rarely described in adults. We report the case of a 31-year-old man with celiac crisis as a first manifestation of celiac disease. The patient presented with severe diarrhea, metabolic acidosis, and electrolyte disturbances accompanied by electrocardiographic alterations. A satisfactory clinical response was obtained after the correction of electrolyte abnormalities, hydration, and nutritional support with a gluten-free diet according to recommendations for patients at high risk of refeeding syndrome. Celiac crisis generally occurs in patients with no previous diagnosis of celiac disease. The physician should therefore be aware of this diagnosis and consider celiac crisis in cases of unexplained intense secretory diarrhea, metabolic acidosis and severe electrolyte alterations in adults. The risk of refeeding syndrome should be assessed when a gluten-free diet is introduced and treatment of celiac crisis should include prevention and management of this possible complication.

  20. Clinical and diagnostic aspects of gluten related disorders.

    PubMed

    Tovoli, Francesco; Masi, Chiara; Guidetti, Elena; Negrini, Giulia; Paterini, Paola; Bolondi, Luigi

    2015-03-16

    Gluten is one of the most abundant and widely distributed components of food in many areas. It can be included in wheat, barley, rye, and grains such as oats, barley, spelt, kamut, and triticale. Gluten-containing grains are widely consumed; in particular, wheat is one of the world's primary sources of food, providing up to 50% of the caloric intake in both industrialized and developing countries. Until two decades ago, celiac disease (CD) and other gluten-related disorders were believed to be exceedingly rare outside of Europe and were relatively ignored by health professionals and the global media. In recent years, however, the discovery of important diagnostic and pathogenic milestones led CD from obscurity to global prominence. In addition, interestingly, people feeding themselves with gluten-free products greatly outnumber patients affected by CD, fuelling a global consumption of gluten-free foods with approximately $2.5 billion in United States sales each year. The acknowledgment of other medical conditions related to gluten that has arisen as health problems, providing a wide spectrum of gluten-related disorders. In February 2011, a new nomenclature for gluten-related disorders was created at a consensus conference in London. In this review, we analyse innovations in the field of research that emerged after the creation of the new classification, with particular attention to the new European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for CD and the most recent research about non-celiac gluten sensitivity.

  1. Optimizing the diagnosis of celiac disease.

    PubMed

    Lau, Michelle Shui Yee; Sanders, David S

    2017-05-01

    The diagnostic approach in celiac disease is continuously evolving as our understanding of its pathophysiology improves. This review aims to provide a summary of contemporary work that supports optimization of the diagnosis of this common yet underdiagnosed condition. The recently updated National Institute of Clinical Excellence and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines and the contentious biopsy-free diagnostic approach will be discussed. We will review the evidence advocating optimal biopsy techniques such as single bite biopsy and controversial bulb biopsy sampling to increase diagnostic yield. Recent data providing phenotypical characterization and clinical outcomes of celiac subtypes such as potential celiac disease, seronegative celiac disease and ultrashort celiac disease will be covered. We will present emerging evidence on novel case finding strategies with point of care tests. Promising novel markers for celiac disease such as serum intestinal fatty acid binding protein and in-vitro gluten challenge will be included. Recent work has demonstrated the clinical significance of the celiac disease subtypes, emphasizing the importance of careful diagnosis and recognition. There is a move toward a less invasive and perhaps more cost-effective diagnostic approach in celiac disease, but duodenal biopsy remains the gold standard at present for all adults and the majority of pediatric patients.

  2. Celiac disease in patients with Williams-Beuren syndrome.

    PubMed

    Mıhçı, Ercan; Nur, Banu Güzel; Berker-Karaüzüm, Sibel; Yılmaz, Aygen; Artan, Reha

    2015-01-01

    Celiac disease is an autoimmune, gastrointestinal disorder characterized by intolerance to the dietary grain protein gluten. An increased prevalence of celiac disease has been reported in Down syndrome and Turner syndrome, but there has been only few previous reports with respect to the association of celiac disease in Williams-Beuren syndrome. The aim of this study was to evaluate the frequency of celiac disease in our 24 Williams-Beuren syndrome patients. Gastrointestinal problems and celiac disease symptoms of patients were noted. All patients were analyzed by the titer of tissue transglutaminases IgA and IgG. HLA genotyping and intestinal biopsy was performed to the patients with positive serology. We also performed gluten free diet in the presence of compatible symptoms, serology, HLA genotyping and intestinal biopsy. In our study, two patients had positive tTG antibodies, but only one had positive biopsy finding for celiac disease. The frequency of celiac disease in patients with Williams-Beuren syndrome was estimated as 1/24 (4.1%). Though the number of participants in this study was limited, the results show that the frequency of celiac disease is higher in Williams-Beuren syndrome compared to the general population. We suggest that a high suspicion and testing for celiac disease should be recommended at certain intervals in all cases with Williams-Beuren syndrome to detect the cause of growth retardation and gastrointestinal problems.

  3. [The role of celiac disease and type 1 diabetes coexistance. Is celiac disease responsible for diabetic status?].

    PubMed

    Galicka-Latała, Danuta; Zwolińska-Wcisło, Małgorzata; Sosin-Rudnicka, Lucyna; Rozpondek, Piotr

    2009-01-01

    Celiac disease is the status of the autoimmune answer provoked by gluten ingestion in genetically predisposed people. Recently gluten entheropathy was considered as a rare clinical problem in adults. Celiac disease is an autoimmune disorder that can coexist with other diseases, such as diabetes mellitus type 1 (DMID), thyroid gland diseases. The aim of our study was evaluation of the frequency of coexistence of celiac disease with DMID using the level of anti tissue transglutaminase antibodies (IgA- tTG) and mucosal biopsy from the distal part of the duodenum. An attempt was made to estimate the influence of celiac disease on the intensity of clinical symptoms and metabolic balance in patients with DMID. Our study included 109 patients with DMID, aged 18-52 years. The frequency of the incidence of celiac disease in DMID patients was 9.71%. Gastric symptoms, such as diarrhea, abdominal pain were more frequent in patients with villous atrophy in the intestine. Hyperglycemia and problems with glucose balance in the serum were observed. Introduction of the gluten free diet led to improvement quality of life, less frequent hypoglycemic episodes and disappearance of diarrhea, increase of serum iron and decrease of IgA-tTG level in the serum. It is necessary to measure the level of IgA- tTG in patients with DMID. Diagnosis of celiac disease in patients with DMID and its treatment with gluten free diet causes the clinical, histological and biochemical improvement in these patients.

  4. Celiac disease: risk assessment, diagnosis, and monitoring.

    PubMed

    Setty, Mala; Hormaza, Leonardo; Guandalini, Stefano

    2008-01-01

    Celiac disease is an autoimmune disorder occurring in genetically susceptible individuals, triggered by gluten and related prolamins. Well identified haplotypes in the human leukocyte antigen (HLA) class II region (either DQ2 [DQA*0501-DQB*0201] or DQ8 [DQA*0301-DQB1*0302]) confer a large part of the genetic susceptibility to celiac disease.Celiac disease originates as a result of a combined action involving both adaptive and innate immunity. The adaptive immune response to gluten has been well described, with the identification of specific peptide sequences demonstrating HLA-DQ2 or -DQ8 restrictive binding motifs across various gluten proteins. As for innate immunity, through specific natural killer receptors expressed on their surface, intra-epithelial lymphocytes recognize nonclassical major histocompatibility complex (MHC)-I molecules such as MICA, which are induced on the surface of enterocytes by stress and inflammation, and this interaction leads to their activation to become lymphokine-activated killing cells. Four possible presentations of celiac disease are recognized: (i) typical, characterized mostly by gastrointestinal signs and symptoms; (ii) atypical or extraintestinal, where gastrointestinal signs/symptoms are minimal or absent and a number of other manifestations are present; (iii) silent, where the small intestinal mucosa is damaged and celiac disease autoimmunity can be detected by serology, but there are no symptoms; and, finally, (iv) latent, where individuals possess genetic compatibility with celiac disease and may also show positive autoimmune serology, that have a normal mucosa morphology and may or may not be symptomatic.The diagnosis of celiac disease still rests on the demonstration of changes in the histology of the small intestinal mucosa. The classic celiac lesion occurs in the proximal small intestine with histologic changes of villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytosis. Currently, serological

  5. Celiac Disease in The Netherlands: Demographic Data of Members of the Dutch Celiac Society.

    PubMed

    van Gils, Tom; Rootsaert, Bianca; Bouma, Gerd; Mulder, Chris J J

    2016-12-01

    Celiac disease is an autoimmune disease induced by the intake of gluten with a female to male ratio of 2-4:1. Female predominance has not been recognized in serological mass screening studies. Limited data are available on gender and age distribution in the daily clinical practice of celiac disease. The aim of this study is to describe differences in gender and age at the time of celiac disease diagnosis in the Netherlands. Data was obtained from a prospectively maintained database of members of the Dutch Celiac Society in whom celiac disease was diagnosed between 1980 and August 2015. retrospective database study; Setting: database of members of the Dutch Celiac Society; Participants: out of the total number of 26,986 current and ex-members, the data of 7,886 members could be used for analysis. Age at celiac disease diagnosis ranged between 0 and 88 years; the minority (36%) were diagnosed in childhood. In children, the majority (52%) were diagnosed before the age of 4 years. Median age did not differ in children when compared for gender (3 years). In adults, median age differed between males (52 years, IQR 41-61) and females (44 years, IQR 32-56), p<0.001. Female to male ratio was 2.4:1. The majority of celiac disease patients are diagnosed during adulthood, with males diagnosed at an older age. Only one-third of the patients were diagnosed at childhood. Celiac disease is less frequently diagnosed in young adult males.

  6. Preventing complications in celiac disease: our experience with managing adult celiac disease.

    PubMed

    Mulder, C J; Wierdsma, N J; Berkenpas, M; Jacobs, M A J M; Bouma, G

    2015-06-01

    Celiac disease is, as we know it, rather than being a rare and incurable disease until the 1950's, both quite common in screening studies and readily treatable. Three conditions are triggered by gluten consumption: celiac disease, the skin rash dermatitis herpetiformis and gluten ataxia. We describe our follow up for out clinic management, as evidence based data about such an approach are lacking in current literature. No food, beverages or medications containing any amount of gluten can be taken. Compliance is often difficult especially when patients are asymptomatic. We control a cohort, in daily practice, of over 700 adult patients. The majority of patients manage the diet without any problems. We describe our follow up in general, for serology, laboratory and histology. Forty percent of our newly diagnosed celiac patients do have a BMI over 25 kg/m(2). An appropriate attitude for this problem is lacking. The problem of slowly weaning off Dapsone over 5-10 years in DH is recognized. The bone density is checked in all newly diagnosed celiac patients. We control, if necessary, by telephone and lab controls done in local cities and see our patients only every two years face-to-face for follow up. The main question is if the adherence to a GFD, quality of life and prevention of complications is improved by visiting a dedicated celiac clinic. We hope to standardize this attitude on evidence data in the years to come. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Gluten screening of several dietary supplements by immunochromatographic assay.

    PubMed

    Oancea, Simona; Wagner, Adriana; Cîrstea, Elena; Sima, Mirela

    2011-01-01

    Celiac disease (CD) is a chronic intestinal disorder of public health concern caused by gluten ingestion in sensitive individuals. Gluten is a protein found not only in gluten-containing food but also as normal component of drugs and dietary supplements. Detection of gluten in dietary supplements is a very important task required for establishing their gluten status, which is highly important for the safety of products consumed by CD and gluten-sensitive patients. In this paper, we investigated the presence of gluten in twenty one common dietary supplements from the national market using the immunochromatographic assay. This visual assay proved to be an efficient rapid tool for gluten screening as an alternative to the ELISA techniques. The results have shown the presence of gluten in 23.8% of the investigated samples (vitamins, minerals, plant extracts, probiotics supplements, lactoferrin, propolis supplements). The results provide information which may contribute to the completion of the existing lists of gluten-free pharmaceuticals. It is known that for CD patients obtaining accurate information about the gluten content of a particular item is a difficult and time-consuming process.

  8. Mass spectrometry analysis of gliadins in celiac disease.

    PubMed

    Ferranti, Pasquale; Mamone, Gianfranco; Picariello, Gianluca; Addeo, Francesco

    2007-12-01

    In recent years, scientific research on wheat gluten proteins has followed three main directions aimed at (1) finding relationships between individual genetic alleles coding for gliadins, high or low molecular weight glutenin subunits, and the viscoelastic dough properties of flour-derived products such as pasta and bread; (2) identifying prolamins and derived peptides involved in celiac disease, a pathological condition in which the small intestine of genetically predisposed individuals is reversibly damaged; and (3) developing and validating sensitive and specific methods for detecting trace amounts of gluten proteins in gluten-free foods for celiac disease patients. In this review, the main aspects of current and perspective applications of mass spectrometry and proteomic technologies to the structural characterization of gliadins are presented, with focus on issues related to detection, identification, and quantification of intact gliadins, as well as gliadin-derived peptides relevant to the biochemical, immunological, and toxicological aspects of celiac disease.

  9. Psyllium as a substitute for gluten in bread.

    PubMed

    Zandonadi, Renata Puppin; Botelho, Raquel Braz Assunção; Araújo, Wilma Maria Coelho

    2009-10-01

    Celiac disease is an antibody-mediated enteropathy that presents permanent intolerance to ingested gluten. Currently, only one kind of treatment is available: the complete dietary elimination of all sources of gluten. The aim of the present study was to evaluate the effect of replacing gluten with psyllium on sensory characteristics of bread dough and to compare the chemical, nutritional, technological, and sensory characteristics of the modified preparations. This study is experimental and was subdivided into five steps: selection and development of preparation, chemical analysis, sensory analysis, and statistical analysis. Modified samples of the bread dough achieved a 93.0% acceptance rate for individuals with celiac disease and up to 97.0% for individuals without celiac disease. The most affected characteristics were odor and texture. In terms of chemical composition of the bread dough, energy was reduced by 32.1% and the fat fraction was 42.3% before being cooked. Data obtained from sensory analysis of psyllium doughs indicate that the products had good acceptance by individuals with celiac disease as well as by individuals without celiac disease. This suggests that psyllium can replace gluten in preparations. Furthermore, in terms of chemical composition, products made with modified dough had less fat and fewer calories.

  10. Novel Monoclonal Antibody-Based Immunodiagnostic Assay for Rapid Detection of Deamidated Gluten Residues.

    PubMed

    Masiri, Jongkit; Benoit, Lora; Katepalli, Madhu; Meshgi, Mahzad; Cox, David; Nadala, Cesar; Sung, Shao-Lei; Samadpour, Mansour

    2016-05-11

    Gluten derived from wheat and related Triticeae can induce gluten sensitivity as well as celiac disease. Consequently, gluten content in foods labeled "gluten-free" is regulated. Determination of potential contamination in such foods is achieved using immunoassays based on monoclonal antibodies (mAbs) that recognize specific epitopes present in gluten. However, food-processing measures can affect epitope recognition. In particular, preparation of wheat protein isolate through deamidation of glutamine residues significantly limits the ability of commercial gluten testing kits in their ability to recognize gluten. Adding to this concern, evidence suggests that deamidated gluten imparts more pathogenic potential in celiac disease than native gluten. To address the heightened need for antibody-based tools that can recognize deamidated gluten, we have generated a novel mAb, 2B9, and subsequently developed it as a rapid lateral flow immunoassay. Herein, we report the ability of the 2B9-based lateral flow device (LFD) to detect gluten from wheat, barley, and rye and deamidated gluten down to 2 ppm in food as well as its performance in food testing.

  11. Burning Tongue as Initial Presentation of Celiac Disease in an Elderly Woman: A Case Report.

    PubMed

    Sherman, Andrea; Zamulko, Alla

    2016-06-01

    There are few reports in the literature where celiac disease presents with tongue manifestations, although atypical presentations of celiac disease are not uncommon. This case report highlights an atypical presentation of celiac disease in an elderly female. Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Complete symptom improvement was noted by 10 weeks into the initiation of a gluten free diet. Celiac disease can present at any age and should be considered as a differential in findings of malabsorption and gastrointestinal symptoms.

  12. [Celiac disease : Pathogenesis, clinics, epidemiology, diagnostics, therapy].

    PubMed

    Schuppan, Detlef

    2016-07-01

    Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non-infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T‑cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80-90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T‑cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development.

  13. Love and Life without Gluten | NIH MedlinePlus the Magazine

    MedlinePlus

    ... with celiac disease. It turns out that most pasta is primarily made with gluten. He was surprised to learn that there was only one treatment: Jack had to follow a strict gluten-free diet. “There isn’t really anything you can ...

  14. Evaluation of commercial gluten-free foods from the Brazilian market

    USDA-ARS?s Scientific Manuscript database

    In addition to Celiac Disease, there are other gluten related disorders classified according to immunological response, e.g. autoimmune, allergic and sensitivity (non-autoimmune and non-allergic). In all cases, the only effective therapy is strict adherence to a gluten free diet, which consists of a...

  15. Characterization of Antibodies for Grain-Specific Gluten Detection.

    PubMed

    Sharma, Girdhari M; Rallabhandi, Prasad; Williams, Kristina M; Pahlavan, Autusa

    2016-03-01

    Gluten ingestion causes immunoglobulin E (IgE)-mediated allergy or celiac disease in sensitive individuals, and a strict gluten-free diet greatly limits food choices. Immunoassays such as enzyme-linked immunosorbent assay (ELISA) are used to quantify gluten to ensure labeling compliance of gluten-free foods. Anti-gluten antibodies may not exhibit equal affinity to gluten from wheat, rye, and barley. Moreover, because wheat gluten is commonly used as a calibrator in ELISA, accurate gluten quantitation from rye and barley contaminated foods may be compromised. Immunoassays utilizing grain-specific antibodies and calibrators may help improve gluten quantitation. In this study, polyclonal antibodies raised against gluten-containing grain-specific peptides were characterized for their immunoreactivity to gluten from different grain sources. Strong immunoreactivity to multiple gluten polypeptides from wheat, rye, and barley was observed in the range 34 to 43 kDa with anti-gliadin, 11 to 15 and 72 to 95 kDa with anti-secalin, and 30 to 43 kDa with anti-hordein peptide antibodies, respectively. Minimal or no cross-reactivity with gluten from other grains was observed among these antibodies. The anti-consensus peptide antibody raised against a repetitive amino acid sequence of proline and glutamine exhibited immunoreactivity to gluten from wheat, rye, barley, and oat. The antibodies exhibited similar immunoreactivity with most of the corresponding grain cultivars by ELISA. The high specificity and minimal cross-reactivity of grain-specific antibodies suggest their potential use in immunoassays for accurate gluten quantitation.

  16. Why is celiac disease so common in Ireland?

    PubMed

    Cronin, C C; Shanahan, F

    2001-01-01

    Celiac disease (gluten sensitive enteropathy) is a condition affecting the small bowel, characterized by permanent intolerance to dietary gluten, and giving rise to varying degrees of malabsorption and diarrhea. With the advent of sensitive screening tests, the condition is being increasingly diagnosed. Celiac disease is more common in the Irish and in those of Irish descent. Simoons (1978, 1981) hypothesized that the present-day prevalence of celiac disease across Europe is related to the interaction between genetic gradients, largely determined by the advance of agriculture, and historical patterns of cereal ingestion. This essay examines Simoons' hypothesis as it relates to Ireland, reviews the ethnic and genetic mix of those living on the island of Ireland and aspects of Irish dietary history, and considers how these factors may have combined to result in a high frequency of celiac disease.

  17. Association between celiac disease and chronic hepatitis C

    PubMed Central

    Casella, Giovanni; Viganò, Davide; Romano Settanni, Carlo; Morelli, Olivia; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio

    2016-01-01

    Celiac disease is characterized by a gluten-induced damage of the small bowel in sensitive individuals that may cause malabsorption. Non-intestinal inflammatory diseases may trigger immunologic gluten intolerance in susceptible people and the HCV virus may be considered as a suitable candidate. Interferon therapy could precipitate symptom onset in subjects with silent celiac disease. In fact, symptoms such as diarrhea, anemia, and weight loss may occur during interferon therapy and are associated with serological positivity of anti-tranglutaminase antibodies. To date, considering the available literature data, it is very difficult to support a firm association between HCV chronic hepatitis and celiac disease. Thus, such a serological screening in HCV patients before starting interferon therapy should not be recommended. However, serology for celiac disease must be considered in patients who develop diarrhea and/or weight loss during such therapy. PMID:27458507

  18. Self-Reported Prevalence of Gluten-Related Disorders and Adherence to Gluten-Free Diet in Colombian Adult Population

    PubMed Central

    Franco-Aguilar, Alejandro; Magaña-Ordorica, Dalia

    2016-01-01

    Background. Celiac disease seems to be rare in Colombians, but there are currently no data about the prevalence rates of symptomatic adverse reactions to gluten or adherence to gluten-free diet (GFD) in this population. Aim. to evaluate the self-reported prevalence rates of adverse reactions to gluten, adherence to GFD, and gluten-related disorders at population level in Colombia. Methods. A self-administered questionnaire-based cross-sectional study was conducted in a population from Northwest Colombia. Results. The estimated prevalence rates were (95% CI) 7.9% (6.5–9.6) and 5.3% (4.1–6.7) for adverse and recurrent adverse reactions to wheat/gluten, respectively, adherence to GFD 5.9% (4.7–7.4), wheat allergy 0.74% (0.3–1.4), and nonceliac gluten sensitivity 4.5% (3.5–5.8). There were no self-reported cases of celiac disease. Prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.41% (0.17–0.96). Most respondents reported adherence to GFD without a physician-diagnosis of gluten-related disorders (97.2%). The proportion of gluten avoiders was 17.2% (15.2–19.5). Most of them did not report recurrent adverse reactions to wheat/gluten (87.0%). Conclusions. Nonceliac gluten sensitivity is rarely formally diagnosed in Colombia, but this population has the highest prevalence rate of adherence to GFD reported to date. Consequently, most respondents were avoiding wheat- and/or gluten-based products for reasons other than health-related symptoms. PMID:27648068

  19. A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties

    PubMed Central

    Martin, Edith; Bethune, Michael T.; Gray, Gary M.; Khosla, Chaitan

    2009-01-01

    Background and Aims Celiac sprue is a life-long disease characterized by an intestinal inflammatory response to dietary gluten. A gluten-free diet is an effective treatment for most patients, but accidental ingestion of gluten is common, leading to incomplete recovery or relapse. Food-grade proteases capable of detoxifying moderate quantities of dietary gluten could mitigate this problem. Methods We evaluated the gluten detoxification properties of two food-grade enzymes, aspergillopepsin (ASP) from Aspergillus niger and dipeptidyl peptidase IV (DPPIV) from Aspergillus oryzae. The ability of each enzyme to hydrolyze gluten was tested against synthetic gluten peptides, a recombinant gluten protein, and simulated gastric digests of whole gluten and whole-wheat bread. Reaction products were analyzed by mass spectrometry, HPLC, ELISA with a monoclonal antibody that recognizes an immunodominant gluten epitope, and a T cell proliferation assay. Results ASP markedly enhanced gluten digestion relative to pepsin, and cleaved recombinant α2-gliadin at multiple sites in a non-specific manner. When used alone, neither ASP nor DPPIV efficiently cleaved synthetic immunotoxic gluten peptides. This lack of specificity for gluten was especially evident in the presence of casein, a competing dietary protein. However, supplementation of ASP with DPPIV enabled detoxification of moderate amounts of gluten in the presence of excess casein and in whole-wheat bread. ASP was also effective at enhancing the gluten-detoxifying efficacy of cysteine endoprotease EP-B2 under simulated gastric conditions. Conclusions Clinical studies are warranted to evaluate whether a fixed dose ratio combination of ASP and DPPIV can provide near-term relief for celiac patients suffering from inadvertent gluten exposure. Due to its markedly greater hydrolytic activity against gluten than endogenous pepsin, food-grade ASP may also augment the activity of therapeutically relevant doses of glutenases such as EP

  20. Self-rated quality of life in celiac disease.

    PubMed

    Ciacci, C; D'Agate, C; De Rosa, A; Franzese, C; Errichiello, S; Gasperi, V; Pardi, A; Quagliata, D; Visentini, S; Greco, L

    2003-11-01

    As much as 1% of the gluten-consuming world is gluten-intolerant. New screening methods are increasingly identifying gluten intolerance in individuals previously free from health problems. The often-abrupt major change in diet may adversely affect the patient's quality of life. Our aim was to evaluate self-perceived quality of life in a large cohort of adult celiac patients after at least one year of a gluten-free diet. In all 581 members (410 females) of five regional celiac societies were on a gluten-free regimen for at least one year. In this cross-sectional study, a modified version of the Zung Self-Rating Depression Scale was administered to the 581 patients from five Italian regions. Most patients correctly defined celiac disease, and compliance with the gluten-free diet was high, although reporting bias cannot be excluded. Most felt well (83.6% "very well" and "well"); consequently, anxiety and depression scores were low. Happiness also scored low. Most participants did not feel that a gluten-free life differentiated them from the general population. Women and patients diagnosed after 20 years of age had better dietary compliance, but more problems in their social life. Happiness scores were higher in patients diagnosed before 20 years of age. Anxiety and depression were infrequent in this group; however, anxiety was frequently related to feeling different from the general population, and depression to an unsatisfactory sexual life. In conclusion, celiac disease does not appear to be associated to a low level of self-perceived quality of life in members of the Italian Celiac Society.

  1. Introduction of oats in the diet of individuals with celiac disease: a systematic review.

    PubMed

    Pulido, Olga M; Gillespie, Zoe; Zarkadas, Marion; Dubois, Sheila; Vavasour, Elizabeth; Rashid, Mohsin; Switzer, Connie; Godefroy, Samuel Benrejeb

    2009-01-01

    Celiac disease is an immune-mediated disease, triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. The only treatment for celiac disease is a strict gluten-free diet for life. This paper presents a systematic review of the scientific literature on the safety of pure oats for individuals with celiac disease, which historically has been subject to debate. Limitations identified within the scientific database include: limited data on long-term consumption, limited numbers of participants in challenge studies, and limited reporting about the reasons for withdrawals from study protocols. Furthermore, some evidence suggests that a small number of individuals with celiac disease may be intolerant to pure oats and some evidence from in vitro studies suggests that an immunological response to oat avenins can occur in the absence of clinical manifestations of celiac disease as well as suggesting that oat cultivars vary in toxicity. Based on the majority of the evidence provided in the scientific database, and despite the limitations, Health Canada and the Canadian Celiac Association (CCA) concluded that the majority of people with celiac disease can tolerate moderate amounts of pure oats. The incorporation of oats into a gluten-free diet provides high fiber and vitamin B content, increased palatability, and beneficial effects on cardiovascular health. However, it is recommended that individuals with celiac disease should have both initial and long-term assessments by a health professional when introducing pure oats into a gluten-free diet.

  2. The surface-associated proteins of wheat starch granules: suitability of wheat starch for celiac patients

    USDA-ARS?s Scientific Manuscript database

    Wheat starch is used to make baked products for celiac patients in several European countries, but is avoided in the US because of uncertainty about the amounts of associated grain storage (gluten) proteins. People with celiac disease (CD) must avoid wheat, rye and barley proteins and products that...

  3. Celiac disease: epidemiology, pathogenesis, diagnosis, and nutritional management.

    PubMed

    Schuppan, Detlef; Dennis, Melinda D; Kelly, Ciaran P

    2005-01-01

    Celiac disease (CD) is an inflammatory small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. It is triggered by the gluten proteins of wheat, barley, and rye. All patients express the antigen-presenting molecules human leukocyte antigen-DQ2 (HLA-DQ2) and/or HLA-DQ8, which bind gluten peptides and thus activate destructive intestinal T cells. Patients with untreated CD have circulating IgA autoantibodies to the enzyme tissue transglutaminase (tTG), a component of endomysium. Testing for serum IgA tTG has a high predictive value. Therapy of CD is a lifelong gluten-free diet. Counseling by an expert dietitian and association with a celiac support group are important in helping the patient embark on a healthy gluten-free diet. Current research focuses on non-dietary therapies and treatment of refractory (diet-unresponsive) CD.

  4. Review Article: Celiac Disease, New Approaches to Therapy

    PubMed Central

    Rashtak, Shahrooz; Murray, Joseph A

    2014-01-01

    STRUCTURED SUMMARY Background Celiac disease is managed by life-long gluten withdrawal from the diet. However strict adherence to a gluten-free diet is difficult and is not always effective. Novel therapeutic approaches are needed to supplement or even replace the dietary treatment. Aims To review recent advances in new therapeutic options for celiac disease. Methods A literature search was performed on MEDLINE, EMBASE, Web of Science, Scopus, DDW.org and ClinicalTrial.gov for English articles and abstracts. The search terms used include but not limited to “Celiac disease”, “new”, “novel”, Advances”, “alternatives” and “Drug therapy”. The cited articles were selected based on the relevancy to the review objective. Results Several new therapeutic approaches for celiac disease are currently under development by targeting its underlying pathogenesis. Alternative therapies range from reproduction of harmless wheat strains to immunomodulatory approaches. Some of these therapies such as enzymatic cleavage of gluten and permeability inhibitors have shown promise in clinical studies. Conclusion Gluten-free diet is still the only practical treatment for patients with celiac disease. Novel strategies provide promise of alternative adjunctive approaches to diet restriction alone for patients with this disorder. PMID:22324389

  5. Gluten Intake Is Positively Associated with Plasma α2-Macroglobulin in Young Adults.

    PubMed

    Jamnik, Joseph; García-Bailo, Bibiana; Borchers, Christoph H; El-Sohemy, Ahmed

    2015-06-01

    Gluten-free foods have increased in popularity over the past decade and are now being consumed by individuals without celiac disease. However, the physiologic effects of gluten intake in individuals without celiac disease remain unknown. High-abundance plasma proteins involved in inflammation, endothelial function, and other physiologic pathways may represent potential biomarkers of biological effects of gluten intake. The objective was to examine the association between gluten intake and plasma proteomic biomarkers in a population of adults without clinically diagnosed celiac disease. Subjects (n = 1095) were participants of the Toronto Nutrigenomics and Health Study, a cross-sectional examination of young adults aged 20-29 y. Dietary gluten intake was estimated by using a 1-mo, 196-item semiquantitative food-frequency questionnaire. The concentrations of 54 plasma proteins were measured simultaneously by liquid chromatography/multiple-reaction monitoring mass spectrometry. The association between gluten intake and each proteomic biomarker was examined by using general linear models. Analyses were then conducted in individuals who do not have the human leukocyte antigen (HLA)-DQ2 or DQ8 risk variants required for the development of celiac disease to determine whether any associations observed could have been due to undiagnosed cases of celiac disease. Increased gluten intake was associated with increased concentrations of plasma α2-macroglobulin (P = 0.01), a marker of inflammation and cytokine release. The association remained after adjusting for age, sex, BMI, ethnicity, physical activity, energy intake, fiber intake, and hormonal contraceptive use among women. This relation was not modified by HLA risk variants. Gluten consumption is associated with increased plasma α2-macroglobulin in young adults, which appears to be independent of celiac disease, suggesting possible effects of gluten on inflammation. © 2015 American Society for Nutrition.

  6. Prospects of Developing Medicinal Therapeutic Strategies and Pharmaceutical Design for Effective Gluten Intolerance Treatment.

    PubMed

    Savvateeva, Lyudmila V; Zamyatnin, Andrey A

    2016-01-01

    Gluten intolerance is an umbrella term for gluten-related disorders manifested in health decline as a result of the gluten ingestion. The spectrum of gluten-related disorders includes three major groups: autoimmune (mainly, Celiac Disease, CD, also known as Celiac Sprue, dermatitis herpetiformis, or gluten-sensitive ataxia), allergic (wheat allergy, WA), and non-autoimmune non-allergic (non-celiac gluten sensitivity, NCGS, or gluten sensitivity, GS). Pathogenesis and diagnostics of CD and WA are well established in contrast to NCGS, pathogenicity of which is still poorly understood and its symptoms are frequently misdiagnosed since most of the NCGS cases are currently identified via the process of CD and WA exclusion. By now, the only one proven effective way for CD treatment is gluten-free diet (GFD). However, such an increasingly gaining popularity diet is apparently unsuitable for NCGS treatment because in this case gluten does not always arise as the major or exclusive culprit of gastrointestinal disorder. Furthermore, it is some physicians' opinion that GFD can be deficient in fiber and in other vitamins and minerals. In many cases, GFD is commercially inaccessible for the most needy, whereas strict adherence to the diet is complicated by the presence of small amounts of the gluten components in some foods and even medicines. In this regard, a number of research groups and pharmaceutical companies are extensively developing alternative medicinal approaches to GFD for effective gluten intolerance treatment. This review summarizes our understanding of gluten-related disorders, possible mechanisms of gluten intolerance activation and advantages of gluten intolerance medicinal treatment using novel drug candidates obtained with a proper pharmaceutical design.

  7. Heart transplantation in rapidly progressive end-stage heart failure associated with celiac disease

    PubMed Central

    Barrio, Juan P; Cura, Geraldine; Ramallo, German; Diez, Mirta; Vigliano, Carlos A; Katus, Hugo A; Mereles, Derliz

    2011-01-01

    Celiac disease is characterised by chronic immune-mediated malabsorption in genetically susceptible individuals induced by gluten proteins present in wheat, barley and rye. It occurs in adults and children at rates approaching 1% of the population. Cardiomyopathy associated with celiac disease is infrequent. The authors present here a first case of a severe progressive dilated cardiomyopathy that required heart transplantation in young woman with celiac disease. PMID:22696747

  8. Psychosis and Silent Celiac Disease in a Down Syndrome Adolescent: A Case Report

    PubMed Central

    Morant, Amparo

    2011-01-01