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  1. Celiac Disease

    MedlinePlus

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

  2. Celiac Disease

    MedlinePlus

    ... small intestine. People with celiac disease cannot eat gluten, a protein found in wheat, barley, and rye. ... Disease Doctors treat celiac disease by prescribing a gluten-free diet. Symptoms significantly improve for most people ...

  3. Celiac disease.

    PubMed

    Rivera, E; Assiri, A; Guandalini, S

    2013-10-01

    Celiac disease, with a prevalence around 1% of the general population, is the most common genetically-induced food intolerance in the world. Triggered by the ingestion of gluten in genetically predisposed individuals, this enteropathy may appear at any age, and is characterized by a wide variety of clinical signs and symptoms. Among them, gastrointestinal presentations include chronic diarrhea, abdominal pain, weight loss or failure to thrive in children; but extra-intestinal manifestations are also common, and actually appear to be on the rise. They include a large variety of ailments, such as dermatitis Herpetiformis, anemia, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminases, and even female infertility. For the clinician interested in oral diseases, celiac disease can lead to delayed tooth eruption, dental enamel hypoplasia, recurrent oral aphthae. Diagnosing celiac disease requires therefore a high degree of suspicion followed by a very sensitive screening test: serum levels of the autoantibody anti-tissue transglutaminase. A positive subject will then be confirmed by an intestinal biopsy, and will then be put on a strict gluten-free diet, that in most cases will bring a marked improvement of symptoms. Newer forms of treatment which in the future will probably be available to the non-responsive patients are currently being actively pursued. PMID:23496382

  4. 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 ...

  5. Celiac disease.

    PubMed

    Green, Peter H R; Lebwohl, Benjamin; Greywoode, Ruby

    2015-05-01

    This review will focus on the pathogenesis, clinical manifestations, diagnosis, and management of celiac disease (CD). Given an increasing awareness of gluten-related disorders, medical professionals of all varieties are encountering patients with a diagnosis of CD or who are thought to have food intolerance to gluten. The prevalence of CD among the general population is estimated to be 1% in Western nations, and there is growing evidence for underdiagnosis of the disease, especially in non-Western nations that were traditionally believed to be unaffected. The development of serologic markers specific to CD has revolutionized the ability both to diagnose and monitor patients with the disease. Additionally, understanding of the clinical presentations of CD has undergone a major shift over the past half century. Although it is well understood that CD develops in genetically predisposed subjects exposed to gluten, the extent of other environmental factors in the pathogenesis of the disease is an area of continued research. Currently, the main therapeutic intervention for CD is a gluten-free diet; however, novel nondietary agents are under active investigation. Future areas of research should also help us understand the relationship of CD to other gluten-related disorders.

  6. Celiac Disease

    PubMed Central

    Rubio-Tapia, Alberto; Murray, Joseph A

    2010-01-01

    Purpose of review To summarize recent advances in celiac disease (CD) published between August 2008 and July 2009. Recent findings CD affects ~1% of most populations but remains largely unrecognized. In the last year, work has shown that the prevalence of CD has increased dramatically, not simply due to increased detection. Also, undiagnosed CD may be associated with increased mortality. Significant progress has been made in understanding how gliadin peptides can cross the intestinal border and access the immune system. New genetic loci and candidate genes that may contribute to the risk of CD and its overlap with type 1 diabetes mellitus have been identified. New deamidated gliadin peptides antibodies have better diagnostic accuracy over native gliadin-based tests. The inclusion of duodenal bulb biopsy specimens may increase the rate of CD detection. The spectrum of CD likely includes a minority of patients with mild enteropathy. A practical 7-item instrument may facilitate standardized evaluation of gluten-free diet adherence. Finally, refractory CD, whilst rare, is associated with a poor prognosis. Summary Celiac disease is a global health problem that requires a multidisciplinary and increasingly cooperative multinational research effort. PMID:20040864

  7. Treatment of Celiac Disease

    MedlinePlus

    ... Mission Statement Press Releases 2015 CSA Youth Ambassador PEER Grants Awarded Bountiful Pantry DNI Group, LLC Earth ... for Celiac Disease International Symposium Celiac Disease 2013 Peer Review Research Application History of Gluten Induced Diseases ...

  8. Celiac disease - sprue

    MedlinePlus

    Sprue; Nontropical sprue; Gluten intolerance; Gluten-sensitive enteropathy; Gluten-free diet celiac disease ... When people with celiac disease eat foods with gluten, their immune system reacts by damaging the villi. ...

  9. Celiac Disease: Diagnosis.

    PubMed

    Byrne, Greg; Feighery, Conleth F

    2015-01-01

    Historically the diagnosis of celiac disease has relied upon clinical, serological, and histological evidence. In recent years the use of sensitive serological methods has meant an increase in the diagnosis of celiac disease. The heterogeneous nature of the disorder presents a challenge in the study and diagnosis of the disease with patients varying from subclinical or latent disease to patients with overt symptoms. Furthermore the related gluten-sensitive disease dermatitis herpetiformis, while distinct in some respects, shares clinical and serological features with celiac disease. Here we summarize current best practice for the diagnosis of celiac disease and briefly discuss newer approaches. The advent of next-generation assays for diagnosis and newer clinical protocols may result in more sensitive screening and ultimately the possible replacement of the intestinal biopsy as the gold standard for celiac disease diagnosis.

  10. 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.

  11. Symptoms of Celiac Disease

    MedlinePlus

    ... before they can generate an autoimmune response to gluten and have their blood tested. 3.Any individual ... act in unpredictable ways. Some people can eat gluten for fifty years and then develop celiac disease, ...

  12. Celiac Disease Tests

    MedlinePlus

    ... the complications a person may experience, such as malnutrition , malabsorption , and the involvement of other organs. Tests ... someone has signs and symptoms suggesting celiac disease, malnutrition , and/or malabsorption . The symptoms are often nonspecific ...

  13. Pediatric Celiac Disease

    MedlinePlus

    ... Sprue Association/USA Gluten Intoloerance Group of North America NASPGHAN Foundation Supporters Educational support for the NASPGHAN ... NASPGHAN) Celiac Disease Eosinophilic Esophagitis Pediatric IBD Nutrition & Obesity Reflux & GERD Research & Grants Our Supporters Site Map © ...

  14. [Celiac disease and malocclusion].

    PubMed

    Bilello, Giuseppa; Ciulla, Claudia; Caradonna, Carola

    2010-04-01

    Celiac disease is an autoimmune disease, caused by a permanent intolerance to gluten, that occurs in genetically predisposed individuals. It causes enteropathy. In these individuals a prolonged exposure to gluten increases the risk of developing other pathologies, which may affect both developing dentition and oral mucosa. Clinical presentations are various and atypical. Celiac patients may have enamel hypoplasia, higher prevalence of dental caries, delayed eruption of teeth and lower jaw growth. These factors predispose to malocclusion. PMID:20540401

  15. [Update on celiac disease].

    PubMed

    Moscoso J, Felipe; Quera P, Rodrigo

    2016-02-01

    The prevalence of Celiac disease in the general population is approximately 1% and remains undiagnosed in a significant proportion of individuals. Its clinical presentation includes the classical malabsorption syndrome, unspecific and extra-intestinal manifestations, and silent celiac disease. The serologic diagnosis has an elevated sensitivity and specificity and, at least in adult population, it must be confirmed by biopsy in every case. Diagnosis in subjects already on gluten free diet includes HLA typing and gluten challenge with posterior serologic and histologic evaluation. The core of the treatment is the gluten free diet, which must be supervised by an expert nutritionist. Monitoring must be performed with serology beginning at 3-6 months, and with histology two years after the diagnosis, unless the clinical response is poor. Poor disease control is associated with complications such as lymphoma and small bowel adenocarcinoma. In the future, it is likely that new pharmacologic therapies will be available for the management of celiac disease. PMID:27092676

  16. 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. PMID:26186878

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Ophthalmologic manifestations of celiac disease

    PubMed Central

    Martins, Thiago Gonçalves dos Santos; Costa, Ana Luiza Fontes de Azevedo; Oyamada, Maria Kiyoko; Schor, Paulo; Sipahi, Aytan Miranda

    2016-01-01

    Celiac disease is an autoimmune disorder that affects the small intestine of genetically predisposed individuals. Ophthalmic manifestations are within the extra-intestinal manifestations, and can be divided into those of autoimmune disorders or those due to absorptive disabilities. This article reviewed the ophthalmologic manifestation of celiac disease. Ophthalmic symptoms are rare, but should be investigated in patients with celiac disease and taken into consideration as the first systemic manifestation. PMID:26949627

  2. Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients With Refractory Celiac Disease.

    PubMed

    Perfetti, Vittorio; Baldanti, Fausto; Lenti, Marco Vincenzo; Vanoli, Alessandro; Biagi, Federico; Gatti, Marta; Riboni, Roberta; Dallera, Elena; Paulli, Marco; Pedrazzoli, Paolo; Corazza, Gino Roberto

    2016-08-01

    Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein-Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of latency- and replication-associated proteins confirmed active infection. Further studies are needed to determine whether EBV infection contributes to the pathogenesis of refractory celiac disease and enteropathy-associated T-cell lymphoma.

  3. [Adult Celiac Disease].

    PubMed

    Many, Natalie; Biedermann, Luc

    2016-07-01

    Celiac disease is an immune-mediated enteropathy in genetically predisposed individuals, triggered by gluten ingestion. Clinical manifestations include intestinal and extraintestinal symptoms. Affected individuals may also be completely asymptomatic. Nevertheless, an early diagnosis is essential in order to prevent long-term complications. Diagnostic approach involves serologic testing for tissue transglutaminase antibodies followed by duodenal biopsy in case of seropositivity. Until now, the only available treatment consists of a strict glute-free diet. Newer therapeutic strategies are currently being evaluated in clinical trials. PMID:27381303

  4. [Adult Celiac Disease].

    PubMed

    Many, Natalie; Biedermann, Luc

    2016-07-01

    Celiac disease is an immune-mediated enteropathy in genetically predisposed individuals, triggered by gluten ingestion. Clinical manifestations include intestinal and extraintestinal symptoms. Affected individuals may also be completely asymptomatic. Nevertheless, an early diagnosis is essential in order to prevent long-term complications. Diagnostic approach involves serologic testing for tissue transglutaminase antibodies followed by duodenal biopsy in case of seropositivity. Until now, the only available treatment consists of a strict glute-free diet. Newer therapeutic strategies are currently being evaluated in clinical trials.

  5. Celiac disease: a review.

    PubMed

    Guandalini, Stefano; Assiri, Asaad

    2014-03-01

    Triggered by the ingestion of gluten in genetically predisposed individuals, celiac disease is the most common genetically based food intolerance in the world, with a prevalence among approximately 1% of the general population. This enteropathy may appear at any age and is characterized by a wide variety of clinical signs and symptoms that go well beyond the gastrointestinal tract. In young children, gastrointestinal presentations are common and include chronic diarrhea, failure to thrive, and abdominal distention; however, extraintestinal manifestations are becoming increasingly more common. They include numerous conditions such as dermatitis herpetiformis, anemia, dental enamel hypoplasia, recurrent oral aphthae, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminase levels, and female infertility. Therefore, diagnosing celiac disease requires a high degree of suspicion, followed by correct screening and a confirmatory test with an intestinal biopsy. After diagnosis, a strict gluten-free diet must be followed, which in most cases will bring a marked improvement of symptoms. However, there are important compliance and quality-of-life problems, especially in adolescents. PMID:24395055

  6. Celiac Disease Facts and Figures

    MedlinePlus

    ... When a person who has celiac disease consumes gluten, a protein found in wheat, rye and barley, ... than 40- folds. Source: Duration of exposure to gluten and risk for autoimmune disorders in patients with ...

  7. Family recognition of celiac disease

    PubMed Central

    Bąk-Romaniszyn, Leokadia

    2013-01-01

    Celiac disease is a permanent intolerance to gluten that leads to small-bowel mucosal villous atrophy during autoimmune processes in genetically predisposed individuals. At present the diagnosis of celiac disease is based on characteristic clinical symptoms, the results of serological investigations (tissue transglutaminase ten times the upper limit of normal, presence of antiendomysial antibodies – EMA) and positive results of genetic examinations. The aim of this study is to present a medical history of a family in which the mother and younger son were diagnosed with celiac disease (confirmed by genotype examination). Before the genetic examination, the father and the elder son were also suspected of suffering from this disease (they were on gluten-free diets). The authors emphasize the usefulness of HLA-DQ2/DQ8 determination in first-degree relatives of celiac patients. PMID:24868289

  8. Celiac disease - nutritional considerations

    MedlinePlus

    Gluten-free diet; Gluten sensitive enteropathy - diet; Celiac sprue - diet ... To follow a gluten-free diet means, you need to avoid all foods, drinks, and medicines made with gluten. This means not eating ...

  9. Celiac Disease: What You Need to Know

    MedlinePlus

    ... intestine. People with celiac disease can’t eat gluten, a protein found in wheat, rye, and barley ... lip balms. When people with celiac disease eat gluten—even a tiny amount—their body’s immune system ...

  10. Genetics Home Reference: celiac disease

    MedlinePlus

    ... It appears likely that other contributors, such as environmental factors and changes in other genes, also influence the development of ... ME. Celiac disease: a model disease for gene-environment interaction. Cell Mol Immunol. 2011 Mar;8(2):93-5. doi: ... 2015 Published : September 8, 2016 The resources on this site should not be ...

  11. Potential Celiac Patients: A Model of Celiac Disease Pathogenesis

    PubMed Central

    Sperandeo, Maria Pia; Tosco, Antonella; Izzo, Valentina; Tucci, Francesca; Troncone, Riccardo; Auricchio, Renata; Romanos, Jihane; Trynka, Gosia; Auricchio, Salvatore; Jabri, Bana; Greco, Luigi

    2011-01-01

    Background and Aim Potential celiacs have the ‘celiac type’ HLA, positive anti-transglutaminase antibodies but no damage at small intestinal mucosa. Only a minority of them develops mucosal lesion. More than 40 genes were associated to Celiac Disease (CD) but we still do not know how those pathways transform a genetically predisposed individual into an affected person. The aim of the study is to explore the genetic features of Potential CD individuals. Methods 127 ‘potential’ CD patients entered the study because of positive anti-tissue transglutaminase and no mucosal lesions; about 30% of those followed for four years become frankly celiac. They were genotyped for 13 polymorphisms of ‘candidate genes’ and compared to controls and celiacs. Moreover, 60 biopsy specimens were used for expression studies. Results Potential CD bear a lighter HLA-related risk, compared to celiac (χ2 = 48.42; p value = 1×10−8). They share most of the polymorphisms of the celiacs, but the frequency of c-REL* G allele was suggestive for a difference compared to celiac (χ2 = 5.42; p value = 0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642: χ2 = 7.17, p value = 0.01). The expression of IL-21 was completely suppressed in potentials compared to celiacs (p value = 0.02) and to controls (p value = 0.02), in contrast IL-2, KIAA1109 and c-REL expression were over-expressed. Conclusions Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to differentiate this condition. Potential CD is a precious biological model of the pathways leading to the small intestinal mucosal damage in genetically predisposed individuals. PMID:21760890

  12. 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

  13. 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.

  14. [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. PMID:27273303

  15. [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.

  16. New and Developing Therapies for Celiac Disease

    PubMed Central

    Lewis, Suzanne K.; Green, Peter H. R.

    2009-01-01

    The treatment for celiac disease, a removal of gluten in the diet, is safe and effective for the vast majority of patients. There is a large body of evidence that the diagnosis and treatment of those with celiac disease ensures considerable health benefits. Although a gluten-free diet is the principal treatment for celiac disease, it is relatively expensive, inconvenient and difficult to adhere to. For these reasons, there is interest in developing alternative therapies. Emerging research for the treatment of celiac disease has focused on three areas: to decrease gluten exposure, to modify intestinal permeability and to modulate immune activation. Therapies developed thus far consist of enzymes designed to digest gluten and the use of inhibitors of paracellular permeability to decrease the migration of gluten peptides into the lamina propria. Other potential therapeutic maneuvers include the binding of gluten by polymers, the use of tissue transglutaminase (TTG) inhibitors and DQ2 or DQ8 blockers, or modulation of cytokine production. While all represent new and exciting therapies, an ideal therapy should have virtually no side effects similar to a gluten-free diet. A pharmaceutical agent may be used on an intermittent basis, such as following occasional gluten exposure or on a chronic basis to mitigate the effects of potential inadvertent ingestion of gluten. PMID:21180558

  17. What is Celiac Disease? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Celiac Disease What is Celiac Disease? Past Issues / Spring 2015 Table of Contents Celiac ... people choose the right foods. How common is celiac disease? Celiac disease affects people in all parts of ...

  18. Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity

    PubMed Central

    Anjum, Naheed; Baker, Philip N; Robinson, Nicola J; Aplin, John D

    2009-01-01

    Background Celiac disease (CD) occurs in as many as 1 in 80 pregnant women and is associated with poor pregnancy outcome, but it is not known if this is an effect on maternal nutrient absorption or, alternatively, if the placenta is an autoimmune target. The major autoantigen, tissue transglutaminase (tTG), has previously been shown to be present in the maternal-facing syncytiotrophoblast plasma membrane of the placenta. Methods ELISA was used to demonstrate the presence of antibodies to tissue transglutaminase in a panel of CD sera. Immunohistochemistry was used to evaluate the binding of IgA autoantibodies from CD serum to term placenta. In addition, novel direct binding and activity assays were developed to mimic the in vivo exposure of the villous placenta to maternal autoantibody. Results and Discussion CD IgA autoantibodies located to the syncytial surface of the placenta significantly more than IgA antibodies in control sera (P < 0.0001). The distribution of antigen was similar to that observed using a monoclonal antibody to tissue transglutaminase. Staining was reduced by pre-absorption of CD serum with recombinant human tissue transglutaminase. In direct binding assays, autoimmune immunoglobulin A (IgA) from the maternal compartment became associated with antigen at the syncytial surface of the placenta, as a result of which transglutaminase activity at this site was inhibited. Conclusion These data indicate that direct immune effects in untreated CD women may compromise placental function. PMID:19228395

  19. 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

  20. 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

  1. Intestinal stem cells and celiac disease

    PubMed Central

    Piscaglia, Anna Chiara

    2014-01-01

    Stem cells (SCs) are the key to tissue genesis and regeneration. Given their central role in homeostasis, dysfunctions of the SC compartment play a pivotal role in the development of cancers, degenerative disorders, chronic inflammatory pathologies and organ failure. The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d. According to the so-called Unitarian hypothesis, this renewal is driven by a common intestinal stem cell (ISC) residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Celiac disease (CD) can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins (gluten) in genetically predisposed individuals. Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic, immunological and environmental factors in CD, with a particular emphasis on intestinal barrier and gut microbiota. Conversely, little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet. Nonetheless, bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease. This manuscript summarizes the “state of the art” regarding CD and ISCs, their niche and potential role in the development and treatment of the disease. PMID:24772248

  2. Coexistence of Celiac Disease and Down Syndrome.

    ERIC Educational Resources Information Center

    Simila, Seppo; Kokkonen, Jourma

    1990-01-01

    Three Finnish patients with Down syndrome and celiac disease are described. The incidence of celiac disease among patients with Down syndrome was calculated to be 20 times greater than in children without Down syndrome, indicating that it should be kept in mind when patients suffer from recurrent diarrhea and/or delayed puberty. (Author/JDD)

  3. Therapeutic approaches for celiac disease

    PubMed Central

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  4. RICE BREAD FOR PEOPLE WITH CELIAC DISEASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This technical bulletin was written to describe new process to make whole rice bread (WRB) for Celiacs, a disease caused by proteins found in wheat, barley and rye. The rice is free of these proteins and hence an ideal grain to develop foods for Celiacs. Absence of these proteins, however make it ...

  5. Esophageal manifestations of celiac disease.

    PubMed

    Lucendo, A J

    2011-09-01

    Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated.

  6. 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. PMID:10075317

  7. Celiac Disease: Four Inches and Seven Pounds...

    MedlinePlus

    ... fruit and pancakes—as long as they are gluten-free. "Stella has celiac disease," explains her mother, ... finally diagnosed Stella. She's been on a strict gluten-free diet ever since, like so many thousands ...

  8. Lymphadenopathy in celiac disease: computed tomographic observations

    SciTech Connect

    Jones, B.; Bayless, T.M.; Fishman, E.K.; Siegelman, S.S.

    1984-06-01

    Lymphadenopathy in patients with celiac disease is generally viewed with alarm due to the association between celiac disease and intestinal lymphoma. Four patients with celiac disease are described in whom significant mesenteric and paraaortic adenopathy was demonstrated by computed tomogrophy (CT). The subsequent clinical course of these patients revealed no evidence of lymphoma. In two patients with longstanding celiac disease and recent relapse, exploratory laparotomy revealed reactive hyperplasia in the enlarged glands; in one patient this was associated with intestinal ulceration, and in the other no underlying pathology was found. Follow-up CT scans in both these patients demonstrated regression of the findings with clinical improvement. In the other two patients, CT was performed as part of the initial evaluation.

  9. 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

  10. 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.

  11. Endocrine manifestations in celiac disease

    PubMed Central

    Freeman, Hugh James

    2016-01-01

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison’s disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet. PMID:27784959

  12. Prevalence of Eating Disorders in Adults with Celiac Disease

    PubMed Central

    Passananti, V.; Siniscalchi, M.; Zingone, F.; Bucci, C.; Tortora, R.; Iovino, P.; Ciacci, C.

    2013-01-01

    Background. Symptoms of celiac disease negatively impact social activities and emotional state. Aim was to investigate the prevalence of altered eating behaviour in celiac patients. Methods. Celiac patients and controls completed a dietary interview and the Binge Eating Staircases, Eating Disorder Inventory (EDI-2), Eating Attitudes Test, Zung Self-Rating Depression Scale, State Trait Anxiety Inventory Forma Y (STAI-Y1 and STAI-Y2), and Symptom Check List (SCL-90). Results. One hundred celiac adults and 100 controls were not statistically different for gender, age, and physical activity. STAI-Y1 and STAI-Y2, Somatization, Interpersonal, Sensitivity, and Anxiety scores of the SLC-90 were higher in CD patients than controls. EDI-2 was different in pulse thinness, social insecurity, perfectionism, inadequacy, ascetisms, and interpersonal diffidence between CD and HC women, whilst only in interceptive awareness between CD and HC men. A higher EAT-26 score was associated with the CD group dependently with gastrointestinal symptoms. The EAT26 demonstrated association between indices of diet-related disorders in both CD and the feminine gender after controlling for anxiety and depression. Conclusion. CD itself and not gastrointestinal related symptoms or psychological factors may contribute pathological eating behavior in celiac adults. Eating disorders appear to be more frequent in young celiac women than in CD men and in HC. PMID:24369457

  13. Genome search in celiac disease.

    PubMed Central

    Greco, L; Corazza, G; Babron, M C; Clot, F; Fulchignoni-Lataud, M C; Percopo, S; Zavattari, P; Bouguerra, F; Dib, C; Tosi, R; Troncone, R; Ventura, A; Mantavoni, W; Magazzù, G; Gatti, R; Lazzari, R; Giunta, A; Perri, F; Iacono, G; Cardi, E; de Virgiliis, S; Cataldo, F; De Angelis, G; Musumeci, S; Clerget-Darpoux, F

    1998-01-01

    Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening. PMID:9497251

  14. Adult Celiac Disease and Its Malignant Complications

    PubMed Central

    2009-01-01

    Adult celiac disease is a chronic intestinal disorder that has been estimated to affect up to 1-2% of the population in some nations. Awareness of the disease has increased, but still it remains markedly underdiagnosed. Celiac disease is a pathologically defined condition with several characteristic clinical scenarios that should lead the clinician to suspect its presence. Critical to diagnosis is a documented responsiveness to a gluten-free diet. After diagnosis and treatment, symptoms and biopsy-proven changes may recur and appear refractory to a gluten-free diet. Recurrent symptoms are most often due to poor diet compliance, a ubiquitous and unrecognized gluten source, an initially incorrect diagnosis, or an associated disease or complication of celiac disease. Some patients with persistent symptoms and biopsy-proven changes may not have celiac disease at all, instead suffering from a sprue-like intestinal disease, so-called unclassified sprue, which is a specific entity that does not appear to respond to a gluten-free diet. Some of these patients eventually prove to have an underlying malignant cause, particularly lymphoma. The risk of developing lymphoma and other malignancies is increased in celiac disease, especially if initially diagnosed in the elderly, or late in the clinical course of the disease. However, recent studies suggest that the risk of gastric and colon cancer is low. This has led to the hypothesis that untreated celiac disease may be protective, possibly due to impaired absorption and more rapid excretion of fat or fat-soluble agents, including hydrocarbons and other putative cocarcinogens, which are implicated in the pathogenesis of colorectal cancer. PMID:20431755

  15. Multiplex assays to diagnose celiac disease.

    PubMed

    Lochman, Ivo; Martis, Peter; Burlingame, Rufus W; Lochmanová, Alexandra

    2007-08-01

    Patients with celiac disease are sensitive to the gluten fractions of wheat. Symptoms include gastrointestinal problems and a failure to thrive in children, but may range from headaches to general malaise in adults. Thus, it is difficult to diagnose celiac disease by symptoms alone. The standard diagnostic criteria include the presence of the characteristic anti-gliadin or anti-tissue transglutaminase antibodies (anti-tTG) in serum, flattened mucosa on intestinal biopsy, and improved symptoms on a gluten-free diet. Because of the ease of use of the tTG enzyme-linked immunosorbent assay (ELISA) compared to endomysial by indirect immunofluorescence assay, there has been much more screening for celiac disease in recent years. This increased screening showed that celiac disease was more prevalent than previously believed. We compared a new multiplex assay that includes a novel form of deamidated gliadin and recombinant human tTG as the antigens to other assays using standard antigens. In addition, the new assay detects the presence of selective IgA deficiency, which shows a 10-fold increase in prevalence in patients with celiac disease compared to the general population. The combination of sensitivity and specificity of the new multiplex assay was equal or better than those for standard assays. Thus the performance, ease of use, and ability to measure three clinically important parameters in a single test make the new multiplex assay a viable alternative to standard assays in a clinical lab.

  16. Quantitative image analysis of celiac disease

    PubMed Central

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2015-01-01

    We outline the use of quantitative techniques that are currently used for analysis of celiac disease. Image processing techniques can be useful to statistically analyze the pixular data of endoscopic images that is acquired with standard or videocapsule endoscopy. It is shown how current techniques have evolved to become more useful for gastroenterologists who seek to understand celiac disease and to screen for it in suspected patients. New directions for focus in the development of methodology for diagnosis and treatment of this disease are suggested. It is evident that there are yet broad areas where there is potential to expand the use of quantitative techniques for improved analysis in suspected or known celiac disease patients. PMID:25759524

  17. Quantitative image analysis of celiac disease.

    PubMed

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2015-03-01

    We outline the use of quantitative techniques that are currently used for analysis of celiac disease. Image processing techniques can be useful to statistically analyze the pixular data of endoscopic images that is acquired with standard or videocapsule endoscopy. It is shown how current techniques have evolved to become more useful for gastroenterologists who seek to understand celiac disease and to screen for it in suspected patients. New directions for focus in the development of methodology for diagnosis and treatment of this disease are suggested. It is evident that there are yet broad areas where there is potential to expand the use of quantitative techniques for improved analysis in suspected or known celiac disease patients.

  18. 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…

  19. 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.

  20. Elderly Onset Celiac Disease: A Narrative Review

    PubMed Central

    Cappello, Maria; Morreale, Gaetano C.; Licata, Anna

    2016-01-01

    Celiac sprue is a chronic disease, which usually occurs in children and young adults. However, it can develop in any age group, and the prevalence is increasing even in the elderly population. The atypical patterns of clinical presentation in this age group sometimes can cause a delay in diagnosis. Given the lower sensitivity and specificity of serological tests in the aged population, clinical suspect often arises in the presence of complications (autoimmune disorders, fractures, and finally, malignancy) and must be supported by endoscopic and imaging tools. In this review, we highlight the incidence and prevalence of celiac disease in the elderly, the patterns of clinical presentation, diagnosis, and the most frequent complications, with the aim of increasing awareness and reducing the diagnostic delay of celiac disease even in the elderly population. PMID:27486350

  1. Elderly Onset Celiac Disease: A Narrative Review.

    PubMed

    Cappello, Maria; Morreale, Gaetano C; Licata, Anna

    2016-01-01

    Celiac sprue is a chronic disease, which usually occurs in children and young adults. However, it can develop in any age group, and the prevalence is increasing even in the elderly population. The atypical patterns of clinical presentation in this age group sometimes can cause a delay in diagnosis. Given the lower sensitivity and specificity of serological tests in the aged population, clinical suspect often arises in the presence of complications (autoimmune disorders, fractures, and finally, malignancy) and must be supported by endoscopic and imaging tools. In this review, we highlight the incidence and prevalence of celiac disease in the elderly, the patterns of clinical presentation, diagnosis, and the most frequent complications, with the aim of increasing awareness and reducing the diagnostic delay of celiac disease even in the elderly population. PMID:27486350

  2. Celiac Disease in Women with Hip Fractures

    PubMed Central

    LeBoff, Meryl S.; Cobb, Haley; Gao, Lisa Y.; Hawkes, William; Yu-Yahiro, Janet; Kolatkar, Nikheel S.; Magaziner, Jay

    2014-01-01

    Objective Celiac disease is associated with decreased bone density, however, the risk of fractures in celiac disease patients is unclear. We compared the prevalence of celiac disease between a group of women with hip fractures and a group of women undergoing elective joint replacement surgery and the association between celiac disease and vitamin D levels. Methods Two hundred eight community dwelling and postmenopausal women were recruited from Boston, MA (n=81) and Baltimore, MD (n=127). We measured tissue transglutaminase IgA by ELISA to diagnose celiac disease and 25-hydroxyvitamin D (25(OH)D) levels by radioimmunoassay in both women with hip fractures (n=157) and the control group (n=51), all of whom were from Boston. Subjects were excluded if they took any medications or had medical conditions that might affect bone. Results Median serum 25(OH)D levels were significantly lower (p< 0.0001) in the hip fracture cohorts compared to the elective joint replacement cohort (14.1 ng/ml vs. 21.3 ng/ml, respectively). There were no differences in the percentage of subjects with a positive tissue transglutaminase in the women with hip fractures versus the control group (1.91% vs. 1.61%, respectively). Conclusion Vitamin D levels are markedly reduced in women with hip fractures, however hip fracture patients did not show a higher percentage of positive tissue transglutaminase levels compared with controls. These data suggest that routine testing for celiac disease among hip fracture patients may not prove useful, although larger prospective studies among hip fracture subjects are needed. PMID:23732553

  3. Role of oats in celiac disease.

    PubMed

    Comino, Isabel; Moreno, María de Lourdes; Sousa, Carolina

    2015-11-01

    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.

  4. 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

  5. Celiac Disease and Overweight in Children: An Update

    PubMed Central

    Diamanti, Antonella; Capriati, Teresa; Basso, Maria Sole; Panetta, Fabio; Di Ciommo Laurora, Vincenzo Maria; Bellucci, Francesca; Cristofori, Fernanda; Francavilla, Ruggiero

    2014-01-01

    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. PMID:24451308

  6. Mucosal tissue transglutaminase expression in celiac disease

    PubMed Central

    Villanacci, Vincenzo; Not, Tarcisio; Sblattero, Daniele; Gaiotto, Tiziano; Chirdo, Fernando; Galletti, Anna; Bassotti, Gabrio

    2009-01-01

    Abstract Tissue transglutaminase (tTG) plays an important role in celiac disease pathogenesis and antibodies to tTG are a diagnostic marker of gluten-sensitive enteropathy. The aim of this study was to investigate the localization of tTG in the duodenal mucosa in control tissues and in different histological stages of celiac disease by using a commercial and a novel set of anti-tTG monoclonal antibodies, to see whether this assessment can be useful for diagnostic purpose. The distribution of tTG was firstly evaluated in 18 untreated celiac patients by using a commercial monoclonal antibody (CUB7402) against tissue transglutaminase enzyme and directed against the loop-core region of the enzyme. Thereafter, in further 30 untreated celiac patients we employed three newly characterized anti-tTG monoclonal antibodies produced against recombinant human-tTG. The epitopes recognized are located in three distinct domains of the protein corresponding to the core, C1 and C2 protein structure. Eleven age- and sex-matched patients with chronic duodenitis acted as controls. All subjects underwent upper endoscopy to obtain biopsy samples from the duodenum. Overall, we found that (i) tTG is equally expressed in CD at different stages of disease; (ii) tTG is expressed, at similar level, in CD and controls with duodenitis. Assessment of tTG level in biopsy samples by immunohistochemical methods is not useful in the clinical diagnostic work-up of CD. PMID:18373732

  7. Risk factors in familial forms of celiac disease.

    PubMed

    Freeman, Hugh James

    2010-04-21

    Celiac disease has been reported in up to 2% of some European populations. A similar risk has been identified in the America and Australia where immigration of Europeans has occurred. Moreover, an increasing number of celiac disease patients are being identified in many Asian countries, including China and India. Finally, celiac disease has also been detected in Asian immigrants and their descendants to other countries, such as Canada. Within these so-called "general" celiac populations, however, there are specific high risk groups that have an even higher prevalence of celiac disease. Indeed, the single most important risk factor for celiac disease is having a first-degree relative with already-defined celiac disease, particularly a sibling. A rate up to 20% or more has been noted. Risk is even greater if a specific family has 2 siblings affected, particularly if a male carries the human leukocyte antigen-DQ2. Both structural changes in the small bowel architecture occur along with functional changes in permeability, even in asymptomatic first-degree relatives. Even if celiac disease is not evident, the risk of other autoimmune disorders seems significantly increased in first-degree relatives as well as intestinal lymphoma. Identification of celiac disease is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated.

  8. 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

  9. Celiac disease in subjects with type 1 diabetes mellitus: a prevalence study in western Sicily (Italy).

    PubMed

    Greco, Domenico; Pisciotta, Maria; Gambina, Francesco; Maggio, Filippo

    2013-02-01

    The association between celiac disease and type 1 diabetes mellitus is well known. Up to now, celiac disease prevalence in children and adults with type 1 diabetes in Sicily has not been reported. The aim of this study was to assess the prevalence of celiac disease in patients with type 1 diabetes mellitus who come from a defined geographical area in western Sicily and to investigate the clinical features of these subjects. The records of 492 consecutive patients with type 1 diabetes mellitus referred in a period of 5 years were analyzed. During the period of the survey, out of 492 patients with type 1 diabetes, 22 (4.5 %) had a previous diagnosis of celiac disease. There were 14 females and 8 males; these patients showed a mean age of 13 years at diabetes onset. Diagnosis of celiac disease was often simultaneous or subsequent to that of diabetes. Autoimmune thyroiditis was coexisting in 8 patients (36 %). Our data confirm, in a Sicilian population, the not unusual association between celiac disease and type 1 diabetes, although prevalence rate is lower than in others Italian studies. Autoimmune thyroiditis is present with high prevalence in these patients. Celiac disease diagnosis often followed onset of type 1 diabetes, particularly in female subjects with a young age at diabetes onset; therefore, in these subjects, an active search for the presence of celiac disease is warranted for many years after appearance of diabetes.

  10. Celiac disease in subjects with type 1 diabetes mellitus: a prevalence study in western Sicily (Italy).

    PubMed

    Greco, Domenico; Pisciotta, Maria; Gambina, Francesco; Maggio, Filippo

    2013-02-01

    The association between celiac disease and type 1 diabetes mellitus is well known. Up to now, celiac disease prevalence in children and adults with type 1 diabetes in Sicily has not been reported. The aim of this study was to assess the prevalence of celiac disease in patients with type 1 diabetes mellitus who come from a defined geographical area in western Sicily and to investigate the clinical features of these subjects. The records of 492 consecutive patients with type 1 diabetes mellitus referred in a period of 5 years were analyzed. During the period of the survey, out of 492 patients with type 1 diabetes, 22 (4.5 %) had a previous diagnosis of celiac disease. There were 14 females and 8 males; these patients showed a mean age of 13 years at diabetes onset. Diagnosis of celiac disease was often simultaneous or subsequent to that of diabetes. Autoimmune thyroiditis was coexisting in 8 patients (36 %). Our data confirm, in a Sicilian population, the not unusual association between celiac disease and type 1 diabetes, although prevalence rate is lower than in others Italian studies. Autoimmune thyroiditis is present with high prevalence in these patients. Celiac disease diagnosis often followed onset of type 1 diabetes, particularly in female subjects with a young age at diabetes onset; therefore, in these subjects, an active search for the presence of celiac disease is warranted for many years after appearance of diabetes. PMID:22707396

  11. Celiac disease in children with atopic dermatitis.

    PubMed

    Ress, Krista; Annus, Triine; Putnik, Urve; Luts, Katrin; Uibo, Raivo; Uibo, Oivi

    2014-01-01

    Celiac disease (CD) is an autoimmune disorder of the small intestine with highly variable clinical presentation and frequently associated with various immune-mediated diseases. Among these immune-mediated diseases, atopy has been found frequently in individuals with CD. We aimed to study the prevalence of CD in Estonian children with atopic dermatitis (AD), a common multifactorial chronic inflammatory skin disease. We recruited 351 consecutive children with active AD (mean age 5.8 yrs, 57.6% boys) at Tallinn Children's Hospital, Estonia. Sera of all patients were tested for total serum immunoglobulin (Ig) A, for IgA- and IgG-type autoantibodies to tissue transglutaminase (IgA-anti-TG2, IgG-anti-TG2) and to deamidated gliadin peptides (IgA-anti-DGP, IgG-anti-DGP). The diagnosis of CD was confirmed histologically by small intestine biopsy according to the European Society of Paediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria. IgA deficiency was detected in nine patients with AD (2.6%), none of whom had IgG-anti-TG2 or IgG-anti-DGP seropositivity. IgA-anti-TG2 positivity was found in 4 (1.1%), IgG-anti-TG2 positivity in 2 (0.6%), IgA-anti-DGP positivity in 11 (3.1%), and IgG-anti-DGP in 10 (2.8%) patients. Celiac disease was confirmed in five (1.4%) patients with AD (95% confidence interval 0.46, 3.32) and all were histologically characterized as Marsh IIIa-IIIc stages and two presented with silent CD. In AD patients, CD prevalence was more than four times as high as in previously studied randomly selected schoolchildren in Estonia. Two patients with AD diagnosed with CD had no symptoms indicative of CD, in spite of extensive histologic changes in the small intestine mucosa. Therefore our study emphasizes the need for evaluating the cost-effectiveness of screening individuals with AD for CD in time to prevent long-term complications. PMID:24831884

  12. Selected luminal mucosal complications of adult celiac disease.

    PubMed

    Freeman, Hugh J

    2009-01-01

    Celiac disease is a gluten-dependent intestinal disorder that appears to be associated with several clinical conditions. Some involve the luminal mucosa of the stomach and intestinal tract and may, occasionally, complicate the course of celiac disease. Collagenous colitis has been associated with celiac disease and may lead to chronic diarrhea. Conversely, some of these clinical disorders that involve the luminal mucosa of the stomach and intestine may represent the initial clinical presentation of celiac disease. These disorders should be considered in patients with celiac disease who develop recurrent or refractory symptoms despite adherence to a strict gluten-free diet. Detection of collagenous disorders that affect the luminal mucosa of the stomach or intestinal tract may result in recognition of underlying celiac disease. PMID:21694821

  13. Foods for patients with celiac disease.

    PubMed Central

    Campbell, J. A.

    1982-01-01

    As a general rule patients with celiac disease must avoid five cereals--wheat rye, triticale, barley and oats. Very sensitive individuals must also avoid two products of these cereals--malt and hydrolyzed vegetable protein. Some less sensitive individuals may be able to tolerate barley and oats in small quantities. All other foods are acceptable, including the cereals corn, rice, buckwheat, millet and sorghum, as well as malt-flavored breakfast cereals. Wine, spirits, beer and ale are also acceptable unless otherwise contraindicated. Monosodium glutamate, other food additives and pharmaceutical preparations are also acceptable. The ingredients of prepackaged processed foods are listed on the labels. Patients with celiac disease must examine labels to ensure that they avoid the harmful cereals. With appropriate precautions they need not be concerned about eating away from home. PMID:7139445

  14. 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.

  15. Celiac Disease Presenting as Profound Diarrhea and Weight Loss - A Celiac Crisis.

    PubMed

    Bul, Vadim; Sleesman, Brett; Boulay, Brian

    2016-01-01

    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

  16. 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).

  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. 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.

  19. 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

  20. 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. PMID:26109797

  1. 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.

  2. [Frequency of celiac disease and irritable bowel syndrome coexistance and its influence on the disease course].

    PubMed

    Zwolińska-Wcisło, Małgorzata; Galicka-Latała, Danuta; Rozpondek, Piotr; Rudnicka-Sosin, Lucyna; Mach, Tomasz

    2009-01-01

    Celiac disease is increasingly recognized autoimmune enteropathy caused by a permanent gluten intolerance. Gluten is the main storage protein of wheat, in genetically predisposed individuals. Celiac disease risk in first degree relatives is about 10%. Diarrhea and changes of bowel movement, observed as well in celiac disease as in IBS, may lead to misdiagnosis of IBS basing on the Rome criteria or may be associated with coexistence of both diseases. The aim of the study was to assess the celiac disease prevalence in patients with irritable bowel syndrome. The study group comprised 200 patients (120 women and 80 men) aged 18-78 years (mean: 46.7 years) with diarrhoeal form of irritable bowel syndrome (IBS), according to the Rome criteria II. At the beginning and after a three month period anti tissue transglutaminase antibodies (IgA tTG) were estimated. Gastroscopy with biopsy where performed in those with IgA tTG titre above 1/200. 40 patients were immunologically positive and 14 of them have histopathologically proven celiac disease. In the group of patients with detected celiac disease, gluten free diet was applied besides the treatment with trimebutin or mebewerin, recommended for IBS. After 6 months the decrease of IgA tTG titre in the serum was observed. In 5 of these patients IgA tTG level was negative. It was associated with the significant decrease of clinical symptoms, such as diarrhea and flatulence. The remaining symptoms, such as abdominal pain, feeling of incomplete defecation demanded continuation of IBS treatment. With regard to often atypical celiac disease symptoms--adult active searching should be performed to differentiate from irritable bowel syndrome. PMID:19689036

  3. Is the Prevalence of Celiac Disease Higher than the General Population in Inflammatory Bowel Diseaese?

    PubMed Central

    Jandaghi, Elahe; Hojatnia, Mona; Vahedi, Homayoon; Shahbaz-Khani, Bijan; Kolahdoozan, Shadi; Ansari, Reza

    2015-01-01

    BACKGROUND In some studies inflammatory bowel disease (IBD) and celiac disease were considered to be associated and some belive that this association may influence the prognosis of IBD. However, there is a cosiderable controversy regarding this association. Therefore ,we aimed to assess the association of these two common digestive diseases and evaluate the complications of this association. METHODS In this comparative study, 200 patients with ulceritive colitis (UC) and 206 patients with Crohn’s disease (CD) were evaluated for celiac disease using relevant diagnostic tests and pathologic studies. Total IgA, IgA tissue transgulaminase antibody and specific IgA anti endomysial antibody were asseyed. In cases of IgA deficiency, total IgG and IgG tissue TG and IgG anti endomyseal Ab were measured. Patients with increased specific IgA and IgG antibodies for celiac disease, underwent endoscopy and 4 standard samples were obtained. Our results were compared with the results of the prevalence study of celiac disease in the general population. Data were analyzed using analytic and descriptive statistics at a significance level of 5%. RESULTS Among the studied patients, 1 patient with UC had elevated IgA anti tTG antibody and IgA anti-endomysial antibody who underwent endoscopy and celiac was confirmed on pathology. Hence, of the 200 patientswith UC, the diagnosis of celiac disease was confirmed in 1 patient (1:200) with no significant difference with the prevalence of celiac disease in the general population (1:166). However, none of our patients with Crohn’s disease had celiac disease (0:206). CONCLUSION We found no significant difference in the prevalence of celiac disease between patients with UC and the general population. Since most of our participants had a mild level of Crohn’s activation, none of those with Crohn’s disease had celiac disease. Complications of IBD including sclerosing cholangitis, may be more common in patients with concurrent celiac disease

  4. Is the Prevalence of Celiac Disease Higher than the General Population in Inflammatory Bowel Diseaese?

    PubMed

    Jandaghi, Elahe; Hojatnia, Mona; Vahedi, Homayoon; Shahbaz-Khani, Bijan; Kolahdoozan, Shadi; Ansari, Reza

    2015-04-01

    BACKGROUND In some studies inflammatory bowel disease (IBD) and celiac disease were considered to be associated and some belive that this association may influence the prognosis of IBD. However, there is a cosiderable controversy regarding this association. Therefore ,we aimed to assess the association of these two common digestive diseases and evaluate the complications of this association. METHODS In this comparative study, 200 patients with ulceritive colitis (UC) and 206 patients with Crohn's disease (CD) were evaluated for celiac disease using relevant diagnostic tests and pathologic studies. Total IgA, IgA tissue transgulaminase antibody and specific IgA anti endomysial antibody were asseyed. In cases of IgA deficiency, total IgG and IgG tissue TG and IgG anti endomyseal Ab were measured. Patients with increased specific IgA and IgG antibodies for celiac disease, underwent endoscopy and 4 standard samples were obtained. Our results were compared with the results of the prevalence study of celiac disease in the general population. Data were analyzed using analytic and descriptive statistics at a significance level of 5%. RESULTS Among the studied patients, 1 patient with UC had elevated IgA anti tTG antibody and IgA anti-endomysial antibody who underwent endoscopy and celiac was confirmed on pathology. Hence, of the 200 patientswith UC, the diagnosis of celiac disease was confirmed in 1 patient (1:200) with no significant difference with the prevalence of celiac disease in the general population (1:166). However, none of our patients with Crohn's disease had celiac disease (0:206). CONCLUSION We found no significant difference in the prevalence of celiac disease between patients with UC and the general population. Since most of our participants had a mild level of Crohn's activation, none of those with Crohn's disease had celiac disease. Complications of IBD including sclerosing cholangitis, may be more common in patients with concurrent celiac disease

  5. HLA genotyping in pediatric celiac disease patients

    PubMed Central

    Stanković, Biljana; Radlović, Nedeljko; Leković, Zoran; Ristić, Dragana; Radlović, Vladimir; Nikčević, Gordana; Kotur, Nikola; Vučićević, Ksenija; Kostić, Tatjana; Pavlović, Sonja; Zukić, Branka

    2014-01-01

    Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 90-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Children’s Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB1 alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1*02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development. PMID:25172978

  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. Celiac Disease and Thyroid Conditions

    MedlinePlus

    ... whole body to slow down. This is called hypothyroidism. If your thyroid begins to over-produce hormones ... and Grave’s Disease are two common causes of hypothyroidism and hyperthyroidism (respectively). Both are autoimmune diseases: autoimmune ...

  8. 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

  9. Association between celiac disease and primary lactase deficiency.

    PubMed

    Basso, M S; Luciano, R; Ferretti, F; Muraca, M; Panetta, F; Bracci, F; Ottino, S; Diamanti, A

    2012-12-01

    Primary lactase deficiency (PLD) is a common inherited condition caused by a reduced activity of lactase. Two single-nucleotide polymorphisms C/T(-13910) and G/A(-22018) upstream of the lactase gene are associated with lactase nonpersistence. In celiac disease (CD) patients, lactose intolerance could be due to secondary lactase deficiency and to PLD. The aim of this study were to evaluate the association of PLD and CD using genetic test, and to define the prevalence of PLD in celiac subjects compared with a control population. A total of 188 controls and 92 biopsy-proven CD patients were included in the study. More than 70% of all subjects were found homozygous for the polymorphisms. Differences in the prevalence of PLD were not found between CD patients and controls.In conclusions, the hereditary lactase deficiency is frequent in Italian CD children as in control population.

  10. 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

  11. 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

  12. New strategies for diagnosis and management of celiac disease.

    PubMed

    Westerberg, Dyanne P; Gill, James M; Dave, Bhavin; DiPrinzio, Marie J; Quisel, Anna; Foy, Andrew

    2006-03-01

    Celiac disease is a gastrointestinal disorder characterized by inflammation, leading to injury to the mucosal lining of the small intestine. The inflammation occurs when gliadin, a protein found in such gluten-containing foods as wheat, rye, and barley, is ingested by genetically susceptible individuals. The mucosal damage and subsequent malabsorption of nutrients leads to various complications. Researchers estimate that more than 2 million people in the United States have celiac disease-a prevalence that is greater than was previously believed. Approximately 60,000 Americans are diagnosed annually with celiac disease. Until recently, diagnosis has been complicated by the fact that the indicators of celiac disease are nonspecific. However, because of the development of new, easy-to-administer serology tests, diagnosis has become much less complicated. After conducting a review of the literature, the authors recommend a serologic testing sequence for diagnosis of celiac disease and urge that adults and children with an assortment of symptoms be tested for this disease. Common signs and symptoms of celiac disease include anemia, arthralgia, fatigue, infertility, neuropathy, and weight loss, in addition to such gastrointestinal symptomatology as abdominal pain, anorexia, bloating, constipation, and diarrhea. The only treatment for patients with celiac disease remains a gluten-free diet.

  13. Generating Transgenic Mouse Models for Studying Celiac Disease.

    PubMed

    Ju, Josephine M; Marietta, Eric V; Murray, Joseph A

    2015-01-01

    This chapter provides a brief overview of current animal models for studying celiac disease, with a focus on generating HLA transgenic mouse models. Human Leukocyte Antigen class II molecules have been a particular target for transgenic mice due to their tight association with celiac disease, and a number of murine models have been developed which had the endogenous MHC class II genes replaced with insertions of disease susceptible HLA class II alleles DQ2 or DQ8. Additionally, transgenic mice that overexpress interleukin-15 (IL-15), a key player in the inflammatory cascade that leads to celiac disease, have also been generated to model a state of chronic inflammation. To explore the contribution of specific bacteria in gluten-sensitive enteropathy, the nude mouse and rat models have been studied in germ-free facilities. These reductionist mouse models allow us to address single factors thought to have crucial roles in celiac disease. No single model has incorporated all of the multiple factors that make up celiac disease. Rather, these mouse models can allow the functional interrogation of specific components of the many stages of, and contributions to, the pathogenic mechanisms that will lead to gluten-dependent enteropathy. Overall, the tools for animal studies in celiac disease are many and varied, and provide ample space for further creativity as well as to characterize the complete and complex pathogenesis of celiac disease.

  14. Psychological Dimensions of Celiac Disease in India.

    PubMed

    Vohra, Pankaj

    2016-01-01

    An epidemic of celiac disease is being witnessed in India as well as several other parts of the world. Awareness is important for early diagnosis and treatment so as to avoid long-term morbidity as well as irreversible complications. However, the key for resolution of the disease is good compliance to a gluten-free diet. Unfortunately, the current scenario in India is that either gluten free foods are not easily available or are expensive and often not tested. This is especially true in schools and colleges and smaller towns. In addition, the stigma attached to gluten-free food makes it socially undesirable, and this is made worse by the lack of knowledge among peers, family members, advisors, and even health care providers. We need to make a strong pitch to overcome the confusion regarding the disease as well as the diet to avoid psychological and medical complications. PMID:27335528

  15. Psychological Dimensions of Celiac Disease in India

    PubMed Central

    Vohra, Pankaj

    2016-01-01

    An epidemic of celiac disease is being witnessed in India as well as several other parts of the world. Awareness is important for early diagnosis and treatment so as to avoid long-term morbidity as well as irreversible complications. However, the key for resolution of the disease is good compliance to a gluten-free diet. Unfortunately, the current scenario in India is that either gluten free foods are not easily available or are expensive and often not tested. This is especially true in schools and colleges and smaller towns. In addition, the stigma attached to gluten-free food makes it socially undesirable, and this is made worse by the lack of knowledge among peers, family members, advisors, and even health care providers. We need to make a strong pitch to overcome the confusion regarding the disease as well as the diet to avoid psychological and medical complications. PMID:27335528

  16. Extended HLA-D region haplotype associated with celiac disease

    SciTech Connect

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  17. 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

  18. 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

  19. Non responsive celiac disease due to coexisting hereditary fructose intolerance.

    PubMed

    Bharadia, Lalit; Shivpuri, Deepak

    2012-04-01

    Celiac disease is associated with several genetic disorders, but its association with hereditary fructose intolerance is rare. Hereditary fructose intolerance is a rare autosomal recessive disease of fructose metabolism presenting as vomiting after intake of fructose. An association between these two distinct genetic gastrointestinal disorders is important as treatment failure of celiac disease calls for careful evaluation for hereditary fructose intolerance. We report a patient with an association of these two disorders.

  20. [T lymphocyte populations of the intestinal mucosa in celiac disease in children. Immunohistochemical study].

    PubMed

    Olives, J P; Voigt, J J; al Saati, T; Nonnenmacher, L; Brousset, P; Delsol, G; Ghisolfi, J

    1990-01-01

    In order to study the distribution of lymphocyte subpopulations in a pathologic intestinal mucosa, the authors, instead of using the classic method by counting the number of lymphocytes, present an original method permitting the exploitation of quantified data from labelled surface cells by texture analyser coupled with a computerized system. We investigated 25 children presenting with chronic diarrhea and villous atrophy and 5 control subjects. Fifteen of the 25 children had celiac disease (10 active with total villous atrophy and 5, celiac disease in remission with healing mucosa), 5 cow's milk protein intolerance with total or partial villous atrophy and 5, chronic diarrhea with partial villous atrophy. Immunohistochemical study with monoclonal antibodies was carried out on frozen sections using a three-step immunoperoxidase technique. Compared with the 5 controls, patients with food intolerance (celiac disease and cow's milk protein intolerance) showed a significant increase of T suppressor lymphocytes (p less than 0.01 and p less than 0.05) in the epithelium, whereas there were more T helper lymphocytes in the lamina propria (p less than 0.05 and p less than 0.01). Non-treated celiac disease was distinguished from treated celiac disease by a marked increase in intra-epithelial T cytotoxic-suppressors. These results suggest that T cytotoxic-suppressors may be the mediators of the lesions observed in celiac disease. PMID:2179007

  1. 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

  2. Association between celiac disease and chronic hepatitis C.

    PubMed

    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

  3. Intestinal Microbiota and Probiotics in Celiac Disease

    PubMed Central

    Grzeskowiak, Lukasz Marcin; de Sales Teixeira, Tatiana Fiche; Gouveia Peluzio, Maria do Carmo

    2014-01-01

    SUMMARY Celiac disease (CD) is a common chronic autoimmune enteropathy caused by gluten intake. To date, the only therapy for CD is the complete exclusion of dietary sources of grains and any food containing gluten. It has been hypothesized that the intestinal microbiota is somehow involved in CD. For this reason, probiotics are appearing as an interesting adjuvant in the dietetic management of CD. This review aims to discuss the characteristics of the microbiota in CD subjects and the use of probiotics as a novel therapy for CD. Comparisons between children with CD and controls show that their microbiota profiles differ; the former have fewer lactobacilli and bifidobacteria. Specific probiotics have been found to digest or alter gluten polypeptides. It has also been demonstrated that some bacterial species belonging to the genera Lactobacillus and Bifidobacterium exert protective properties on epithelial cells from damage caused by gliadin. PMID:24982318

  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. 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

  6. Patients with Celiac Disease Are Not Followed Adequately

    PubMed Central

    Herman, Margot L.; Rubio-Tapia, Alberto; Lahr, Brian D.; Larson, Joseph J.; Van Dyke, Carol T.; Murray, Joseph A.

    2012-01-01

    Background & Aims Adherence to a gluten-free diet is the only effective treatment for celiac disease. It has been recommended that patients be followed, make regular visits to the clinic, and undergo serologic analysis for markers of celiac disease, although a follow-up procedure has not been standardized. We determined how many patients with celiac disease are actually followed. Methods We collected data on 122 patients with biopsy-proven celiac disease, diagnosed between 1996 and 2006 in Olmsted County, Minnesota (70% women, median age of 42 years) for whom complete medical records and verification of residency were available. We determined the frequency at which patients received follow-up examinations, from 6 months to 5 years after diagnosis. The Kaplan-Meier method was used to estimate event rates at 1 and 5 year(s). Patients were classified according to categories of follow-up procedures recommended by the American Gastroenterology Association (AGA). Results We estimated that by 1 and 5 year(s) after diagnosis with celiac disease, 41.0% and 88.7% of the patients had follow-up visits, 33.6% and 79.8% were assessed for compliance with a gluten-free diet, 3.3% and 15.8% met with a registered dietitian, 2.5% and 18.1% had an additional intestinal biopsy, and 22.1% and 65.6% received serologic testing for markers of celiac disease. Among 113 patients (93%) who were followed for more than 4 years, only 35% received follow-up analyses that were consistent with AGA recommendations. Conclusions Patients with celiac disease are not followed consistently. Follow-up examinations are often inadequate and do not follow AGA recommendations. Improving follow-up strategies for patients with celiac disease could improve management of this disease. PMID:22610009

  7. Dental and Oral Considerations in Pediatric Celiac Disease.

    PubMed

    Karlin, Sara; Karlin, Ellen; Meiller, Timothy; Bashirelahi, Nasir

    2016-01-01

    Celiac disease (CD) is the world's most common genetic food intolerance disorder. Children with celiac disease cannot tolerate gluten, a storage protein in wheat, rye, and barley. The first recognizable symptom in children is often an oral manifestation, rather than the typical gastrointestinal symptoms. The purpose of this paper is to review the oral and dental manifestations of CD to help pediatric dentists identify and refer atypically symptomatic patients to their pediatricians. PMID:27620516

  8. Shared Genetic Factors Involved in Celiac Disease, Type 2 Diabetes and Anorexia Nervosa Suggest Common Molecular Pathways for Chronic Diseases

    PubMed Central

    Mostowy, Joanna; Montén, Caroline; Gudjonsdottir, Audur H.; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel

    2016-01-01

    Background and Objectives Genome-wide association studies (GWAS) have identified several genetic regions involved in immune-regulatory mechanisms to be associated with celiac disease. Previous GWAS also revealed an over-representation of genes involved in type 2 diabetes and anorexia nervosa associated with celiac disease, suggesting involvement of common metabolic pathways for development of these chronic diseases. The aim of this study was to extend these previous analyses to study the gene expression in the gut from children with active celiac disease. Material and Methods Thirty six target genes involved in type 2 diabetes and four genes associated with anorexia nervosa were investigated for gene expression in small intestinal biopsies from 144 children with celiac disease at median (range) age of 7.4 years (1.6–17.8) and from 154 disease controls at a median (range) age 11.4.years (1.4–18.3). Results A total of eleven of genes were differently expressed in celiac patients compared with disease controls of which CD36, CD38, FOXP1, SELL, PPARA, PPARG, AGT previously associated with type 2 diabetes and AKAP6, NTNG1 with anorexia nervosa remained significant after correction for multiple testing. Conclusion Shared genetic factors involved in celiac disease, type 2 diabetes and anorexia nervosa suggest common underlying molecular pathways for these diseases. PMID:27483138

  9. High prevalence of celiac disease in Italian general population.

    PubMed

    Volta, U; Bellentani, S; Bianchi, F B; Brandi, G; De Franceschi, L; Miglioli, L; Granito, A; Balli, F; Tiribelli, C

    2001-07-01

    The worldwide increase of celiac disease prompted us to assess its prevalence in the Italian general population. The 3483 inhabitants of Campogalliano were tested for immunoglobulin A anti-endomysial antibodies. Twenty subjects showed antibody positivity and duodenal biopsy detected typical mucosal lesions of celiac disease in 17 of them; the remaining three cases had a normal villous architecture, but the finding of increased gamma/delta intraepithelial lymphocytes in all and the heterodimer DQA1*0501, DQB1*0201 in two of them was consistent with potential celiac disease. Only one patient had an overt malabsorption syndrome, characterized by diarrhea, weight loss, and severe weakness. In eight subjects atypical symptoms of celiac disease, such as dyspepsia and depression, were present, whereas the remaining subjects were silent. Celiac disease was more frequent in younger age groups. Our cross-sectional design study demonstrates that celiac disease prevalence in the Italian general population is 4.9 per 1000 (95% CI 2.8-7.8), increasing up to 5.7 per 1000 (95% CI 3.5-8.8) with the inclusion of potential cases. PMID:11478502

  10. Celiac Disease and Autoimmune-Associated Conditions

    PubMed Central

    Lauret, Eugenia; Rodrigo, Luis

    2013-01-01

    Celiac disease (CD) is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D); others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD) improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage. PMID:23984314

  11. Celiac disease: prevalence, diagnosis, pathogenesis and treatment.

    PubMed

    Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan B R

    2012-11-14

    Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

  12. Celiac disease in type 1 diabetes mellitus

    PubMed Central

    2012-01-01

    Celiac Disease (CD) occurs in patients with Type 1 Diabetes (T1D) ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD). In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD) on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients. PMID:22449104

  13. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

    PubMed Central

    Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

    2012-01-01

    Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either “typical” or “atypical”. In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

  14. Serologic celiac disease in patients with inflammatory bowel disease

    PubMed Central

    Tavakkoli, Hamid; Haghdani, Saeid; Adilipour, Haiedeh; Daghaghzadeh, Hamed; Minakari, Mohammad; Adibi, Peyman; Ahmadi, Khalil; Emami, Mohammah Hasan

    2012-01-01

    Background: There is an association of celiac disease (CD) with several gastrointestinal illnesses. We aimed to determine the prevalence of CD in patients with inflammatory bowel disease (IBD) to evaluate the value of the routine serological tests for CD in these patients. Materials and Methods: patients with IBD underwent screening test for CD. The screening test was based on IgA anti-tTG antibody evaluated by ELISA method and IgA EMA (endomysial antibody) measured by the indirect immunofluorescence method. Fisher exact and chi-square and t tests were used for data analysis. Results: the study was conducted on 100 patients, with a mean age of 34.74 ± 12.03 (SD) years. The mean simplified Crohn's disease activity index was 90 ± 17 (SE) and the mean colitis activity index was 3.46± 0.96 (SE). Seventeen patients (17%) had IgA anti-tTG antibody levels above the cutoff point (> 20). Thirty-two patients were positive for IgA EMA. IgA EMA was positive in nine IgA anti-tTG positive patients (three patients with Crohn's Disease and six ones with ulcerative colitis). Then, the prevalence of serologic CD was 9% that was higher than that of general population. A significant correlation was found between the results of IgA EMA and those of IgA anti-tTG (P=0.001) whereas Fisher exact test revealed significant difference between frequency distribution of positive and negative results of IgA EMA and IgA anti-tTG in patients with ulcerative colitis and Crohn's disease (P=0). Conclusion: the prevalence of serologic CD in general population in Iran has been reported to be 0.6–0.96%. Then, its prevalence in our sample size was about ten times more than that in general population. PMID:23264789

  15. Celiac Disease and Cystic Fibrosis: Challenges to Differential Diagnosis.

    PubMed

    Ramos, Alessandra Teixeira Pessoa; Figueirêdo, Manuella Machado; Aguiar, Ana Paula de B; Almeida, Carolina de Godoy; Mendes, Patrícia S A; Souza, Edna Lucia

    2016-01-01

    Cystic fibrosis and celiac disease were considered a single clinical entity for many years. Differentiation between the diseases occurred some time in the 1930s of the 20th Century. Both diseases may present the intestinal malabsorption syndrome and similar clinical manifestations that contribute to difficulties with clinical distinction. We describe a report of two patients with initial diagnosis of cystic fibrosis, who were subsequently diagnosed with celiac disease. These case reports emphasize the possibility of false positivity being shown in the sweat test in CD, which may result in delayed diagnosis and inadequate management of this disease. PMID:27552792

  16. HLA-G and susceptibility to develop celiac disease.

    PubMed

    Catamo, Eulalia; Zupin, Luisa; Segat, Ludovica; Celsi, Fulvio; Crovella, Sergio

    2015-01-01

    The Human Leukocyte Antigen-G has immunomodulatory function and its expression has been associated with several diseases. In our study we analyzed HLA-G polymorphisms in order to evaluate their possible association with susceptibility to celiac disease development. A total of 420 celiac patients and 509 controls were genotyped for HLA-G polymorphisms. We sequenced 800bp upstream the ATG codon (5' upstream regulatory region) and the whole 3' untranslated region of the HLA-G gene, whereas the ΔC deletion at exon 3 was detected by RFLP-PCR. Five polymorphisms (namely -477 C>G, -369 C>A, 14bp del/ins, 3187 A>G, 3196 C>G) and one haplotype (TCGGTACGAAITCCCGAG) were significantly more frequent in celiac patients than controls and associated with increased disease susceptibility. The 14bp I/I, 3187 G/G, 3196 G/G genotypes and TCGGTACGAAITCCCGAG haplotype, were still significantly associated with increased disease susceptibility (and in addition also the 3003 C/C genotype) when the analysis was restricted to patients and controls presenting the DQ2.5 or DQ8 HLA-DQ celiac disease risk haplotypes. Our findings indicate an association between HLA-G gene polymorphisms and susceptibility to celiac disease development, suggesting that HLA-G molecule is possibly involved in the pathogenesis of the disease.

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

    PubMed

    Mearin, Fermín; Montoro, Miguel

    2014-08-01

    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.

  18. Remission of severe aphthous stomatitis of celiac disease with etanercept

    PubMed Central

    2013-01-01

    Celiac disease is a common autoimmune disease triggered by gluten-containing foods (wheat, barley and rye) in genetically predisposed individuals. We present a patient with celiac disease complicated by severe aphthous stomatitis resulting in impairing swallowing, chewing and speaking. This led to weight loss, psychosocial problems as well as inability to perform her work. A variety of topical and systemic medications used resulted in either no improvement or only partial alleviation of the patient’s symptoms. After informed consent, etanercept was initiated and resulted in complete remission of aphthous stomatitis, decrease in arthralgia and fatigue and considerable improvement in her quality of life. The use of newer biological agents for selected and severe manifestations of celiac disease may lead to improved morbidity in these patients, but more studies are needed to determine long-term efficacy as well as safety of these drugs in the mucosal and/or systemic complications of this disease. PMID:24365222

  19. Microscopic Colitis (Lymphocytic and Collagenous), Eosinophilic Colitis, and Celiac Disease

    PubMed Central

    Villanueva, M. Sophia; Alimi, Yewande

    2015-01-01

    Multiple tests are needed to diagnose a patient with noninfectious diarrhea. Some patients will be mistakenly labeled as diarrhea-predominant irritable bowel syndrome (IBS-D) because of nonspecific computed tomographic scans and grossly normal endoscopic findings. It is crucial to understand other less common pathologies to avoid these instances of misdiagnosis. This article focuses on microscopic colitis (MC), eosinophilic colitis (EC), and celiac disease. MC is an inflammatory condition of the colon that presents with two subtypes, only to be differentiated by histology. EC is a rare chronic inflammatory process. Depending on the extent of the disease, it can present with mild diarrhea, malabsorption, or at its worst, cause obstruction and perforation. Celiac disease affects the small bowel, but interestingly can present similarly to colitis. Both MC and EC respond to oral budesonide. Patients with celiac disease improve on gluten-free diets. These treatments are distinctly different from typical IBS-D care plans. PMID:26034409

  20. Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome.

    PubMed

    Dickey, W; McConnell, B

    1999-02-01

    We describe two patients with Paterson-Brown Kelly (Plummer-Vinson) syndrome whose iron deficiency anemia was due to celiac disease. They presented with dysphagia 13 and 9 yr, respectively, before celiac disease was diagnosed. Neither had gastrointestinal symptoms suggestive of malabsorption. Celiac disease is a recognized cause of chronic iron deficiency and should be considered as an etiological factor for sideropenic dysphagia.

  1. Scale invariant texture descriptors for classifying celiac disease

    PubMed Central

    Hegenbart, Sebastian; Uhl, Andreas; Vécsei, Andreas; Wimmer, Georg

    2013-01-01

    Scale invariant texture recognition methods are applied for the computer assisted diagnosis of celiac disease. In particular, emphasis is given to techniques enhancing the scale invariance of multi-scale and multi-orientation wavelet transforms and methods based on fractal analysis. After fine-tuning to specific properties of our celiac disease imagery database, which consists of endoscopic images of the duodenum, some scale invariant (and often even viewpoint invariant) methods provide classification results improving the current state of the art. However, not each of the investigated scale invariant methods is applicable successfully to our dataset. Therefore, the scale invariance of the employed approaches is explicitly assessed and it is found that many of the analyzed methods are not as scale invariant as they theoretically should be. Results imply that scale invariance is not a key-feature required for successful classification of our celiac disease dataset. PMID:23481171

  2. Celiac disease and obstetric complications: a systematic review and metaanalysis.

    PubMed

    Saccone, Gabriele; Berghella, Vincenzo; Sarno, Laura; Maruotti, Giuseppe M; Cetin, Irene; Greco, Luigi; Khashan, Ali S; McCarthy, Fergus; Martinelli, Domenico; Fortunato, Francesca; Martinelli, Pasquale

    2016-02-01

    The aim of this metaanalysis was to evaluate the risk of the development of obstetric complications in women with celiac disease. We searched electronic databases from their inception until February 2015. We included all cohort studies that reported the incidence of obstetric complications in women with celiac disease compared with women without celiac disease (ie, control group). Studies without a control group and case-control studies were excluded. The primary outcome was defined a priori and was the incidence of a composite of obstetric complications that included intrauterine growth restriction, small for gestational age, low birthweight, preeclampsia and preterm birth. Secondary outcomes included the incidence of preterm birth, intrauterine growth restriction, stillbirth, preeclampsia, small for gestational age, and low birthweight. The review was registered with PROSPERO (CRD42015017263) before data extraction. All authors were contacted to obtain the original databases and perform individual participant data metaanalysis. Primary and secondary outcomes were assessed in the aggregate data analysis and in the individual participant data metaanalysis. We included 10 cohort studies (4,844,555 women) in this metaanalysis. Four authors provided the entire databases for the individual participant data analysis. Because none of the included studies stratified data for the primary outcome (ie, composite outcome), the assessment of this outcome for the aggregate analysis was not feasible. Aggregate data analysis showed that, compared with women in the control group, women with celiac disease (both treated and untreated) had a significantly higher risk of the development of preterm birth (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.66), intrauterine growth restriction (odds ratio, 2.48; 95% confidence interval, 1.32-4.67), stillbirth (odds ratio, 4.84; 95% confidence interval, 1.08-21.75), low birthweight (odds ratio, 1.63; 95% confidence interval, 1

  3. Intestinal permeability to (/sup 51/Cr)EDTA in children with Crohn's disease and celiac disease

    SciTech Connect

    Turck, D.; Ythier, H.; Maquet, E.; Deveaux, M.; Marchandise, X.; Farriaux, J.P.; Fontaine, G.

    1987-07-01

    (/sup 51/Cr)EDTA was used as a probe molecule to assess intestinal permeability in 7 healthy control adults, 11 control children, 17 children with Crohn's disease, and 6 children with untreated celiac disease. After subjects fasted overnight, 75 kBq/kg (= 2 microCi/kg) /sup 51/Cr-labeled EDTA was given by mouth; 24-h urinary excretion of (/sup 51/Cr)EDTA was measured and expressed as a percentage of the total oral dose. Mean and SD were as follows: control adults 1.47 +/- 0.62, control children 1.59 +/- 0.55, and patients with Crohn's disease or celiac disease 5.35 +/- 1.94. The difference between control children and patients was statistically significant (p less than 0.001). These results show that intestinal permeability to (/sup 51/Cr)EDTA is increased among children with active or inactive Crohn's disease affecting small bowel only or small bowel and colon, and with untreated celiac disease. The (/sup 51/Cr)EDTA permeability test could facilitate the decision to perform more extensive investigations in children suspected of small bowel disease who have atypical or poor clinical and biological symptomatology.

  4. Celiac disease in the Mediterranean area

    PubMed Central

    2014-01-01

    Background The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. Methods By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. Results The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. Conclusions This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines. PMID:24517104

  5. Isotretinoin Exposure and Risk of Celiac Disease

    PubMed Central

    Rashtak, Shadi; Khaleghi, Shahryar; Marietta, Eric V.; Pittelkow, Mark R.; Larson, Joseph J.; Lahr, Brian D.; Murray, Joseph A.

    2015-01-01

    Background Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins. Objective To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin. Material and Methods Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006–2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology. Results Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474). Conclusions There was no association between isotretinoin use and risk of either overt or latent CD. PMID:26287738

  6. Attitudes Toward Genetic Testing for Celiac Disease.

    PubMed

    Roy, Abhik; Pallai, Michele; Lebwohl, Benjamin; Taylor, Annette K; Green, Peter H

    2016-04-01

    HLA molecular typing for celiac disease (CD) is a genetic test with a high negative predictive value. The aim of this study is to explore knowledge of and attitudes towards genetic testing (GT). A 25-item questionnaire was developed by a multidisciplinary team and distributed to members of CD support groups across the United States. Respondents (n = 1835) were mainly female (88 %), married (76 %), and college-educated (55 %), with a median age range of 31-50 years. Those who were married (82 vs 75 %, p = 0.002), had children (82 vs 74 %, p < 0.001), and had pursued education beyond high school (81 vs 68 %, p = 0.004) were more likely to be aware of the availability of GT. On multivariable analysis, adjusting for age, sex, education, marital status, region of residence, and having children, college-education (OR 2.05, 95 % CI: 1.33-3.16) and having children (OR 1.56, 95 % CI: 1.15-2.11) remained significant predictors of GT awareness. A majority of patients with a personal or family history of CD planned GT for their children, and the most common concerns regarding GT were cost and impact on health care and/or insurance. In conclusion, awareness of GT is high among CD support group members. Efforts should be made to increase knowledge of GT in those with a lower educational level, and healthcare professionals should attempt to address concerns regarding GT cost and the impact of results on health care and insurance status.

  7. Celiac disease: is it really possible to overcome duodenal biopsy?

    PubMed

    Grande, Elisabetta; Ferranti, Silvia; Gaggiano, Carla; Di Virgilio, Nicola; Vascotto, Marina

    2016-05-06

    We report the case of a two-year-five-month-old child who underwent screening for celiac disease due to strong familiarity. During the first observation body weight and height were at 25th and 50th centile for gender and age. Physical examination did not reveal any sign of disease. Blood tests showed increased transaminases levels and antibodies research showed: tTG IgA: 100 UI/ml, tTG IgG: 36,6 UI/ml, EMA IgA: positive. HLA study revealed homozygous allelic combination DRB1*07;DQA102:01; DQB1* 02:02 with presence of a double copy of beta chain in the composition of the  DQ2 heterodymer. Biopsy with histological examination did find neither mucosal alteration  nor lymphocytic infiltrates (Marsh 0). During follow up with free diet the patient remained asymptomatic and all antibody titers decreased up to normalization. According to ESPGHAN guidelines the finding of hypertransaminasemia as sign of celiac hepatic inflammation, a more than 10-fold increase of tTG IgA and a high-risk HLA would permit diagnosis of celiac disease but histological examination done due to mismatch between paucity of clinical sings and a "multiple risk combination" excluded it, allowing diagnosis of potential celiac disease.  We believe that this case is interesting because of its being in contrast with current literature data that suggest a linear relationship between antibodies levels and histological damage with tTG IgA at the upper reference range in case of potential celiac disease. According to guidelines we could have avoided intestinal biopsy but we would have considered as celiac a patient who is maybe just potentially affected.

  8. Prevalence of Thyroid Autoimmunity in Children with Celiac Disease Compared to Healthy 12-Year Olds

    PubMed Central

    Ivarsson, Anneli; Högberg, Lotta; Svensson, Johan; Carlsson, Annelie

    2014-01-01

    Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screening-detected, were identified. Per case, 4 referents were matched. Blood samples were analyzed for autoantibodies against thyroid peroxidase (TPOAb). The cut-off value for TPO positivity was set to 100 U/mL. Results. Altogether, 335 celiac disease cases were found. In the entire celiac disease group, 7.2% (24/335) had elevated titers of TPOAb compared to 2.8% (48/1695) of the referents. Among the previously diagnosed celiac disease cases, 7.5% (7/93, OR 2.8, 95% CI 1.2–6.4) was TPOAb positive and among screening-detected cases, 7.0% (17/242, OR 2.6, 95% CI 1.5–4.6) was TPOAb positive. Conclusion. Children with celiac disease showed a higher prevalence of thyroid autoimmunity. We could not confirm the hypothesis that untreated celiac disease is associated with increased risk of developing thyroid autoimmunity. Early initiation of celiac disease treatment might not lower the risk for other autoimmune diseases. PMID:24592326

  9. The spectrum of celiac disease: epidemiology, clinical aspects and treatment.

    PubMed

    Tack, Greetje J; Verbeek, Wieke H M; Schreurs, Marco W J; Mulder, Chris J J

    2010-04-01

    Celiac disease is a gluten-sensitive enteropathy that affects people of all ages worldwide. This disease has emerged as a major health-care problem, as advances in diagnostic and screening methods have revealed its global prevalence. Environmental factors such as gluten introduction at childhood, infectious agents and socioeconomic features, as well as the presence of HLA-DQ2 and/or HLA-DQ8 haplotypes or genetic variations in several non-HLA genes contribute to the development of celiac disease. Growing insight into the variable clinical and histopathological presentation features of this disease has opened new perspectives for future research. A strict life-long gluten-free diet is the only safe and efficient available treatment, yet it results in a social burden. Alternative treatment modalities focus on modification of dietary components, enzymatic degradation of gluten, inhibition of intestinal permeability and modulation of the immune response. A small group of patients with celiac disease (2-5%), however, fail to improve clinically and histologically upon elimination of dietary gluten. This complication is referred to as refractory celiac disease, and imposes a serious risk of developing a virtually lethal enteropathy-associated T-cell lymphoma.

  10. 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

  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. Clinical Utility of Serologic Testing for Celiac Disease in Ontario

    PubMed Central

    2010-01-01

    Executive Summary Objective of Analysis The objective of this evidence-based evaluation is to assess the accuracy of serologic tests in the diagnosis of celiac disease in subjects with symptoms consistent with this disease. Furthermore the impact of these tests in the diagnostic pathway of the disease and decision making was also evaluated. Celiac Disease Celiac disease is an autoimmune disease that develops in genetically predisposed individuals. The immunological response is triggered by ingestion of gluten, a protein that is present in wheat, rye, and barley. The treatment consists of strict lifelong adherence to a gluten-free diet (GFD). Patients with celiac disease may present with a myriad of symptoms such as diarrhea, abdominal pain, weight loss, iron deficiency anemia, dermatitis herpetiformis, among others. Serologic Testing in the Diagnosis Celiac Disease There are a number of serologic tests used in the diagnosis of celiac disease. Anti-gliadin antibody (AGA) Anti-endomysial antibody (EMA) Anti-tissue transglutaminase antibody (tTG) Anti-deamidated gliadin peptides antibodies (DGP) Serologic tests are automated with the exception of the EMA test, which is more time-consuming and operator-dependent than the other tests. For each serologic test, both immunoglobulin A (IgA) or G (IgG) can be measured, however, IgA measurement is the standard antibody measured in celiac disease. Diagnosis of Celiac Disease According to celiac disease guidelines, the diagnosis of celiac disease is established by small bowel biopsy. Serologic tests are used to initially detect and to support the diagnosis of celiac disease. A small bowel biopsy is indicated in individuals with a positive serologic test. In some cases an endoscopy and small bowel biopsy may be required even with a negative serologic test. The diagnosis of celiac disease must be performed on a gluten-containing diet since the small intestine abnormalities and the serologic antibody levels may resolve or improve

  13. Prevalence of Celiac Disease in Turkish Children with Idiopathic Epilepsy

    PubMed Central

    Işikay, Sedat; Hizli, Şamil; Yilmaz, Kutluhan

    2014-01-01

    Objective: This study has examined the prevalence of celiac disease in Turkish children with idiopathic epilepsy. Methods: Children with idiopathic epilepsy were screened for celiac disease using the IgA anti-tissue transglutaminase antibody and compared with the healthy control group in order to find the association of celiac disease (CD) with idiopathic epilepsy. Upper gastrointestinal endoscopy and small intestinal biopsies were offered to all antibody-positive patients. Findings : A total of 214 children with the diagnosis of idiopathic epilepsy and 166 healthy children as control group were studied. Of the patients recruited, 55.1% had generalized epilepsy, and 44.9% had partial epilepsy. In 33 patients with partial epilepsy, electroclinical features were consistent with a diagnosis of childhood partial epilepsy with occipital paroxysms (CPEO). Two of 33 patients with CPEO had positive IgA anti-tissue transglutaminase antibodies in serology. Pathological examination of small intestinal biopsy specimens showed total villous atrophy in both of them. The prevalence of celiac disease among children with idiopathic epilepsy and CPEO was 0.9% and 6%, respectively. Conclusion: The results of the present study revealed that prevalence of CD is increased in children with epilepsy. On the other hand, as high as 6% prevalence of CD among patients with CPEO found in this study should be kept in mind and the clinicians should be aware of this association. PMID:25562021

  14. Epilepsy, occipital calcifications, and oligosymptomatic celiac disease in childhood.

    PubMed

    Arroyo, Hugo A; De Rosa, Susana; Ruggieri, Victor; de Dávila, María T G; Fejerman, Natalio

    2002-11-01

    The association of epilepsy, occipital calcifications, and celiac disease has been recognized as a distinct syndrome. The objective of this study was to present the clinical, electrophysiologic, and neuroradiologic features in a series of patients with this syndrome. Thirty-two patients with the constellation of epilepsy, occipital calcifications, and celiac disease were identified in our epilepsy clinic. The mean age was 11 years and the mean length of follow-up was 7.4 years. The 1990 criteria of the European Society of Pediatric Gastroenterology and Nutrition were used to diagnose celiac disease. The Kruskal-Wallis statistics test was employed with a signficance of P < .05. Thirty-one patients had partial seizures, 21 of them with symptoms related to the occipital lobe. In most patients, the epilepsy was controlled or the seizures were sporadic. Three developed severe epilepsy. Occipital calcifications were present in all cases. Computed tomography in 7 patients showed hypodense areas in the white matter around calcifications, which decreased or disappeared after a period of gluten-free diet in 3 patients. A favorable outcome of epilepsy was detected in patients with the earliest dietary therapy. This study presents the largest series of children with this syndrome outside Italy. White-matter hypodensities surrounding calcifications are rarely reported. A prompt diagnosis of celiac disease might improve the evolution of the epilepsy and may improve cognitive status. PMID:12585717

  15. Inflammatory bowel disease and celiac disease: Overlaps and differences

    PubMed Central

    Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción

    2014-01-01

    Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults. PMID:24803796

  16. Genetic variants associated with celiac disease and the risk for coronary artery disease.

    PubMed

    Jansen, Henning; Willenborg, Christina; Schlesinger, Sabrina; Ferrario, Paola G; König, Inke R; Erdmann, Jeanette; Samani, Nilesh J; Lieb, Wolfgang; Schunkert, Heribert

    2015-10-01

    Epidemiological evidence suggests that patients with celiac disease are at increased risk for coronary artery disease (CAD). Genetic-epidemiological analyses identified many single nucleotide polymorphisms (SNPs) associated with celiac disease. If there is a causal relation between celiac disease and CAD, one might expect that risk alleles primarily associated with celiac disease also increase the risk of CAD. In this study we identified from literature 41 SNPs that have been previously described to be genome-wide associated with celiac disease (p < 5 × 10(-08)). These SNPs were evaluated for their association with CAD in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) dataset, a meta-analysis comprising genome-wide SNP association data from 22,233 CAD cases and 64,762 controls. 24 out of 41 (58.5 %) risk alleles for celiac disease displayed a positive association with CAD (CAD-OR range 1.001-1.081). The remaining risk alleles for celiac disease (n = 16) revealed CAD-ORs of ≤1.0 (range 0.951-1.0). The proportion of CAD associated alleles was greater but did not differ significantly from the proportion of 50 % expected by chance (p = 0.069). One SNP (rs653178 at the SH2B3/ATXN2 locus) displayed study-wise statistically significant association with CAD with directionality consistent effects on celiac disease and CAD. However, the effect of this locus is most likely driven by pleiotropic effects on multiple other diseases. In conclusion, this genetically based approach provided no convincing evidence that SNPs associated with celiac disease contribute to the risk of CAD. Hence, common non-genetic factors may play a more important role explaining the coincidence of these two complex disease conditions.

  17. Magneto immunofluorescence assay for diagnosis of celiac disease.

    PubMed

    Kergaravat, Silvina V; Beltramino, Luis; Garnero, Nidia; Trotta, Liliana; Wagener, Marta; Fabiano, Silvia N; Pividori, Maria Isabel; Hernandez, Silvia R

    2013-10-10

    A magneto immunofluorescence assay for the detection of anti-transglutaminase antibodies (ATG2) in celiac disease was developed. The ATG2 were recognized by transglutaminase enzyme immobilized on the magnetic beads and then the immunological reaction was revealed by antibodies labeled with peroxidase. The fluorescent response of the enzymatic reaction with o-phenylenediamine and H2O2 as substrates was correlated with anti-transglutaminase titer, showing EC50 and LOD values of 1:11,600 and 1:74,500 of antibody titers, respectively. A total number of 29 sera samples from clinically confirmed cases of celiac disease and 19 negative control samples were tested by the novel magneto immunofluorescence assay. The data were submitted to the receiver-operating characteristic plot (ROC) analysis which indicated that 8.1 U was the most effective cut-off value to discriminate correctly between celiac and non-celiac patients. The immunofluorescence assay exhibited a sensitivity of 96.6%, a specificity of 89.5% and an efficiency 93.8% compared with the commercial optical ELISA kit. PMID:24070488

  18. Magneto immunofluorescence assay for diagnosis of celiac disease.

    PubMed

    Kergaravat, Silvina V; Beltramino, Luis; Garnero, Nidia; Trotta, Liliana; Wagener, Marta; Fabiano, Silvia N; Pividori, Maria Isabel; Hernandez, Silvia R

    2013-10-10

    A magneto immunofluorescence assay for the detection of anti-transglutaminase antibodies (ATG2) in celiac disease was developed. The ATG2 were recognized by transglutaminase enzyme immobilized on the magnetic beads and then the immunological reaction was revealed by antibodies labeled with peroxidase. The fluorescent response of the enzymatic reaction with o-phenylenediamine and H2O2 as substrates was correlated with anti-transglutaminase titer, showing EC50 and LOD values of 1:11,600 and 1:74,500 of antibody titers, respectively. A total number of 29 sera samples from clinically confirmed cases of celiac disease and 19 negative control samples were tested by the novel magneto immunofluorescence assay. The data were submitted to the receiver-operating characteristic plot (ROC) analysis which indicated that 8.1 U was the most effective cut-off value to discriminate correctly between celiac and non-celiac patients. The immunofluorescence assay exhibited a sensitivity of 96.6%, a specificity of 89.5% and an efficiency 93.8% compared with the commercial optical ELISA kit.

  19. Discerning the Role of Bacteroides fragilis in Celiac Disease Pathogenesis

    PubMed Central

    Sánchez, E.; Laparra, J. M.

    2012-01-01

    Celiac disease (CD) is associated with intestinal dysbiosis, which can theoretically lead to dysfunctions in host-microbe interactions and contribute to the disease. In the present study, possible differences in Bacteroides spp. and their pathogenic features between CD patients and controls were investigated. Bacteroides clones (n = 274) were isolated, identified, and screened for the presence of the virulence genes (bft and mpII) coding for metalloproteases. The proteolytic activity of selected Bacteroides fragilis strains was evaluated by zymography and, after gastrointestinal digestion of gliadin, by high-pressure liquid chromatography/electrospray ionization/tandem mass spectrometry. The effects of B. fragilis strains on Caco-2 cell culture permeability and inflammatory response to digested gliadin were determined. B. fragilis was more frequently identified in CD patients than in healthy controls, in contrast to Bacteroides ovatus. B. fragilis clones carrying virulence genes coding for metalloproteases were more abundant in CD patients than in controls. B. fragilis strains, representing the isolated clones and carrying metalloprotease genes, showed gelatinase activity and exerted the strongest adverse effects on the integrity of the Caco-2 cell monolayer. All B. fragilis strains also showed gliadin-hydrolyzing activity, and some of them generated immunogenic peptides that preserved or increased inflammatory cytokine production (tumor necrosis factor alpha) and showed increased ability to permeate through Caco-2 cell cultures. These findings suggest that increased abundance of B. fragilis strains with metalloprotease activities could play a role in CD pathogenesis, although further in vivo studies are required to support this hypothesis. PMID:22773639

  20. Local communication among mucosal immune cells in patients with celiac disease.

    PubMed

    van Bergen, Jeroen; Mulder, Chris J; Mearin, M Luisa; Koning, Frits

    2015-05-01

    In patients with celiac disease, gluten consumption causes inflammation of the duodenum, and, to a lesser extent, the proximal jejunum. Immune-dominant gluten peptides are modified by the enzyme TG2, leading to their high-affinity binding to HLA-DQ2 or HLA-DQ8 molecules, present in people with a predisposition to celiac disease. Gluten peptide-loaded HLA-DQ2 or HLA-DQ8 molecules are recognized by highly conserved receptors on CD4(+) T cells in the lamina propria. B cells specific for TG2 and modified gluten peptides are also abundant in the lamina propria of patients with celiac disease. In the epithelium, interleukin-15 activates intraepithelial lymphocytes that promote destruction of epithelial cells. However, it is not clear how the immune responses in the lamina propria and the epithelium, separated by a basement membrane, are linked. We review the immune processes that occur in the lamina propria and their potential effects on epithelial pathology in celiac disease.

  1. Duodenal-mucosal bacteria associated with celiac disease in children.

    PubMed

    Sánchez, Ester; Donat, Ester; Ribes-Koninckx, Carmen; Fernández-Murga, Maria Leonor; Sanz, Yolanda

    2013-09-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of cereal gluten proteins. This disorder is associated with imbalances in the gut microbiota composition that could be involved in the pathogenesis of CD. The aim of this study was to characterize the composition and diversity of the cultivable duodenal mucosa-associated bacteria of CD patients and control children. Duodenal biopsy specimens from patients with active disease on a gluten-containing diet (n = 32), patients with nonactive disease after adherence to a gluten-free diet (n = 17), and controls (n = 8) were homogenized and plated on plate count agar, Wilkins-Chalgren agar, brain heart agar, or yeast, Casitone, and fatty acid agar. The isolates were identified by partial 16S rRNA gene sequencing. Renyi diversity profiles showed the highest diversity values for active CD patients, followed by nonactive CD patients and control individuals. Members of the phylum Proteobacteria were more abundant in patients with active CD than in the other child groups, while those of the phylum Firmicutes were less abundant. Members of the families Enterobacteriaceae and Staphylococcaceae, particularly the species Klebsiella oxytoca, Staphylococcus epidermidis, and Staphylococcus pasteuri, were more abundant in patients with active disease than in controls. In contrast, members of the family Streptococcaceae were less abundant in patients with active CD than in controls. Furthermore, isolates of the Streptococcus anginosus and Streptococcus mutans groups were more abundant in controls than in both CD patient groups, regardless of inflammatory status. The findings indicated that the disease is associated with the overgrowth of possible pathobionts that exclude symbionts or commensals that are characteristic of the healthy small intestinal microbiota. PMID:23835180

  2. Diet and psoriasis, part II: celiac disease and role of a gluten-free diet.

    PubMed

    Bhatia, Bhavnit K; Millsop, Jillian W; Debbaneh, Maya; Koo, John; Linos, Eleni; Liao, Wilson

    2014-08-01

    Patients with psoriasis have been shown to have a higher prevalence of other autoimmune diseases including celiac disease, a condition marked by sensitivity to dietary gluten. A number of studies suggest that psoriasis and celiac disease share common genetic and inflammatory pathways. Here we review the epidemiologic association between psoriasis and celiac disease and perform a meta-analysis to determine whether patients with psoriasis more frequently harbor serologic markers of celiac disease. We also examine whether a gluten-free diet can improve psoriatic skin disease.

  3. 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.

  4. 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. PMID:25925923

  5. Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides.

    PubMed

    Hardy, Melinda Y; Tye-Din, Jason A; Stewart, Jessica A; Schmitz, Frederike; Dudek, Nadine L; Hanchapola, Iresha; Purcell, Anthony W; Anderson, Robert P

    2015-01-01

    Celiac disease (CD) is a common CD4(+) T cell mediated enteropathy driven by gluten in wheat, rye, and barley. Whilst clinical feeding studies generally support the safety of oats ingestion in CD, the avenin protein from oats can stimulate intestinal gluten-reactive T cells isolated from some CD patients in vitro. Our objective was to establish whether ingestion of oats or other grains toxic in CD stimulate an avenin-specific T cell response in vivo. We fed participants a meal of oats (100 g/day over 3 days) to measure the in vivo polyclonal avenin-specific T cell responses to peptides contained within comprehensive avenin peptide libraries in 73 HLA-DQ2.5(+) CD patients. Grain cross-reactivity was investigated using oral challenge with wheat, barley, and rye. Avenin-specific responses were observed in 6/73 HLA-DQ2.5(+) CD patients (8%), against four closely related peptides. Oral barley challenge efficiently induced cross-reactive avenin/hordein-specific T cells in most CD patients, whereas wheat or rye challenge did not. In vitro, immunogenic avenin peptides were susceptible to digestive endopeptidases and showed weak HLA-DQ2.5 binding stability. Our findings indicate that CD patients possess T cells capable of responding to immuno-dominant hordein epitopes and homologous avenin peptides ex vivo, but the frequency and consistency of these T cells in blood is substantially higher after oral challenge with barley compared to oats. The low rates of T cell activation after a substantial oats challenge (100 g/d) suggests that doses of oats commonly consumed are insufficient to cause clinical relapse, and supports the safety of oats demonstrated in long-term feeding studies.

  6. Altered Esophageal Mucosal Structure in Patients with Celiac Disease

    PubMed Central

    Pinto-Sánchez, María Inés; Nachman, Fabio D.; Fuxman, Claudia; Iantorno, Guido; Hwang, Hui Jer; Ditaranto, Andrés; Costa, Florencia; Longarini, Gabriela; Wang, Xuan Yu; Huang, Xianxi; Vázquez, Horacio; Moreno, María L.; Niveloni, Sonia; Bercik, Premysl; Smecuol, Edgardo; Mazure, Roberto; Bilder, Claudio; Mauriño, Eduardo C.; Verdu, Elena F.; Bai, Julio C.

    2016-01-01

    Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation. PMID:27446827

  7. Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

    PubMed

    Pinto-Sánchez, María Inés; Nachman, Fabio D; Fuxman, Claudia; Iantorno, Guido; Hwang, Hui Jer; Ditaranto, Andrés; Costa, Florencia; Longarini, Gabriela; Wang, Xuan Yu; Huang, Xianxi; Vázquez, Horacio; Moreno, María L; Niveloni, Sonia; Bercik, Premysl; Smecuol, Edgardo; Mazure, Roberto; Bilder, Claudio; Mauriño, Eduardo C; Verdu, Elena F; Bai, Julio C

    2016-01-01

    Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation. PMID:27446827

  8. 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. PMID:27216895

  9. 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.

  10. [Non-celiac disease non-wheat allergy wheat sensitivity].

    PubMed

    Zopf, Yurdagül; Dieterich, Walburga

    2015-11-01

    Non-celiac non-wheat allergy wheat sensitivity is regarded as discrete glutensensitivity diagnosed after the exclusion of celiac disease and wheat allergy. Due to the absence of reliable biomarkers no exact prevalence rates are known and estimations range between 0,5-6 %. Soon after ingestion of wheat, patients complain of intestinal symptoms mainly bloating, abdominal pain, diarrhea or nausea which improve fast under glutenfree diet. Often extraintestinal manifestation as tiredness, muscle or joint pain, headache and depression are reported. Actually, there are no serological markers and no intestinal mucosal damage was found in patients. The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers. In addition, the involvement of the intestinal microbiome in pathology of glutensensitivity must be considered.

  11. [Asymptomatic celiac disease in patient with chronic acalculous cholecystitis].

    PubMed

    Parfenov, A I; Dolgasheva, G M; Krums, L M; Bystrovskaia, E V; Sabel'nikova, E A; Gudkova, R B; Vorob'eva, N N; Lishchinskaia, A A

    2011-01-01

    We described a patient 40 years old, admitted to the clinic with periodic attacks of pain in the right upper quadrant. With ultrasound it was confirmed chronic acalculous cholecystitis, and at endoscopy and multiple biopsies revealed atrophy of the mucosa of the duodenum (DM), corresponding to celiac disease (stage III in the Marsh classification). Titer of antibodies to gliadin (AGA) and tissue transglutaminase (AtTG) were higher: 60 and 110 units/ml, respectively, at a rate of 10 units/ml. The patient was assigned a lifetime adherence to a gluten-free diet, serologic test and a control endoscopy with biopsy at 6 months. The important role of the doctor-endoscopist in the diagnosis of latent forms of celiac disease. The significance of DM atrophy in the pathogenesis of patients with chronic cholecystitis. PMID:21695960

  12. [Non-celiac disease non-wheat allergy wheat sensitivity].

    PubMed

    Zopf, Yurdagül; Dieterich, Walburga

    2015-11-01

    Non-celiac non-wheat allergy wheat sensitivity is regarded as discrete glutensensitivity diagnosed after the exclusion of celiac disease and wheat allergy. Due to the absence of reliable biomarkers no exact prevalence rates are known and estimations range between 0,5-6 %. Soon after ingestion of wheat, patients complain of intestinal symptoms mainly bloating, abdominal pain, diarrhea or nausea which improve fast under glutenfree diet. Often extraintestinal manifestation as tiredness, muscle or joint pain, headache and depression are reported. Actually, there are no serological markers and no intestinal mucosal damage was found in patients. The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers. In addition, the involvement of the intestinal microbiome in pathology of glutensensitivity must be considered. PMID:26536646

  13. Barriers impeding serologic screening for celiac disease in clinically high-prevalence populations

    PubMed Central

    2014-01-01

    Background Celiac disease is present in ~1% of the general population in the United States and Europe. Despite the availability of inexpensive serologic screening tests, ~85% of individuals with celiac disease remain undiagnosed and there is an average delay in diagnosis of symptomatic individuals with celiac disease that ranges from ~5.8-11 years. This delay is often attributed to the use of a case-based approach for detection rather than general population screening for celiac disease, and deficiencies at the level of health care professionals. This study aimed to assess if patient-centered barriers have a role in impeding serologic screening for celiac disease in individuals from populations that are clinically at an increased risk for celiac disease. Methods 119 adults meeting study inclusion criteria for being at a higher risk for celiac disease were recruited from the general population. Participants completed a survey/questionnaire at the William K. Warren Medical Research Center for Celiac Disease that addressed demographic information, celiac disease related symptoms (gastrointestinal and extraintestinal), family history, co-morbid diseases and conditions associated with celiac disease, and patient-centered barriers to screening for celiac disease. All participants underwent serologic screening for celiac disease using the IgA tissue transglutaminase antibody (IgA tTG) and, if positive, testing for IgA anti-endomysial antibody (IgA EMA) as a confirmatory test. Results Two barriers to serologic testing were significant across the participant pool. These were participants not knowing they were at risk for celiac disease before learning of the study, and participants not knowing where to get tested for celiac disease. Among participants with incomes less than $25,000/year and those less than the median age, not having a doctor to order the test was a significant barrier, and this strongly correlated with not having health insurance. Symptoms and co

  14. The Spectrum of Differences between Childhood and Adulthood Celiac Disease

    PubMed Central

    Ciccocioppo, Rachele; Kruzliak, Peter; Cangemi, Giuseppina C.; Pohanka, Miroslav; Betti, Elena; Lauret, Eugenia; Rodrigo, Luis

    2015-01-01

    An old saying states that ‘’children are not little adults” and this certainly holds true for celiac disease, as there are many peculiar aspects regarding its epidemiology, diagnosis, clinical presentations, associated diseases, and response to treatment in pediatric compared to adult populations, to such an extent that it merits a description of its own. In fact, contrary to the past when it was thought that celiac disease was a disorder predominantly affecting childhood and characterized by a malabsorption syndrome, nowadays it is well recognized that it affects also adult and elderly people with an impressive variability of clinical presentation. In general, the clinical guidelines for diagnosis recommend starting with specific serologic testing in all suspected subjects, including those suffering from extraintestinal related conditions, and performing upper endoscopy with appropriate biopsy sampling of duodenal mucosa in case of positivity. The latter may be omitted in young patients showing high titers of anti-transglutaminase antibodies. The subsequent management of a celiac patient differs substantially depending on the age at diagnosis and should be based on the important consideration that this is a lifelong condition. PMID:26506381

  15. Celiac disease with Evans syndrome and isolated immune thrombocytopenia in monozygotic twins: a rare association.

    PubMed

    Roganovic, Jelena

    2016-04-01

    Celiac disease is a multisystem immune-mediated disorder caused by exposure to dietary gluten in genetically predisposed individuals. The clinical presentation is characterized by a multitude and diversity of symptoms and complications. The coexistence of celiac disease with other autoimmune disorders has been established, most frequently with type 1 diabetes mellitus and autoimmune thyroiditis. The association of celiac disease with immune-mediated hematologic conditions has been rarely reported. This case study describes a pair of identical twin sisters with celiac disease associated with Evans syndrome in one sibling, and with isolated immune thrombocytopenia in the other. PMID:27312169

  16. Multiple common variants for celiac disease influencing immune gene expression

    PubMed Central

    Dubois, Patrick CA; Trynka, Gosia; Franke, Lude; Hunt, Karen A; Romanos, Jihane; Curtotti, Alessandra; Zhernakova, Alexandra; Heap, Graham AR; Ádány, Róza; Aromaa, Arpo; Bardella, Maria Teresa; van den Berg, Leonard H; Bockett, Nicholas A; de la Concha, Emilio G.; Dema, Bárbara; Fehrmann, Rudolf SN; Fernández-Arquero, Miguel; Fiatal, Szilvia; Grandone, Elvira; Green, Peter M; Groen, Harry JM; Gwilliam, Rhian; Houwen, Roderick HJ; Hunt, Sarah E; Kaukinen, Katri; Kelleher, Dermot; Korponay-Szabo, Ilma; Kurppa, Kalle; MacMathuna, Padraic; Mäki, Markku; Mazzilli, Maria Cristina; McCann, Owen T; Mearin, M Luisa; Mein, Charles A; Mirza, Muddassar M; Mistry, Vanisha; Mora, Barbara; Morley, Katherine I; Mulder, Chris J; Murray, Joseph A; Núñez, Concepción; Oosterom, Elvira; Ophoff, Roel A; Polanco, Isabel; Peltonen, Leena; Platteel, Mathieu; Rybak, Anna; Salomaa, Veikko; Schweizer, Joachim J; Sperandeo, Maria Pia; Tack, Greetje J; Turner, Graham; Veldink, Jan H; Verbeek, Wieke HM; Weersma, Rinse K; Wolters, Victorien M; Urcelay, Elena; Cukrowska, Bozena; Greco, Luigi; Neuhausen, Susan L.; McManus, Ross; Barisani, Donatella; Deloukas, Panos; Barrett, Jeffrey C; Saavalainen, Paivi; Wijmenga, Cisca; van Heel, David A

    2010-01-01

    We performed a second-generation genome wide association study of 4,533 celiac disease cases and 10,750 controls. We genotyped 113 selected SNPs with PGWAS<10−4, and 18 SNPs from 14 known loci, in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome wide significance (Pcombined<5×10−8), most contain immune function genes (BACH2, CCR4, CD80, CIITA/SOCS1/CLEC16A, ICOSLG, ZMIZ1) with ETS1, RUNX3, THEMIS and TNFRSF14 playing key roles in thymic T cell selection. A further 13 regions had suggestive association evidence. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P<0.0028, FDR 5%) with cis gene expression. PMID:20190752

  17. 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

  18. Advances in Diagnosis and Management of Celiac Disease

    PubMed Central

    Kelly, Ciarán P.; Bai, Julio C.; Liu, Edwin; Leffler, Daniel A.

    2015-01-01

    Celiac disease is an autoimmune disorder induced by dietary gluten in genetically predisposed individuals. It has a prevalence of ∼1% in many populations worldwide. New diagnoses have increased substantially, due to increased awareness, better diagnostic tools, and probable, real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA DQ2 and DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsies. However, according to recent controversial guidelines, a diagnosis can be made without biopsy in certain circumstances, especially for children. Symptoms, mortality, and risk for malignancy can each be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, as the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing non-dietary therapies. PMID:25662623

  19. 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. PMID:27547052

  20. Epidemiology of Celiac Disease in Iran: A Review

    PubMed Central

    Rostami Nejad, M; Rostami, K; Emami, MH; Zali, MR; Malekzadeh, R

    2011-01-01

    Celiac disease (CD) was traditionally believed to be a chronic enteropathy, almost exclusively affecting people of European origin. Celiac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. The availability of new, simple, very sensitive and specific serological tests has shown that CD is as common in Middle Eastern countries as in Europe, Australia and New Zealand where the major dietary staple is wheat. A high prevalence of CD has been found in Iran, in both the general population and the at-risk groups, i.e. patients with type 1 diabetes or irritable bowel syndrome (IBS). In developing countries, serological testing in at risk groups is necessary for early identification of celiac patients. Clinical studies show that presentation with non-specific symptoms or a lack of symptoms is as common in the Middle East as in Europe. Wheat is a major component of the Iranian diet and exposure to wheat proteins induces some degree of immune tolerance, leading to milder symptoms that may be mistaken with other GI disorders. The implementation of gluten free diet (GFD) is a major challenge for both patients and clinicians in Iran, especially since commercial gluten-free products are not available in this area. PMID:25197526

  1. Long-term fracture risk in patients with celiac disease: a population-based study in Olmsted County, Minnesota.

    PubMed

    Jafri, Mohammed R; Nordstrom, Charles W; Murray, Joseph A; Van Dyke, Carol T; Dierkhising, Ross A; Zinsmeister, Alan R; Melton, Lee J

    2008-04-01

    Celiac disease is associated with decreased bone density, but there are conflicting data regarding fracture risk. We determined the fracture incidence relative to matched controls in a population-based cohort with celiac disease before and after diagnosis. Olmsted County residents with celiac disease (n = 83) diagnosed between 1950 and 2002 were compared with 166 gender and age matched controls. Fracture histories were ascertained from each subject's medical records. Celiac disease is linked to an increased fracture risk before and after diagnosis. Before the index date, cases had a fracture rate twice that of controls (CI: 1.0-3.9, P = 0.045) and 2.5-fold greater after the index date (CI: 1.1-5.6, P = 0.026). Appendicular and axial fractures were 2.5 (CI: 0.9-6.5) and 3.2 times more likely (CI: 1.0-10.5) after the index date. These observations support a rationale for earlier detection of celiac disease, and active management of bone disease before bone effects have occurred, to reduce the persistent risk of fractures.

  2. Long-term fracture risk in patients with celiac disease: a population-based study in Olmsted County, Minnesota.

    PubMed

    Jafri, Mohammed R; Nordstrom, Charles W; Murray, Joseph A; Van Dyke, Carol T; Dierkhising, Ross A; Zinsmeister, Alan R; Melton, Lee J

    2008-04-01

    Celiac disease is associated with decreased bone density, but there are conflicting data regarding fracture risk. We determined the fracture incidence relative to matched controls in a population-based cohort with celiac disease before and after diagnosis. Olmsted County residents with celiac disease (n = 83) diagnosed between 1950 and 2002 were compared with 166 gender and age matched controls. Fracture histories were ascertained from each subject's medical records. Celiac disease is linked to an increased fracture risk before and after diagnosis. Before the index date, cases had a fracture rate twice that of controls (CI: 1.0-3.9, P = 0.045) and 2.5-fold greater after the index date (CI: 1.1-5.6, P = 0.026). Appendicular and axial fractures were 2.5 (CI: 0.9-6.5) and 3.2 times more likely (CI: 1.0-10.5) after the index date. These observations support a rationale for earlier detection of celiac disease, and active management of bone disease before bone effects have occurred, to reduce the persistent risk of fractures. PMID:17934823

  3. Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling.

    PubMed

    Lerner, Aaron; Matthias, Torsten

    2015-11-01

    Rheumatoid arthritis (RA) and celiac disease (CD) belong to the autoimmune disease family. Despite being separate entities they share multiple aspects. Epidemiologically they share comparable incidence environmental influences, associated antibodies and a recent incidental surge. They differ in their HLA pre-dispositions and specific predictive and diagnostic biomarkers. At the clinical level, celiac disease exhibits extra-intestinal rheumatic manifestations and RA gastrointestinal ones. Small bowel pathology exists in rheumatic patients. A trend towards responsiveness to a gluten free diet has been observed, ameliorating celiac rheumatic manifestations, whereas dietary interventions for rheumatoid arthritis remain controversial. Pathophysiologically, both diseases are mediated by endogenous enzymes in the target organs. The infectious, dysbiotic and increased intestinal permeability theories, as drivers of the autoimmune cascade, apply to both diseases. Contrary to their specific HLA pre-disposition, the diseases share multiple non-HLA loci. Those genes are crucial for activation and regulation of adaptive and innate immunity. Recently, light was shed on the interaction between host genetics and microbiota composition in relation to CD and RA susceptibility, connecting bugs and us and autoimmunity. A better understanding of the above mentioned similarities in the gut-joint inter-relationship, may elucidate additional facets in the mosaic of autoimmunity, relating CD to RA.

  4. 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.

  5. 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

  6. Celiac disease in a child with ulcerative colitis: a possible genetic association.

    PubMed

    Cheng, Sam X; Raizner, Aileen; Phatak, Uma P; Cho, Judy H; Pashankar, Dinesh S

    2013-02-01

    Celiac disease and inflammatory bowel disease including ulcerative colitis (UC) and Crohn's disease are both immune-mediated enteropathies. It is rare for both celiac disease and inflammatory bowel disease to occur together in an individual patient. This association has been reported in adults, however, very rarely in children. Here, we report an unusual case of an 8-year-old child with a history of anemia and failure to thrive who presented with bloody diarrhea. His evaluation showed anemia, elevated inflammatory markers, and positive celiac antibodies. Endoscopic evaluation revealed partial duodenal villous atrophy and pancolitis. He was diagnosed with celiac disease and UC and responded well to a gluten-free diet and steroid/mesalamine therapy. The patient's genetic testing revealed markers showing susceptibility for both celiac disease and UC. It is important to be aware of this association as both conditions can present with similar clinical features, however, require different therapeutic approaches.

  7. Salivary Ceruloplasmin Ferroxidase & Oxidase Activities in Celiac Patients

    PubMed Central

    Hasan, Hathama R.; Ghadhban, Jasim M.; Abudal Kadhum, Zahraa I.

    2012-01-01

    The aim of the current study was to evaluate salivary ferroxidase ceruloplasmin activities in celiac patients with different histopathological severity. This study included 75 celiac patients with different mean age (18.68 ± 11.13) year, who had positive screen for celiac antibodies, and who had gastrointestinal symptoms. In order to simplify the comparison with the healthy control group, celiac patients were divided into two groups according to their histopathological severity: severe (marsh IIIa, b, c) & less severe (marsh 0, I). All these patients have been evaluating for salivary ceruloplasmin (Cp) concentration and Cp ferroxidase activities. To confirm the presence of the enzymatic activity of this protein, polyacrylamide gel electrophoresis was carried out and then stained for Cp ferroxidase, as well as for Cp oxidase activity. Furthermore, the concentrations of salivary total protein, albumin, and globulin were measured in the studied groups. A significant increase (p<0.05) in salivary concentration of ceruloplasmin was found in all above mentioned patients groups in comparison to that of the control group, except for total villous atrophy (marsh IIIc) patients subgroup. Salivary Cp ferroxidase activity revealed statistically significant decrease among the patient groups as well as between them and the control group. The result of salivary total protein and globulin showed presence a significant increase (p<0.05) in comparison to that of the control group. Meanwhile albumin levels was found to increase non-significantly (p=0.186). PMID:23675269

  8. AMERICAN COLLEGE OF GASTROENTEROLOGY CLINICAL GUIDELINE: DIAGNOSIS AND MANAGEMENT OF CELIAC DISEASE

    PubMed Central

    Rubio-Tapia, Alberto; Hill, Ivor D; Kelly, Ciarán P; Calderwood, Audrey H; Murray, Joseph A

    2013-01-01

    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 clinical

  9. Celiac disease causing severe osteomalacia: an association still present in Morocco!

    PubMed

    Tahiri, Latifa; Azzouzi, Hamida; Squalli, Ghita; Abourazzak, Fatimazahra; Harzy, Taoufik

    2014-01-01

    Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.

  10. [The relationship between celiac disease (CD) and dental problems].

    PubMed

    Perez-Davidi, M

    2011-10-01

    With a prevalence of 1% in western populations, Celiac disease (CD) is one of the most common inflammatory disorders of the small intestine. CD is often assumed to have its onset in childhood, but it has recently been suggested that adults can also develop CD. Clinical manifestations vary according to age group: infants and young children present with diarrhea, abdominal distention, and failure to thrive, whereas adults that develop CD not only present with diarrhea, but also with silent manifestations such as anemia, osteoporosis, or neurological symptoms. 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. mmunohistochemistry of the small intestine of patients shows villous atrophy, crypt hyperplasia, and elevated levels of intraepithelial lymphocytes (IELs). The only therapy until now is a gluten-free diet, which will normalize the clinical and histological manifestations and allows the patients to live an otherwise normal life. part of the symptoms are oral manifestations as dental enamel defects, aphthous ulcers and Atrophic Glossitis. The prevalence of caries in CD patiens is law as compared to the healthy population and in some cases the normal eruption sequence of the teeth was damaged. Part of the undiagnosed CD patients are among our patients and the enamel defects they present are misdiagnosed as tetracycline pigmentation or white spot lesions it is the practitioners responsibility to add CD as a possible cause to the findings and refer the patient to further

  11. Seroprevalence of celiac disease among healthy adolescents in Saudi Arabia

    PubMed Central

    Aljebreen, Abdulrahman M; Almadi, Majid A; Alhammad, Alwaleed; Al Faleh, Faleh Z

    2013-01-01

    AIM: To identify the seroprevalence of celiac disease among healthy Saudi adolescents. METHODS: Between December 2007 and January 2008, healthy students from the 10th to 12th grades were randomly selected from three regions in Saudi Arabia. These regions included the following: (1) Aseer region, with a student population of 25512; (2) Madinah, with a student population of 23852; and (3) Al-Qaseem, with a student population of 16067. Demographic data were recorded, and a venous blood sample (5-10 mL) was taken from each student. The blood samples were tested for immunoglobulin A and immunoglobulin G endomysial antibodies (EMA) by indirect immunofluorescence. RESULTS: In total, 1167 students (614 males and 553 females) from these three regions were randomly selected. The majority of the study population was classified as lower middle class (82.7%). There were 26 (2.2%) students who had a positive anti-EMA test, including 17 females (3.1%) and 9 males (1.5%). Al-Qaseem region had the highest celiac disease prevalence among the three studied regions in Saudi Arabia (3.1%). The prevalence by region was as follows: Aseer 2.1% (10/479), Madinah 1.8% (8/436), and Al-Qaseem 3.2% (8/252). The prevalence in Madinah was significantly lower than the prevalence in Aseer and Al-Qaseem (P = 0.02). CONCLUSION: Our data suggest celiac disease prevalence might be one of the highest in the world. Further studies are needed to determine the real prevalence. PMID:23613632

  12. The intestinal B-cell response in celiac disease

    PubMed Central

    Mesin, Luka; Sollid, Ludvig M.; Niro, Roberto Di

    2012-01-01

    The function of intestinal immunity is to provide protection toward pathogens while preserving the composition of the microflora and tolerance to orally fed nutrients. This is achieved via a number of tightly regulated mechanisms including production of IgA antibodies by intestinal plasma cells. Celiac disease is a common gut disorder caused by a dysfunctional immune regulation as signified, among other features, by a massive intestinal IgA autoantibody response. Here we review the current knowledge of this B-cell response and how it is induced, and we discuss key questions to be addressed in future research. PMID:23060888

  13. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  14. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  15. Clinical Utility of Serologic Testing for Celiac Disease in Asymptomatic Patients

    PubMed Central

    2011-01-01

    Executive Summary Objective The objective of this evidence-based analysis was to evaluate the clinical utility of serologic testing for celiac disease in asymptomatic individuals presenting with one of the non-gastrointestinal conditions evaluated in this report. The clinical utility was based on the effects of a gluten-free diet (GFD) on outcomes specific to each of these conditions. The prevalence of celiac disease in asymptomatic individuals and one of these non-gastrointestinal conditions was also evaluated. Clinical Need and Target Population Celiac Disease Celiac disease is an autoimmune disease characterized by a chronic inflammatory state of the proximal small bowel mucosa accompanied by structural and functional changes. Technology Under Evaluation Serologic Tests for Celiac Disease There are a number of serologic tests for celiac disease available. Serologic tests are automated with the exception of the anti-endomysial antibody test, which is more time-consuming and operator-dependent than the other tests. Research Questions What is the prevalence of asymptomatic celiac disease in patients presenting with one of the non-gastrointestinal conditions evaluated? What is the effect of the gluten-free diet on condition-specific outcomes in patients with asymptomatic celiac disease presenting with one of the non-gastrointestinal conditions evaluated? What is the clinical utility of serologic testing for celiac disease in asymptomatic patients presenting with one of the non-gastrointestinal conditions evaluated? The clinical utility was defined as the impact of the GFD on disease specific outcomes. What is the risk of all-cause mortality and lymphoma in individuals with asymptomatic celiac disease? What is the budget impact of serologic testing for celiac disease in asymptomatic subjects presenting with one of the non-gastrointestinal conditions evaluated? Research Methods Study Population The study population consisted of individuals with newly diagnosed celiac

  16. 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. PMID:27443108

  17. Subclinical Celiac Disease and Crystal-Induced Kidney Disease Following Kidney Transplant

    PubMed Central

    Capolongo, Giovanna; Abul-Ezz, Sameh; Moe, Orson W.; Sakhaee, Khashayar

    2015-01-01

    Decreased kidney function from kidney deposition of calcium oxalate has been previously described in inflammatory bowel disease as well as following jejuno-ileal and Roux-en-Y gastric bypass surgeries. Although celiac disease is the most prevalent bowel abnormality associated with intestinal malabsorption, its relationship to high kidney oxalate burden and decreased kidney function has not been established. We report a case of subclinical celiac disease and hyperoxaluria that presented with loss of kidney function as a result of high oxalate load in the absence of overt diarrhea, documented intestinal fat malabsorption, and nephrolithiasis. Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients. We propose that this entity should be suspected in patients with chronic kidney disease in which the etiology of kidney damage has not been clearly established. PMID:22739230

  18. [Celiac disease associated with cutaneous sarcoidosic granuloma].

    PubMed

    Loche, F; Bazex, J

    1997-01-01

    Coeliac disease can be associated with numerous internal, skin and mucosa involvements: their physiopathology is often obscure. We report the case of a 14-year old female patient who suffered from a coeliac disease diagnosed in 1988 with considerable improvement with a gluten-free diet. Her two daughters also presented coeliac disease and her sister suffered from nevoid basal cell carcinoma syndrome. Four years later, she presented non pruriginous small nodules over both lower extremities. Skin biopsy revealed a non-caseating granuloma into the derm: we only could evocate sarcoidosis affecting the skin. The dermatological lesions improved during the following weeks with a gluten free diet and relapsed each time this diet was stopped. Many clinical associations with coeliac disease have been described with numerous visceral and skin-mucosa involvements. Eight cases of coeliac disease associated with sarcoidosis affecting the lung have been reported: in five cases, coeliac disease preceded sarcoidosis and in one case sarcoidosis relapsed each time gluten was reintroduced like in our case. This two diseases seem to share immunological and genetic disturbances.

  19. Is Dietitian Use Associated with Celiac Disease Outcomes?

    PubMed Central

    Mahadev, SriHari; Simpson, Suzanne; Lebwohl, Benjamin; Lewis, Suzanne K.; Tennyson, Christina A.; Green, Peter H. R.

    2013-01-01

    A gluten-free diet (GFD) is the treatment for celiac disease (CD), but due to its complexity, dietitian referral is uniformly recommended. We surveyed patients with CD to determine if dietitian use is associated with quality of life, symptom severity, or GFD adherence. The survey utilized three validated CD-specific instruments: the CD quality of life (CD-QOL), CD symptom index (CSI) and CD adherence test (CDAT). Four hundred and thirteen patients with biopsy-proven CD were eligible for inclusion. The majority (77%) were female and mean BMI was 24.1. Over three-quarters of patients (326, 79%) had seen a dietitian, however, 161 (39%) had seen a dietitian only once. Age, sex, and education level were not associated with dietitian use; nor was BMI (24.6 vs. 24.0, p = 0.45). On multivariate analysis, adjusting for age gender, education, duration of disease, and body mass index, dietitian use was not associated with CD-QOL, CSI, or CDAT scores. Our survey did not show an association between dietitian use and symptom severity, adherence, or quality of life. Delay in diagnosis was associated with poorer outcomes. This is a preliminary study with several limitations, and further prospective analysis is needed to evaluate the benefits and cost-effectiveness of dietitian-referral in the care of celiac disease patients. PMID:23676548

  20. Burden of celiac disease in the Mediterranean area

    PubMed Central

    Greco, Luigi; Timpone, Laura; Abkari, Abdelhak; Abu-Zekry, Mona; Attard, Thomas; Bouguerrà, Faouzi; Cullufi, Paskal; Kansu, Aydan; Micetic-Turk, Dusanka; Mišak, Zrinjka; Roma, Eleftheria; Shamir, Raanan; Terzic, Selma

    2011-01-01

    AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available confidence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic profiles amongst Mediterranean countries. RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550 000 symptomatic adults and about 240 000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600 000

  1. The role of infectious mediators and gut microbiome in the pathogenesis of celiac disease.

    PubMed

    Rostami Nejad, Mohammad; Ishaq, Sauid; Al Dulaimi, David; Zali, Mohammad Reza; Rostami, Kamran

    2015-04-01

    Celiac disease (CD) is an immune disorder that is associated with gluten sensitivity in people who are genetically predisposed. In celiac disease, food containing gluten mounts inflammatory response that results in villous atrophy in small bowel and increased permeability. This disorder is not only related to complications in the small bowel, but also has association with manifestations outside the GI tract. Small bowel mucosal immunity, exposed to infectious agents, is affected by CD; therefore, it is likely that patients with untreated celiac disease are more susceptible to infectious diseases. It is possible that sensitivity to gluten increases in patients infected with infectious diseases, and consequently infection may trigger CD in susceptible individuals. It is likely that, due to reduced immunity following the loss of intestinal villi, viral, bacterial, and parasitic infections develop faster in celiac disease patients and systemic complication occur more frequently. In addition, increased permeability, changing the microbiota following the chronic inflammation of the small intestine and abnormal immunological reactions are associated with celiac disease. PubMed, Medline, Google scholar, SID, and Magiran were searched for full text articles published between 1999 and 2014 in Persian and English. The associated keywords were used, and papers, which described particularly the impact of infectious agents on celiac disease, were selected. In this review, we have focused on the role of infectious agents and gut microbiota in the pathogenesis of celiac disease.

  2. Life Events and the Onset of Celiac Disease from a Patient’s Perspective

    PubMed Central

    Ciacci, Carolina; Siniscalchi, Monica; Bucci, Cristina; Zingone, Fabiana; Morra, Ivonne; Iovino, Paola

    2013-01-01

    Stressful events have been investigated in various immune-mediated diseases but not in celiac disease. Our aim was to examine the relationship of stressful events assessed by the standardized interview of Paykel with the diagnosis of celiac disease in comparison to patients, with a diagnosis of gastroesophageal reflux disease used as the control group. Adults with celiac disease (n = 186) reported more frequent and more severe life events in the years prior to the diagnosis than control patients (n = 96) (67.2% vs. 37.5%, p < 0.001, mean Paykel score 11.5 vs. 13.4, p = 0.001, respectively). Findings were not significantly different between celiac disease and control patients for the time lapse between the event and the diagnosis (mean 5.5 vs. 5.7 months). Pregnancy was defined as a negative event by 20.3% of celiac women, but never by control women. Findings were confirmed when analyses were repeated in the subgroup of patients of both groups with diagnosis made within one year of onset of symptoms. Data indicate that, before diagnosis, the number of stressful events in celiac disease was more frequent although less severe than in the control group suggesting that life events may favor the clinical appearance of celiac disease or accelerate its diagnosis. PMID:23989754

  3. Increased Prevalence of Celiac Disease in Patients with Unexplained Infertility in the United States: A Prospective Study

    PubMed Central

    Lebwohl, Benjamin; Wang, Jeffrey; Lee, Susie K.; Murray, Joseph A.; Sauer, Mark V.; Green, Peter H. R.

    2011-01-01

    Celiac disease is an autoimmune disorder which can present with a variety of non-gastrointestinal manifestations. In women, it may manifest with an assortment of gynecologic or obstetric disorders. Some reports have linked female infertility with undiagnosed celiac disease. Though there are a number of studies from Europe and the Middle East, only two prior American studies have examined the prevalence of “silent” celiac disease in a female infertility population. We prospectively performed serologic screening for celiac disease in 188 infertile women (ages 25–39). While we did not demonstrate an increased prevalence of celiac disease in our overall infertile female population, we were able to detect a significantly increased prevalence (5.9%) of undiagnosed celiac disease among women presenting with unexplained infertility (n=51). Our findings suggest the importance of screening infertile female patients, particularly those with unexplained infertility, for celiac disease. PMID:21682114

  4. [Compression stenosis of the celiac trunk as 1 of the causes of ischemic disease of the digestive organs].

    PubMed

    Potashov, L V; Ignashov, A M; Morozov, V P; Sedov, V M

    1980-02-01

    Experience in the treatment of 218 patients with compression stenosis of the celiac trunk is generalized. The clinical symptoms and the angiographic semiotics of the disease are described in detail. Active surgical tactics is substantiated and the results of operations are studied.

  5. Screening for Celiac Disease in a North American Population: Sequential Serology and Gastrointestinal Symptoms

    PubMed Central

    Katz, Kent D.; Rashtak, Shahrooz; Lahr, Brian D.; Melton, L Joseph; Krause, Patricia K.; Maggi, Kristine; Talley, Nicholas J.; Murray, Joseph A.

    2011-01-01

    Background The prevalence of diagnosed celiac disease is less than 1 in 2,000 in the United States, but screening studies undertaken in European and other populations have revealed a much higher prevalence. Objectives To determine the prevalence of celiac disease and the utility of screening in the general adult population of a geographically isolated area. Methods Serum tissue transglutaminase antibodies (tTG-IgA) were measured in volunteer health care participants aged 18 years and over at Annual Casper, Wyoming Blue Envelope Health Fair Blood Draw. Subjects with positive tTG-IgA tests had their endomysial IgA antibodies checked. Double positives were offered endoscopy with small bowel biopsy. All subjects completed a short GI symptom questionnaire. Results 3850 residents of the Natrona County had serologic evaluation for celiac disease, 34 of whom tested positive for both tTG and EMA IgA. Excluding three individuals with previous diagnosis of celiac disease, the overall prevalence of celiac serology positive in this community sample was 0.8%. All 31 subjects were offered a small bowel biopsy. Seventeen of the 18 biopsied subjects (94%) had at least partial villous atrophy. Symptoms that were reported by the fair attendees did not predict positivity. Conclusions Screening for celiac disease was widely accepted in this preventative healthcare setting. Undiagnosed celiac disease affects 1 in 126 individuals in this Wyoming community. Most were asymptomatic or had atypical presentations. Serologic testing can readily detect this disease in a general population. PMID:21364545

  6. Prevalence of celiac disease in Germany: A prospective follow-up study

    PubMed Central

    Kratzer, Wolfgang; Kibele, Monika; Akinli, Atilla; Porzner, Marc; Boehm, Bernhard O; Koenig, Wolfgang; Oeztuerk, Suemeyra; Mason, Richard A; Mao, Ren; Haenle, Mark H

    2013-01-01

    AIM: To determine the prevalence of celiac disease in a randomly selected population sample. METHODS: A total of 2157 subjects (1036 males; 1121 females) participating in a population-based cross-sectional study underwent laboratory testing for tissue transglutaminase and antibodies to immunoglobulin A, endomysium and antigliadin. In a second step, all subjects who had been examined serologically were surveyed using a questionnaire that included questions specific to celiac disease. Subjects with positive antibody titers and those with histories positive for celiac disease then underwent biopsy. At the first follow up, antibody titers were again determined in these subjects and subjects were questioned regarding symptoms specific for celiac disease and disorders associated with celiac disease. The second follow up consisted of a telephone interview with subjects positive for celiac disease. RESULTS: Antibody tests consistent with celiac disease were reported in eight subjects, corresponding to an overall prevalence of 1:270 (8/2157). The prevalence among women was 1:224 and 1:518 in men. Classical symptoms were observed in 62.5% of subjects. Atypical celiac disease was present in 25.0%, and transient celiac disease in 12.5%. False-negative test results were returned in three subjects. This yields a sensitivity and specificity of 62.5% and 50.0%, respectively, for tissue transglutaminase immunoglobulin-A antibody; of 62.5% and 71.4% respectively, for endomysium antibody; and of 62.5% and 71.4%, respectively, for antigliadin antibody. CONCLUSION: The prevalence rate in our collective lies within the middle tertile of comparable studies in Europe. The use of a single antibody test for screening purposes must be called into question. PMID:23674868

  7. 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

  8. Ages of celiac disease: From changing environment to improved diagnostics

    PubMed Central

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-01-01

    From the time of Gee’s landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic “gluten infection”. The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed. PMID:21990947

  9. Celiac disease biodetection using lossy-mode resonances generated in tapered single-mode optical fibers

    NASA Astrophysics Data System (ADS)

    Socorro, A. B.; Corres, J. M.; Del Villar, I.; Matias, I. R.; Arregui, F. J.

    2014-05-01

    This work presents the development and test of an anti-gliadin antibodies biosensor based on lossy mode resonances (LMRs) to detect celiac disease. Several polyelectrolites were used to perform layer-by-layer assembly processes in order to generate the LMR and to fabricate a gliadin-embedded thin-film. The LMR shifted 20 nm when immersed in a 5 ppm anti-gliadin antibodies-PBS solution, what makes this bioprobe suitable for detecting celiac disease. This is the first time, to our knowledge, that LMRs are used to detect celiac disease and these results suppose promising prospects on the use of such phenomena as biological detectors.

  10. Collagenous gastritis associated with lymphocytic gastritis and celiac disease.

    PubMed

    Stancu, M; De Petris, G; Palumbo, T P; Lev, R

    2001-12-01

    Collagenous gastritis is a rare disorder, with only 8 cases reported in the literature, 2 in children and 6 in adults. We report an additional case of collagenous gastritis in a 42-year-old man with celiac disease. A thickened (>10 microm) subepithelial collagen band with entrapped capillaries, fibroblasts, and inflammatory cells was seen in the stomach, associated with lymphocytic gastritis. The duodenal mucosa showed severe villous atrophy but no subepithelial collagen deposition. No evidence of lymphocytic or collagenous colitis was found in the colon. The patient became symptom-free on a gluten exclusion diet and showed partial improvement of histopathologic findings after 3 months. Collagenous gastritis is a rare disease, but a wider recognition of its histopathologic features and clinical associations may bring more cases to light and provide additional clues in determining its etiology and pathogenesis. PMID:11735694

  11. Galactosylation of serum IgA1 O-glycans in celiac disease.

    PubMed

    Lindfors, Katri; Suzuki, Hitoshi; Novak, Jan; Collin, Pekka; Saavalainen, Päivi; Koskinen, Lotta L E; Mäki, Markku; Kaukinen, Katri

    2011-02-01

    In celiac disease, gluten ingestion provokes small-bowel mucosal injury and production of IgA autoantibodies against transglutaminase 2 (TG2). It has been suggested that in celiac patients IgA could mediate the transepithelial passage of gluten peptides in a mechanism involving the transferrin receptor. As IgA1 with galactose-deficient O-linked glycans has elevated affinity for the transferrin receptor, we assessed whether total serum IgA1 and IgA1 anti-TG2 autoantibodies in celiac patients are aberrantly glycosylated. We report that males with celiac disease have higher total serum levels of galactose-deficient IgA1 than non-celiac males. Furthermore, O-glycans of the disease-specific TG2 IgA1 autoantibodies in celiac patients exhibited elevated galactose deficiency. A gluten-free diet had no effect on the total serum levels of galactose-deficient IgA1, whereas the amount of galactose-deficient anti-TG2 IgA1 decreased. Thus, the undergalactosylated IgA1 molecules are not pathognomonic for celiac disease, but galactose deficiency in IgA1 could be an aggravating factor.

  12. Celiac disease in children and adolescents with Hashimoto Thyroiditis

    PubMed Central

    Tuhan, Hale; Işık, Sakine; Abacı, Ayhan; Şimşek, Erdem; Anık, Ahmet; Anal, Özden; Böber, Ece

    2016-01-01

    Aim: The aim of this study was to evaluate clinical and laboratory findings and determine the prevalence of celiac disease (CD) in children with Hashimoto thyroiditis (HT). Material and Methods: The data of a total of 80 patients with positive anti-thyroid antibodies who were aged between 6 and 17.9 years were retrospectively studied. Age, gender, complaints at the time of presentation, family history of thyroid disorders, clinical and laboratory findings were recorded. The levels of thyrotropin, free thyroxin, thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies), immunoglobulin A (IgA), anti-tissue transglutaminase antibodies (IgA-tTG), and thyroid ultrasonography findings were enrolled. Results: Eighty patients (65 females (81.2%) and 15 males (18,8%)) were included in the study. Family history of thyroid disease was present in 38 (47.5%) patients. The most common complaints at the time of presentation were goiter (%30) and weight gain (%25). Forty three (53.8%), 23 (28.7%), and 14 (17.5%) patients presented with euthyroidism, subclinical hypothyroidism and obvious hypothyroidism. Thirty seven (46.2%) patients had goiter. IgA-tTG was found to be positive after a diagnosis of HT was made in only one patient (1.25%) and the diagnosis of CD was confirmed when intestinal biopsy of this patient revealed villus atrophy, crypt hyperplasia and increase in the intraepithelial lymphocyte count. Conclusions: In our study, it was found that the most common complaints at presentation in patients with a diagnosis of hashimoto thyroiditis included goiter, weakness and weight gain and the prevalence of celiac diseases was found to be 1.25% (1/80). This study shows that the prevalence of CD in patients with a diagnosis of HT is higher compared to the prevalence in the healthy pediatric population. PMID:27489467

  13. Celiac Disease in a Predisposed Subject (HLA-DQ2.5) with Coexisting Graves' Disease.

    PubMed

    Hwang, In Kyoung; Kim, Seon Hye; Lee, Unjoo; Chin, Sang Ouk; Rhee, Sang Youl; Oh, Seungjoon; Woo, Jeong Taek; Kim, Sung Woon; Kim, Young Seol; Chon, Suk

    2015-03-27

    Celiac disease is an intestinal autoimmune disorder, triggered by ingestion of a gluten-containing diet in genetically susceptible individuals. The genetic predisposition is related to human leukocyte antigen (HLA) class II genes, especially HLA-DQ2-positive patients. The prevalence of celiac disease has been estimated to be ~1% in Europe and the USA, but it is rarer and/or underdiagnosed in Asia. We report a case of celiac disease in a predisposed patient, with a HLA-DQ2 heterodimer, and Graves' disease that was treated successfully with a gluten-free diet. A 47-year-old woman complained of persistent chronic diarrhea and weight loss over a 9 month period. Results of all serological tests and stool exams were negative. However, the patient was found to carry the HLA DQ2 heterodimer. Symptoms improved after a gluten-free diet was initiated. The patient has been followed and has suffered no recurrence of symptoms while on the gluten-free diet. An overall diagnosis of celiac disease was made in a genetically predisposed patient (HLA-DQ2 heterodimer) with Graves' disease.

  14. 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.

  15. Origin of celiac disease: how old are predisposing haplotypes?

    PubMed

    Gasbarrini, Giovanni; Rickards, Olga; Martínez-Labarga, Cristina; Pacciani, Elsa; Chilleri, Filiberto; Laterza, Lucrezia; Marangi, Giuseppe; Scaldaferri, Franco; Gasbarrini, Antonio

    2012-10-01

    We recently presented the case of a first century AD young woman, found in the archaeological site of Cosa, showing clinical signs of malnutrition, such as short height, osteoporosis, dental enamel hypoplasia and cribra orbitalia, indirect sign of anemia, all strongly suggestive for celiac disease (CD). However, whether these findings were actually associated to CD was not shown based on genetic parameters. To investigate her human leukocyte antigen (HLA) class II polymorphism, we extracted DNA from a bone sample and a tooth and genotyped HLA using three HLA-tagging single nucleotide polymorphisms for DQ8, DQ2.2 and DQ2.5, specifically associated to CD. She displayed HLA DQ 2.5, the haplotype associated to the highest risk of CD. This is the first report showing the presence of a HLA haplotype compatible for CD in archaeological specimens. PMID:23066327

  16. Prevalence of celiac disease in patients with severe food allergy.

    PubMed

    Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

    2015-10-01

    The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.

  17. Origin of celiac disease: How old are predisposing haplotypes?

    PubMed Central

    Gasbarrini, Giovanni; Rickards, Olga; Martínez-Labarga, Cristina; Pacciani, Elsa; Chilleri, Filiberto; Laterza, Lucrezia; Marangi, Giuseppe; Scaldaferri, Franco; Gasbarrini, Antonio

    2012-01-01

    We recently presented the case of a first century AD young woman, found in the archaeological site of Cosa, showing clinical signs of malnutrition, such as short height, osteoporosis, dental enamel hypoplasia and cribra orbitalia, indirect sign of anemia, all strongly suggestive for celiac disease (CD). However, whether these findings were actually associated to CD was not shown based on genetic parameters. To investigate her human leukocyte antigen (HLA) class II polymorphism, we extracted DNA from a bone sample and a tooth and genotyped HLA using three HLA-tagging single nucleotide polymorphisms for DQ8, DQ2.2 and DQ2.5, specifically associated to CD. She displayed HLA DQ 2.5, the haplotype associated to the highest risk of CD. This is the first report showing the presence of a HLA haplotype compatible for CD in archaeological specimens. PMID:23066327

  18. Celiac disease: Autoimmunity in response to food antigen.

    PubMed

    Stamnaes, J; Sollid, L M

    2015-09-01

    Celiac disease (CD) is an increasingly common disease of the small intestine that occurs in genetically susceptible subjects by ingestion of cereal gluten proteins. Gluten is highly abundant in the modern diet and well tolerated by most individuals. In CD, however, an erroneous but highly specific, adaptive immune response is mounted toward certain parts of the gluten proteome. The resulting intestinal destruction is reversible and resolved upon removal of gluten from the diet. Post-translational modification (deamidation) of gluten peptides by transglutaminase 2 (TG2) is essential for the peptides to act as HLA-DQ-restricted T-cell antigens. Characteristically, deamidated gluten and the self-protein TG2 both become targets of highly disease specific B-cell responses. These antibodies share several peculiar characteristics despite being directed against vastly different antigens, which suggests a common mechanism of development. Importantly, no clear function has been ascribed to the antibodies and their contribution to disease may relate to their function as antigen receptors of the B cells rather than as soluble immunoglobulins. Adaptive immunity against gluten and TG2 appears not to be sufficient for establishment of the disease lesion, and it has been suggested that stress responses in the intestinal epithelium are essential for the development of full-blown disease and tissue damage. In this review we will summarize current concepts of the immune pathology of CD with particular focus on recent advances in our understanding of disease specific B-cell responses.

  19. Salivary Microbiota and Metabolome Associated with Celiac Disease

    PubMed Central

    Francavilla, Ruggiero; Ercolini, Danilo; Piccolo, Maria; Vannini, Lucia; Siragusa, Sonya; De Filippis, Francesca; De Pasquale, Ilaria; Di Cagno, Raffaella; Di Toma, Michele; Gozzi, Giorgia; Serrazanetti, Diana I.; Gobbetti, Marco

    2014-01-01

    This study aimed to investigate the salivary microbiota and metabolome of 13 children with celiac disease (CD) under a gluten-free diet (treated celiac disease [T-CD]). The same number of healthy children (HC) was used as controls. The salivary microbiota was analyzed by an integrated approach using culture-dependent and -independent methods. Metabolome analysis was carried out by gas chromatography-mass spectrometry–solid-phase microextraction. Compared to HC, the number of some cultivable bacterial groups (e.g., total anaerobes) significantly (P < 0.05) differed in the saliva samples of the T-CD children. As shown by community-level catabolic profiles, the highest Shannon's diversity and substrate richness were found in HC. Pyrosequencing data showed the highest richness estimator and diversity index values for HC. Levels of Lachnospiraceae, Gemellaceae, and Streptococcus sanguinis were highest for the T-CD children. Streptococcus thermophilus levels were markedly decreased in T-CD children. The saliva of T-CD children showed the largest amount of Bacteroidetes (e.g., Porphyromonas sp., Porphyromonas endodontalis, and Prevotella nanceiensis), together with the smallest amount of Actinobacteria. T-CD children were also characterized by decreased levels of some Actinomyces species, Atopobium species, and Corynebacterium durum. Rothia mucilaginosa was the only Actinobacteria species found at the highest level in T-CD children. As shown by multivariate statistical analyses, the levels of organic volatile compounds markedly differentiated T-CD children. Some compounds (e.g., ethyl-acetate, nonanal, and 2-hexanone) were found to be associated with T-CD children. Correlations (false discovery rate [FDR], <0.05) were found between the relative abundances of bacteria and some volatile organic compounds (VOCs). The findings of this study indicated that CD is associated with oral dysbiosis that could affect the oral metabolome. PMID:24657864

  20. Fatal Streptococcus pneumoniae Sepsis in a Patient With Celiac Disease-Associated Hyposplenism

    PubMed Central

    Ouseph, Madhu M.; Simons, Malorie; Treaba, Diana O.; Yakirevich, Evgeny; Green, Peter H.; Bhagat, Govind; Moss, Steven F.

    2016-01-01

    We present a 59-year-old male with poorly controlled celiac disease (CD) and fatal Streptococcus pneumoniae sepsis, describe the morphologic findings, and stress the need for monitoring splenic function and pneumococcal vaccination in these patients. PMID:27761478

  1. Prevalence of celiac disease and celiac autoimmunity in the Toba native Amerindian community of Argentina

    PubMed Central

    Vázquez, Horacio; de la Paz Temprano, María; Sugai, Emilia; Scacchi, Stella M; Souza, Cecilia; Cisterna, Daniel; Smecuol, Edgardo; Moreno, María Laura; Longarini, Gabriela; Mazure, Roberto; Bartellini, María A; Verdú, Elena F; González, Andrea; Mauriño, Eduardo; Bai, Julio C

    2015-01-01

    BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD. OBJECTIVE: To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission. METHODS: An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies. RESULTS: A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors’ laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype. CONCLUSION: The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis. PMID:26207618

  2. Hemoptysis in patients of celiac disease with disproportionately severe anemia: tip of the iceberg?

    PubMed Central

    2013-01-01

    Idiopathic Pulmonary Hemosiderosis (IPH) is characterized by the triad of iron deficiency anemia, pulmonary infiltrates and haemoptysis with no recognizable cause. Since the first description of its association with Celiac Disease (CD) by Lane and Hamilton in 1971, only a few isolated cases have been reported in literature. Although it has been considered an uncommon association of two disease entities, recent reports indicate that prevalence of celiac disease is as high as one percent. Further, individually both celiac disease and IPH are known to present as refractory anemia only. We are reporting a young adult with Lane Hamilton Syndrome, who realized that he was having significant gastrointestinal complaints only when they disappeared on gluten free diet (GFD). This case report reiterates the fact that celiac disease should be considered in all patients of IPH because of the therapeutic implications. Further on review of literature, we believe that covert hemoptysis may be responsible for disproportionately severe anemia in patients of celiac disease. Thus, prevalence of this association may be more than currently believed. Further research in this regard may improve our understanding of pathogenesis of celiac disease. PMID:23514358

  3. Age-related differences in celiac disease: Specific characteristics of adult presentation

    PubMed Central

    Vivas, Santiago; Vaquero, Luis; Rodríguez-Martín, Laura; Caminero, Alberto

    2015-01-01

    Celiac disease may appear both in early childhood and in elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients. PMID:26558154

  4. Shared and Distinct Genetic Variants in Type 1 Diabetes and Celiac Disease

    PubMed Central

    Smyth, Deborah J; Plagnol, Vincent; Walker, Neil M; Cooper, Jason D; Downes, Kate; Yang, Jennie HM; Howson, Joanna MM; Stevens, Helen; McManus, Ross; Wijmenga, Cisca; Heap, Graham A.; Dubois, Patrick C.; Clayton, David G.; Hunt, Karen A; van Heel, David A; Todd, John A

    2009-01-01

    BACKGROUND The inflammatory disorders type 1 diabetes (T1D) and celiac disease co-segregate in populations, suggesting a common genetic origin. Both are associated with the HLA class II genes on chromosome 6p21, and the present paper tested whether non-HLA loci are shared. METHODS We evaluated eight celiac disease risk loci in T1D by genotyping and statistical analyses of 8,064 T1D cases, 9,339 controls and 2,519 families. We also investigated 18 T1D loci in 2,560 celiac disease cases and 9,339 controls. RESULTS Three celiac disease loci, listed as chromosome/candidate gene: 1q31/RGS1, 2q12/IL18RAP and 6q25/TAGAP, were associated with T1D (P < 10−4). The 3p21/CCR5 32 base pair insertion/deletion variant was newly identified as a T1D locus (P = 1.81 × 10−8), and was also associated with celiac disease, as were 18p11/PTPN2 and 2q33/CTLA4, bringing the total loci shared to seven, including 12q24/SH2B3. The 2q12/IL18RAP and 6q25/TAGAP allele associations were in the opposite direction in T1D as compared to celiac disease. Distinct effects included 11p15/INS, 10p15/IL2RA and 1q13/PTPN22 in T1D and 3q25/IL12A and 3q28/LPP in celiac disease. CONCLUSIONS Genetic susceptibility to T1D and celiac disease shares common alleles. These data suggest that common biological mechanisms, such as autoimmunity related tissue damage and intolerance to dietary antigens may be a feature of T1D. PMID:19073967

  5. Risk of Thyroid Cancer in a Nationwide Cohort of Patients with Biopsy-Verified Celiac Disease

    PubMed Central

    Lebwohl, Benjamin; Kämpe, Olle; Murray, Joseph A.; Green, Peter H.; Ekbom, Anders

    2013-01-01

    Background In earlier studies based on selected populations, the relative risk for thyroid cancer in celiac disease has varied between 0.6 and 22.5. We aimed to test this relationship in a population-based setting. Methods We collected small intestinal biopsy report data performed in 1969–2008 from all 28 Swedish pathology departments. 29,074 individuals with celiac disease (villous atrophy; Marsh histopathology stage III) were matched for sex, age, calendar year, and county to 144,440 reference individuals from the Swedish general population. Through Cox regression, we then estimated hazard ratios (HRs) and confidence intervals (CIs) for any thyroid cancer and papillary thyroid cancer (defined according to relevant pathology codes in the Swedish Cancer Register) in patients with celiac disease. Results During follow-up, any thyroid cancer developed in seven patients with celiac disease (expected=12) and papillary thyroid cancer developed in five patients (expected=7). Celiac disease was not associated with an increased risk of any thyroid cancer (HR 0.6 [CI 0.3–1.3]) or of papillary thyroid cancer (HR 0.7 [CI 0.3–1.8]). All cases of thyroid cancer in celiac disease occurred in female patients. Risk estimates were similar before and after the year 2000 and independent of age at celiac diagnosis (≤24 years vs. ≥25 years). Conclusions We conclude that, in the Swedish population, there is no increased risk of thyroid cancer in patients with celiac disease. This differs from what has been reported in smaller studies in Italy and the United States. PMID:23281890

  6. Frequency of Celiac Disease In Children With Chronic Functional Constipation in Shiraz-Iran.

    PubMed

    Dehghani, Seyed Mohsen; Ehsaei, Zahra; Honar, Naser; Javaherizadeh, Hazhir

    2015-07-01

    BACKGROUND Celiac disease is an autoimmune mediated small intestine inflammation which occurs due to hypersensitivity reaction to gluten and related proteins in diet in genetically predisposed individuals. Prevalence of celiac among the population is about 0.5 - 1 % in most countries. Frequency of celiac disease in children is the subject of a few research. In this study, we aim to determine the frequency of celiac disease in patients presenting with functional constipation. METHODS This cross-sectional study was conducted on children referring to Imam Reza Clinic, affiliated to Shiraz University of Medical Sciences during one year starting from 2011, March 20. One hundred and one children 2-18 years of age with constipation for more than 2 months according to ROME III criteria. The entire participants underwent serologic studies of Total IgA and IgA TTG. Serum IgG TTG was measured in cases with reported values of Total IgA below the lowest normal limits. Moreover, endoscopic biopsy of the small intestine was also performed for patients with positive serology. RESULTS Of all the 101 studied participants, only four individuals (3.96 %) had positive test results for IgA TTG ( potential celiac disease). one of these patients refused to do endoscopy and endoscopic small intestine biopsy was performed for 3 patients. Two of them had normal pathology and one of them(0.99 %) was confirmed for celiac disease. CONCLUSION The frequency of celiac disease in children with chronic constipation is slightly higher than general population but without significant difference( 0.99% VS 0.6% ; p=0.64). So the screening serologic test for celiac disease is not recommended in children with chronic constipation.

  7. 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. PMID:26259710

  8. 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.

  9. Immune Development and Intestinal Microbiota in Celiac Disease

    PubMed Central

    Pozo-Rubio, Tamara; Olivares, Marta; Nova, Esther; De Palma, Giada; Mujico, Jorge R.; Ferrer, Maria Desamparados; Marcos, Ascensión; Sanz, Yolanda

    2012-01-01

    Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding), infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance. PMID:23008734

  10. Managing the pediatric patient with celiac disease: a multidisciplinary approach

    PubMed Central

    Isaac, Daniela Migliarese; Wu, Jessica; Mager, Diana R; Turner, Justine M

    2016-01-01

    Celiac disease (CD) is an autoimmune reaction to gluten, leading to intestinal inflammation, villous atrophy, and malabsorption. It is the most common autoimmune gastrointestinal disorder, with an increasing prevalence. A life-long gluten-free diet (GFD) is an effective treatment to alleviate symptoms, normalize autoantibodies, and heal the intestinal mucosa in patients with CD. Poorly controlled CD poses a significant concern for ongoing malabsorption, growth restriction, and the long-term concern of intestinal lymphoma. Achieving GFD compliance and long-term disease control poses a challenge, with adolescents at particular risk for high rates of noncompliance. Attention has turned toward innovative management strategies to improve adherence and achieve better disease control. One such strategy is the development of multidisciplinary clinic approach, and CD is a complex life-long disease state that would benefit from a multifaceted team approach as recognized by multiple national and international bodies, including the National Institutes of Health. Utilizing the combined efforts of the pediatric gastroenterologist, registered dietitian, registered nurse, and primary care provider (general practitioner or general pediatrician) in a CD multidisciplinary clinic model will be of benefit for patients and families in optimizing diagnosis, provision of GFD teaching, and long-term adherence to a GFD. This paper discusses the benefits and proposed structure for multidisciplinary care in improving management of CD. PMID:27785047

  11. Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis

    PubMed Central

    Matthias, Torsten

    2015-01-01

    The incidence of celiac disease is increasing worldwide, and human tissue transglutaminase has long been considered the autoantigen of celiac disease. Concomitantly, the food industry has introduced ingredients such as microbial transglutaminase, which acts as a food glue, thereby revolutionizing food qualities. Several observations have led to the hypothesis that microbial transglutaminase is a new environmental enhancer of celiac disease. First, microbial transglutaminase deamidates/transamidates glutens such as the endogenous human tissue transglutaminase. It is capable of crosslinking proteins and other macromolecules, thereby changing their antigenicity and resulting in an increased antigenic load presented to the immune system. Second, it increases the stability of protein against proteinases, thus diminishing foreign protein elimination. Infections and the crosslinked nutritional constituent gluten and microbial transglutaminase increase the permeability of the intestine, where microbial transglutaminases are necessary for bacterial survival. The resulting intestinal leakage allows more immunogenic foreign molecules to induce celiac disease. The increased use of microbial transglutaminase in food processing may promote celiac pathogenesis ex vivo, where deamidation/transamidation starts, possibly explaining the surge in incidence of celiac disease. If future research substantiates this hypothesis, the findings will affect food product labeling, food additive policies of the food industry, and consumer health education. PMID:26084478

  12. 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.

  13. 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

  14. Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis.

    PubMed

    Lerner, Aaron; Matthias, Torsten

    2015-08-01

    The incidence of celiac disease is increasing worldwide, and human tissue transglutaminase has long been considered the autoantigen of celiac disease. Concomitantly, the food industry has introduced ingredients such as microbial transglutaminase, which acts as a food glue, thereby revolutionizing food qualities. Several observations have led to the hypothesis that microbial transglutaminase is a new environmental enhancer of celiac disease. First, microbial transglutaminase deamidates/transamidates glutens such as the endogenous human tissue transglutaminase. It is capable of crosslinking proteins and other macromolecules, thereby changing their antigenicity and resulting in an increased antigenic load presented to the immune system. Second, it increases the stability of protein against proteinases, thus diminishing foreign protein elimination. Infections and the crosslinked nutritional constituent gluten and microbial transglutaminase increase the permeability of the intestine, where microbial transglutaminases are necessary for bacterial survival. The resulting intestinal leakage allows more immunogenic foreign molecules to induce celiac disease. The increased use of microbial transglutaminase in food processing may promote celiac pathogenesis ex vivo, where deamidation/transamidation starts, possibly explaining the surge in incidence of celiac disease. If future research substantiates this hypothesis, the findings will affect food product labeling, food additive policies of the food industry, and consumer health education.

  15. 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. PMID:27446825

  16. Prevalence of Celiac Disease in Children with Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Zahmatkeshan, Mozhgan; Fallahpoor, Mahsa; Amoozgar, Hamid

    2014-01-01

    Objective: This study aimed to evaluate the prevalence of celiac disease (CD) in the patients with dilated cardiomyopathy (DCM). Simultaneous presentation of these two diseases has been recently reported in some studies; however, few researches have been done on children. The sooner CD is diagnosed, the better the prognosis will be, especially in the patients with a chronic disease like DCM. Methods: In this study, 82 cases were screened for CD by measuring the level of anti-body against transglutaminase (anti tTG). These cases included 41 patients with DCM labeled according to clinical evaluation and echocardiography and 41 healthy children who had been referred for routine checkup. All the patients were between 1 and 18 years old. The expired patients and those with previous diagnosis of CD were excluded from the study. Besides, the patients with positive antibody results underwent intestinal biopsy to match the serology findings with histopathology of CD in the intestine. Finally, the data were analyzed by the SPSS statistical software (v. 16) and through t-test and Pearson correlation coefficient. Findings: According to the findings, 1/41 (2.5%) DCM cases had positive tTG antibody level and negative intestinal biopsy which is classified as potential CD in the children with DCM. In addition, 7/41 (17%) patients had borderline anti body level. A direct correlation was observed between age and anti tTG level. Conclusion: It is beneficial to assess CD in DCM children with unknown cause. PMID:25793066

  17. Early infections are associated with increased risk for celiac disease: an incident case-referent study

    PubMed Central

    2012-01-01

    Background Celiac disease is defined as a ‘chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Sweden has experienced an “epidemic” of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic. Methods A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child’s general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents. Results Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001). Conclusion This study suggests that having repeated

  18. Acute abdomen in adult Celiac disease: an intestinal intussusception case.

    PubMed

    Makay, Ozer; Kazimi, Mircelal; Doğanavşargil, Başak; Osmanoğlu, Necla; Yilmaz, Mustafa

    2007-06-01

    It is well known that half of the cases admitted to hospital emergency services complain of abdominal pain and that nearly half of these cases are diagnosed with nonspecific abdominal pain. The population of patients with celiac sprue is rarely encountered at the emergency room. Although acute abdominal pain is rarely seen in adult celiac sprue, it should be added to the differential diagnosis. It should also be remembered that acute abdominal pain in these patients could be originating from perforation, intussusceptions and/or intestinal lymphoma. Herein we report a case of adult celiac sprue where successful surgical exploration was carried out because of entero-enteral intussusception. PMID:17602358

  19. 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…

  20. Diagnostic yield of endoscopic markers for celiac disease

    PubMed Central

    Balaban, DV; Popp, A; Vasilescu, F; Haidautu, D; Purcarea, RM; Jinga, M

    2015-01-01

    Rationale: In the setting of open access endoscopy, the recognition of suggestive endoscopic features in the duodenum can select patients with probability of celiac disease (CD). This could add to the current efforts to increase the diagnostic rate of this disease. Aim: The aim of this study was to evaluate the diagnostic accuracy of these markers for CD in an adult population undergoing endoscopy, without a prior serological testing. Methods and Results: Over a period of 3 years, between June 2012 and 2015, all the patients who underwent upper gastrointestinal endoscopy and presented one or more of the endoscopic markers consistent with CD, or those suspected for CD, irrespective of the presence of these markers, were included. Sensitivity, specificity, positive and negative predictive values were calculated for these markers in CD diagnosis. Among the 182 patients, 56.04% were females, with a mean age of 47.6 ± 13.9 years. 20/182 (10.99%) had a final diagnosis of CD. The presence of any endoscopic marker had a high sensitivity (95%) and a negative predictive value (98.41%). Bulb atrophy and reduced folds in the descending duodenum had a low diagnostic accuracy, while scalloping, mosaic pattern and fissures were highly specific for CD (98.77%, 99.38% and 98.77%) and their presence greatly increased the probability of CD, with a positive likelihood ratio of 24.3, 24.3 and 12.15, respectively. Discussions: A wide set of endoscopic markers, including the duodenal bulb, were evaluated in this study. Our results showed that the endoscopy with a careful examination of the duodenum is a sensitive indicator for CD. Abbreviations: CD = celiac disease, GI = gastrointestinal, VA = villous atrophy, NSAID = nonsteroidal anti-inflammatory drug, Sn = sensitivity, Sp = specificity, PPV = positive predictive value, NPV = negative predictive value, AUC = area under the curve, ROC = receiver operating characteristics, WLE = white light endoscopy, NBI = narrow band imaging, t

  1. Dietary compliance in Iranian children and adolescents with celiac disease

    PubMed Central

    Taghdir, Maryam; Honar, Naser; Mazloomi, Seyed Mohammad; Sepandi, Mojtaba; Ashourpour, Mahkameh; Salehi, Musa

    2016-01-01

    Introduction Celiac disease (CD) is caused due to intake of gluten, a protein component in wheat, barley, and rye. The only treatment currently available for CD is strict lifetime adherence to a gluten-free diet (GFD) which is a diet that excludes wheat, barley, and rye. There is limited information on barriers to following a GFD. The present study aimed to investigate the compliance with a GFD, barriers to compliance, and the impact of compliance on the quality of life (QOL) in Iranian children and adolescents suffering from CD. Methods In this cross-sectional study, a total of 65 known cases of CD (both males and females), diagnosed in Namazi Hospital, a large referral center in south of Iran, selected by census were studied in 2014. Dietary compliance was assessed using a questionnaire. A disease-specific QOL questionnaire for children with CD (the celiac disease DUX [CDDUX]) was used. Comparisons between categorical variables were performed using chi-square test. Results Sixty-five patients, 38 females (58.5%) and 27 (41.5%) males, were surveyed. Mean (± standard deviation [SD]) age of the respondents was 11.3 (±3.8) years. Dietary compliance was reported by 35 (53.8%) patients. The mean (± SD) CDDUX score was higher in dietary-compliant patients (33.5 [±19.4] vs 26.7 [±13.6], respectively, P=0.23). The score of CDDUX in parents of patients in dietary-compliant group was more than the noncompliant patients (28.1 [±13.5] vs 22.1 [±14], respectively, P=0.1). Barriers to noncompliance were poor or unavailability (100%), high cost (96.9%), insufficient labeling (84.6%), poor palatability (76.9%), and no information (69.23%). Conclusion Approximately half of the patients with CD reported dietary compliance. Poor or unavailability was found to be the most important barrier contributing to noncompliance. The QOL was better in compliant patients. Proposed strategies to improve compliance are greater availability of gluten-free products, better food labeling, and

  2. Celiac disease prevalence in Brazilian dilated cardiomyopathy patients.

    PubMed

    De Bem, Ricardo Schmit T; Da Ro Sa Utiyama, Shirley Ramos; Nisihara, Renato Mitsunori; Fortunato, Jerônimo Antônio; Tondo, Josué Augusto; Carmes, Eliane Ribeiro; Souza, Raquel Almada E; Pisani, Julio César; Amarante, Heda Maria Barska Dos Santos

    2006-05-01

    Celiac disease (CD) is a permanent condition of gluten intolerance and a number of autoimmune diseases have been associated with it. In the past few years, a relation between CD and dilated cardiomyopathy (CM) was described in Europe and United States. The aim of this study was to evaluate the prevalence of CD among south Brazilian precardiac transplant patients with advanced CM. A total of 74 patients on a list for heart transplantation were evaluated for the presence CD. The presence of anti-endomisial antibody (IgA-EmA) was determined by indirect immunofluorescence and for the anti-transglutaminase antibody (IgA anti-h-tTG) by ELISA. Serologically positive patients were submitted to upper endoscopy with intestinal biopsy. Two individuals (2.63%) were positive for IgA-EmA and 5 (6.75%) for IgA anti-h-tTG; 1 (1.35%) had both tests positive. Histologic confirmation of CD occurred only in the IgA-EmA positive patients. In conclusion, data from the present study allows recommend the screening for CD in patients with CM using IgA-EmA test as the method of choice. PMID:16758314

  3. Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy

    PubMed Central

    Petrarca, Laura; Nenna, Raffaella; Mastrogiorgio, Gerarda; Florio, Matteo; Brighi, Manuela; Pontone, Stefano

    2014-01-01

    The prevalence of dyspepsia is up to 40% in population-based study. Functional dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related functional disorder, characterized by the presence of persistent or recurrent pain or discomfort centered in the upper abdomen, neither relief by defecation, nor association with the onset of a change in stool frequency or form. Celiac disease (CD) is a common autoimmune enteropathy, with a prevalence around 1% in the general population. Its diagnosis includes a serological screening and an upper gastrointestinal endoscopy with multiple biopsies. Gluten-free diet is the only effective treatment. CD diagnosis is often delayed in asymptomatic patients or in individuals with less clinical gastrointestinal symptoms. Several studies performed coeliac disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsy-proved prevalence that ranged from 0.5% to 2%. The typical endoscopic markers of villous atrophy are not sufficiently sensitive, so some endoscopic techniques, such as “water immersion” and confocal endomicroscopy were proposed to improve the diagnostic sensitivity and target biopsies. A recent meta-analysis estimated that the prevalence of CD was higher in patients with dyspepsia, but not in a statistically significant way. However this assumption should be confirmed further larger studies. PMID:25332916

  4. Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy.

    PubMed

    Petrarca, Laura; Nenna, Raffaella; Mastrogiorgio, Gerarda; Florio, Matteo; Brighi, Manuela; Pontone, Stefano

    2014-09-26

    The prevalence of dyspepsia is up to 40% in population-based study. Functional dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related functional disorder, characterized by the presence of persistent or recurrent pain or discomfort centered in the upper abdomen, neither relief by defecation, nor association with the onset of a change in stool frequency or form. Celiac disease (CD) is a common autoimmune enteropathy, with a prevalence around 1% in the general population. Its diagnosis includes a serological screening and an upper gastrointestinal endoscopy with multiple biopsies. Gluten-free diet is the only effective treatment. CD diagnosis is often delayed in asymptomatic patients or in individuals with less clinical gastrointestinal symptoms. Several studies performed coeliac disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsy-proved prevalence that ranged from 0.5% to 2%. The typical endoscopic markers of villous atrophy are not sufficiently sensitive, so some endoscopic techniques, such as "water immersion" and confocal endomicroscopy were proposed to improve the diagnostic sensitivity and target biopsies. A recent meta-analysis estimated that the prevalence of CD was higher in patients with dyspepsia, but not in a statistically significant way. However this assumption should be confirmed further larger studies. PMID:25332916

  5. Celiac disease diagnosis and gluten-free food analytical control.

    PubMed

    da Silva Neves, Marta Maria Pereira; González-Garcia, Maria Begoña; Nouws, Hendrikus Petrus Antonius; Delerue-Matos, Cristina; Santos-Silva, Alice; Costa-García, Agustín

    2010-07-01

    Celiac disease (CD) is an autoimmune enteropathy, characterized by an inappropriate T-cell-mediated immune response to the ingestion of certain dietary cereal proteins in genetically susceptible individuals. This disorder presents environmental, genetic, and immunological components. CD presents a prevalence of up to 1% in populations of European ancestry, yet a high percentage of cases remain underdiagnosed. The diagnosis and treatment should be made early since untreated disease causes growth retardation and atypical symptoms, like infertility or neurological disorders. The diagnostic criteria for CD, which requires endoscopy with small bowel biopsy, have been changing over the last few decades, especially due to the advent of serological tests with higher sensitivity and specificity. The use of serological markers can be very useful to rule out clinical suspicious cases and also to help monitor the patients, after adherence to a gluten-free diet. Since the current treatment consists of a life-long gluten-free diet, which leads to significant clinical and histological improvement, the standardization of an assay to assess in an unequivocal way gluten in gluten-free foodstuff is of major importance.

  6. Classification of videocapsule endoscopy image patterns: comparative analysis between patients with celiac disease and normal individuals

    PubMed Central

    2010-01-01

    Background Quantitative disease markers were developed to assess videocapsule images acquired from celiac disease patients with villous atrophy, and from control patients. Method Capsule endoscopy videoclip images (576 × 576 pixels) were acquired at 2/second frame rate (11 celiacs, 10 controls) at regions: 1. bulb, 2. duodenum, 3. jejunum, 4. ileum and 5. distal ileum. Each of 200 images per videoclip (= 100s) were subdivided into 10 × 10 pixel subimages for which mean grayscale brightness level and its standard deviation (texture) were calculated. Pooled subimage values were grouped into low, intermediate, and high texture bands, and mean brightness, texture, and number of subimages in each band (nine features in all) were used for quantifying regions 1-5, and to determine the three best features for threshold and incremental learning classification. Classifiers were developed using 6 celiac and 5 control patients' data as exemplars, and tested on 5 celiacs and 5 controls. Results Pooled from all regions, the threshold classifier had 80% sensitivity and 96% specificity and the incremental classifier had 88% sensitivity and 80% specificity for predicting celiac versus control videoclips in the test set. Trends of increasing texture from regions 1 to 5 occurred in the low and high texture bands in celiacs, and the number of subimages in the low texture band diminished (r2 > 0.5). No trends occurred in controls. Conclusions Celiac videocapsule images have textural properties that vary linearly along the small intestine. Quantitative markers can assist in screening for celiac disease and localize extent and degree of pathology throughout the small intestine. PMID:20815911

  7. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen

    PubMed Central

    Elli, Luca; Rossi, Valentina; Conte, Dario; Ronchi, Anna; Tomba, Carolina; Passoni, Manuela; Bardella, Maria Teresa; Roncoroni, Leda; Guzzi, Gianpaolo

    2015-01-01

    Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were 2.4 ± 2.3/1.0 ± 1.4, 10.2 ± 6.7/2.2 ± 3.0 and 3.7 ± 2.7/1.3 ± 1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism. PMID:25802516

  8. An extended HLA-D region haplotype associated with celiac disease.

    PubMed Central

    Howell, M D; Smith, J R; Austin, R K; Kelleher, D; Nepom, G T; Volk, B; Kagnoff, M F

    1988-01-01

    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. We previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II beta-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. We now report the isolation of this beta-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP beta chain. This celiac disease-associated HLA-DP beta-chain gene was flanked by HLA-DP alpha-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP alpha-chain genes of celiac disease patients also were studied by RFLP analysis; 84% of HLA-DR3, -DQw2 patients had a 16-kb Xba I fragment that was present in only 36% of HLA-DR3, -DQw2 controls. Moreover, 79% of these patients had both alpha- and beta-chain polymorphisms in contrast to 27% of controls. Thus, celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP alpha- and beta-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion. Images PMID:2893373

  9. Managing Celiac Disease for Women: Implications for the Primary Care Provider.

    PubMed

    Peterson, Megan; Grossman, Sheila

    2016-01-01

    Although many people have symptoms of celiac disease, it can take a while to diagnose. Villous atrophy may be present long before any gastrointestinal symptoms. An important point to acknowledge is that celiac disease could be identified earlier in some women with a positive family history. The disease also could be the cause of some women's reproductive problems. Primary care providers, using comprehensive history taking, are in the unique position to identify individuals who may have celiac disease, assist women in gaining knowledge about a gluten-free diet, order diagnostic testing, and refer to a gastroenterologist. The positive change in fertility with a simultaneous improvement of nutrient deficiencies shortly after adopting a gluten-free diet indicates a possible link between such nutrients and sex hormone function. High levels of homocysteine, which can negatively impact fertility, have also been linked to individuals with problems, such as celiac disease, that decrease vitamin B12 absorption. The purpose of this article is to review the literature and the evidence-based care guidelines for comprehensive screening, diagnostics, and pathophysiology of celiac disease, with a specific focus on the female reproductive system, anemia management, and gluten-free diet integration. PMID:27258459

  10. Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease.

    PubMed

    Rey, Martial; Yang, Menglin; Lee, Linda; Zhang, Ye; Sheff, Joey G; Sensen, Christoph W; Mrazek, Hynek; Halada, Petr; Man, Petr; McCarville, Justin L; Verdu, Elena F; Schriemer, David C

    2016-08-02

    Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates, and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1.

  11. Non-dietary forms of treatment for adult celiac disease

    PubMed Central

    Freeman, Hugh James

    2013-01-01

    At present, treatment for celiac disease includes a strict gluten-free diet. Compliance, however, is difficult and gluten-free food products are costly, and, sometimes very inconvenient. A number of potential alternative measures have been proposed to either replace or supplement gluten-free diet therapy. In the past, non-dietary forms of treatment were used (e.g., corticosteroids) by some clinicians, often to supplement a gluten-free diet in patients that appeared to be poorly responsive to a gluten-free diet. Some of new and novel non-dietary measures have already advanced to a clinical trial phase. There are still some difficulties even if initial studies suggest a particularly exciting and novel form of non-dietary treatment. In particular, precise monitoring of the response to these agents will become critical. Symptom or laboratory improvement may be important, but it will be critical to ensure that ongoing inflammatory change and mucosal injury are not present. Therapeutic trials will be made more difficult because there is already an effective treatment regimen. PMID:24199026

  12. Celiac disease prevalence in epileptic children from Serbia.

    PubMed

    Djurić, Zlatko; Nagorni, Aleksandar; Jocić-Jakubi, Bosa; Dimić, Milena; Novak, Martin; Milićević, Radovan; Radenković, Goran

    2012-01-01

    Celiac disease (CD) is a genetically determined autoimmune enteropathy, induced by gluten ingestion. To date, different prevalences of CD in children with epilepsy have been reported. The aim of this study was to determine CD prevalence in our patients with epilepsy, using anti-tissue transglutaminase (tTG) antibodies as a screening test. One hundred twenty-five children (72 girls, 53 boys; age range: 2-18 years, mean age: 10.51 +/- 3.53) with idiopathic epilepsy from South East Serbia were tested for immunoglobulin (IgA) tTG antibodies. All positive patients were offered endoscopic small bowel biopsy. Biopsies were examined histopathologically in order to confirm the CD diagnosis. The control group consisted of 150 healthy children. Three patients with epilepsy were positive for IgA tTG antibodies. In all of them, small bowel biopsy was performed, and only one was proven to have CD by histopathology (Marsh IIIa grade). The prevalence of biopsy-proven CD in children with epilepsy was not significantly higher in the study group compared to controls (0.8% vs.0.6%, p > 0.05). The results of this study indicate that children with idiopathic epilepsy from our region should not be routinely tested for CD. PMID:23094534

  13. Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease.

    PubMed

    Rey, Martial; Yang, Menglin; Lee, Linda; Zhang, Ye; Sheff, Joey G; Sensen, Christoph W; Mrazek, Hynek; Halada, Petr; Man, Petr; McCarville, Justin L; Verdu, Elena F; Schriemer, David C

    2016-01-01

    Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates, and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1. PMID:27481162

  14. Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease

    PubMed Central

    Rey, Martial; Yang, Menglin; Lee, Linda; Zhang, Ye; Sheff, Joey G.; Sensen, Christoph W.; Mrazek, Hynek; Halada, Petr; Man, Petr; McCarville, Justin L; Verdu, Elena F.; Schriemer, David C.

    2016-01-01

    Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates, and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1. PMID:27481162

  15. Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM) Study Design: Approach to the Future of Personalized Prevention of Celiac Disease

    PubMed Central

    Leonard, Maureen M.; Camhi, Stephanie; Huedo-Medina, Tania B.; Fasano, Alessio

    2015-01-01

    In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD). Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease. PMID:26569299

  16. Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM) Study Design: Approach to the Future of Personalized Prevention of Celiac Disease.

    PubMed

    Leonard, Maureen M; Camhi, Stephanie; Huedo-Medina, Tania B; Fasano, Alessio

    2015-11-11

    In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD). Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.

  17. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    PubMed Central

    Scanlon, Samantha A; Murray, Joseph A

    2011-01-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions. PMID:22235174

  18. Celiac disease screening in southern and East Asia.

    PubMed

    Makharia, Govind K

    2015-01-01

    Until 1970s, celiac disease (CD) was considered to be an uncommon disease except in Western Europe. The global epidemiology of CD continues to evolve with improvement in the diagnostic tests, simplification of the diagnostic criteria and increase in awareness about the disease. The Asian region is currently at the crossroads of the frontier of knowledge and awareness of CD. In many Asian nations, CD is still considered to be either nonexistent or very rare. A notable exception is India, where CD has been well recognized, especially in the northern part, and 2 population-based studies have revealed a prevalence of 0.3-1.04%. Initial reports from Malaysia, China, Japan and Singapore suggest the existence of CD in these countries. Furthermore, a meta-analysis of the predisposing factors predicts a high probability of occurrence of CD in fair numbers in China. There are no formal reports on CD from Malaysia, Indonesia, Korea, Taiwan and many other nations in this region. With the impending CD epidemic in Asia, there are many challenges. Some of the efforts which are required include determination of prevalence of CD across the region, spreading of awareness among physicians and patients, training of dieticians for proper counseling and supervision of patients, creation of gluten-free food infrastructure in the food supply and creation of patient advocacy organizations. Although the absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years/decades. It is thus appropriate that the medical community across Asia define the extent of the problem and get prepared to handle the impending CD epidemic.

  19. Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability?

    PubMed

    Sezer, Taner; Balcı, Oya; Özçay, Figen; Bayraktar, Nilufer; Alehan, Füsun

    2016-03-01

    To determine the prevalence of celiac disease in children and adolescents with nonsyndromic intellectual disability, we investigated serum levels of tissue transglutaminase antibody and total IgA from 232 children with nonsyndromic intellectual disability and in a healthy control group of 239 children. Study participants who were positive for tissue transglutaminase antibody underwent a duodenal biopsy. A total of 3 patients in the nonsyndromic intellectual disability group (5.45%) and 1 in the control group (0.41%) had positive serum tissue transglutaminase antibody (P > .05). Duodenal biopsy confirmed celiac disease in only 1 patient who had nonsyndromic intellectual disability. In this present study, children with nonsyndromic intellectual disability did not exhibit a higher celiac disease prevalence rate compared with healthy controls. Therefore, we suggest that screening test for celiac disease should not be necessary as a part of the management of mild and moderate nonsyndromic intellectual disability. However, cases of severe nonsyndromic intellectual disability could be examined for celiac disease. PMID:26078418

  20. Frequency of Celiac Disease in Patients With Increased Intestinal Gas (Flatulence).

    PubMed

    Masoodi, Mohsen; Mokhtare, Marjan; Agah, Shahram; Sina, Mohammad; Soltani-Kermanshahi, Mojtaba

    2015-10-26

    Excessive flatulence which impairs social performance in patients is one of the common reasons for referrals to gastroenterology clinics. Celiac Disease is a rare but important cause of increased intestinal gas (bloating) and if not diagnosed, patients face complications such as malabsorption, anemia, osteoporosis and even intestinal lymphoma. This study aimed to determine the frequency of Celiac Disease in patients with excessive flatulence.One hundred and fifty patients with a chief complaint of experiencing flatulence more than 15 times a day and lasting for three months were referred to the gastroenterology clinic of Rasoul-e-Akram Teaching Hospital. Serological tests for Celiac Disease, Anti TTG Ab (IgA-IgG) were requested and the patients with positive tests underwent upper GI endoscopy. Biopsies of the second part of the duodenum were then sent to the laboratory.From one hundred and thirty patients who completed the study, 92 (70.7%) were female. Mean age of the patients was 32 ± 13 years. Anti TTG Ab was found in 5 patients (3.85%). Only 2 patients (1.5%) had a documented positive pathology for Celiac Disease.According to the results of this study and other studies, we conclude that Celiac Disease is an uncommon etiology for excessive flatulence but it is of importance to investigate it in excessive flatulence patients.

  1. Enteroscopy and radiology for the management of celiac disease complications: Time for a pragmatic roadmap.

    PubMed

    Branchi, Federica; Locatelli, Martina; Tomba, Carolina; Conte, Dario; Ferretti, Francesca; Elli, Luca

    2016-06-01

    Celiac disease is the most common autoimmune enteropathy in Western countries, and is usually associated with a good response to the gluten free diet and an excellent prognosis. However, a minority of patients develop complications of the disease, such as refractory celiac disease, ulcerative jejunoileitis and neoplastic complications such as adenocarcinoma of the small bowel and enteropathy associated T cell lymphoma. Neoplastic complications described in association with celiac disease have a high mortality rate, due to their aggressive behavior and to the usual advanced stage at the time of diagnosis. In recent years, the detection of small bowel lesions has dramatically improved thank to the availability of highly performing radiologic and endoscopic techniques. The diagnostic delay of malignant complications in patients with celiac disease may be improved by establishing a pragmatic flowchart for the identification and follow up of "at risk" patients. We performed a comprehensive review of the articles published on this issue in order to promote a roadmap to be applied when facing with celiac patients with suspected small bowel complications.

  2. Gene Expression Profile of Peripheral Blood Monocytes: A Step towards the Molecular Diagnosis of Celiac Disease?

    PubMed Central

    Cielo, Donatella; Morelli, Marinita; Gambino, Giuseppina; Zanzi, Delia; Strisciuglio, Caterina; Sperandeo, Maria Pia; Greco, Luigi; Auricchio, Renata

    2013-01-01

    Aim Celiac disease (CD) is a multifactorial autoimmune disease induced by ingestion of gluten in genetically predisposed individuals. Despite technological progress, the diagnosis of CD is still based on duodenal biopsy as it was 50 years ago. In this study we analysed the expression of CD-associated genes in small bowel biopsies of patients and controls in order to explore the multivariate pathway of the expression profile of CD patients. Then, using multivariant discriminant analysis, we evaluated whether the expression profiles of these genes in peripheral blood monocytes (PBMs) differed between patients and controls. Participants Thirty-seven patients with active and 11 with treated CD, 40 healthy controls and 9 disease controls (Crohn’s disease patients) were enrolled. Results Several genes were differentially expressed in CD patients versus controls, but the analysis of each single gene did not provided a comprehensive picture. A multivariate discriminant analysis showed that the expression of 5 genes in intestinal mucosa accounted for 93% of the difference between CD patients and controls. We then applied the same approach to PBMs, on a training set of 20 samples. The discriminant equation obtained was validated on a testing cohort of 10 additional cases and controls, and we obtained a correct classification of all CD cases and of 91% of the control samples. We applied this equation to treated CD patients and to disease controls and obtained a discrimination of 100%. Conclusions The combined expression of 4 genes allows one to discriminate between CD patients and controls, and between CD patients on a gluten-free diet and disease controls. Our results contribute to the understanding of the complex interactions among CD-associated genes, and they may represent a starting point for the development of a molecular diagnosis of celiac disease. PMID:24069342

  3. Type 1 Diabetes and Celiac Disease: Clinical Overlap and New Insights into Disease Pathogenesis

    PubMed Central

    Cohn, Aaron; Sofia, M. Anthony; Kupfer, Sonia S.

    2014-01-01

    Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with clinical and pathogenic overlap. The mean prevalence of CD in patients with T1D is about 8%. Classic intestinal symptoms of CD may not be present in T1D leading to the recommendation for active case finding in this higher risk group. Screening is done with sensitive and specific serologies including tissue transglutaminase (tTG) IgA and deaminated gliadin peptide (DGP) IgA and IgG. Positive serologies are confirmed by the presence of villous atrophy and increased intraepithelial lymphocytes on duodenal biopsy. A strict gluten free diet is recommended, although this can pose challenges for T1D patients who already have dietary restrictions. In aggregate, it appears as if the gluten free diet may help T1D management. T1D and CD have overlapping genetic and environmental risk factors. Among these, non-HLA genetic factors and the gut microbiome are among recent developments that will be discussed in this review. PMID:24952108

  4. Celiac disease in children: is it a problem in Kuwait?

    PubMed Central

    Al-Qabandi, Wafa’a; Buhamrah, Eman; Al-Abdulrazzaq, Dalia; Hamadi, Khaled; Al Refaee, Fawaz

    2015-01-01

    Background Celiac disease (CD) is a chronic inflammatory disease of the small intestine triggered by gluten ingestion. The objective of this study is to describe our experience with CD children in Kuwait. Methods The records of children with CD seen in the pediatric gastroenterology unit between February 1998 and December 2010 were retrospectively reviewed. Patients were referred because of symptoms or positive CD antibody screening of a high-risk group (type 1 diabetes and Down syndrome). Results Forty-seven patients were diagnosed: 53% were symptomatic and 47% were identified by screening. The median age at diagnosis was 66 (range 7–189) months. All cases were biopsy-proven except one. The symptomatic patients were significantly younger than those identified following screening (P<0.004). In the whole group, 66% were females and 77% were Kuwaitis; 9% had a positive family history of CD. The estimated cumulative incidence was 6.9/105. The median duration of symptoms before diagnosis was 8.5 (range 2–54) months. Failure to thrive was the most common presenting complaint (72%) followed by diarrhea (64%) and abdominal distension (56%). Atypical manifestations were seen in 60% of patients. Underweight and short stature were confirmed in 19% and 17% of patients, respectively. Overweight and obesity were detected in 14% and 6%, respectively. CD serology was based on a combination of antiendomysial and antigliadin antibodies. The median follow up was 24 (range 12–144) months. All patients were commenced on a gluten free diet, but good compliance was only achieved in 78%. Conclusion The low frequency of childhood CD in Kuwait could probably be attributed to either an underestimation of the atypical presentations or failure of proper screening. Also, adherence to a gluten free diet is a major problem in our population. PMID:25565879

  5. Sensorineural hearing loss and celiac disease: A coincidental finding

    PubMed Central

    Volta, Umberto; Ferri, Gian Gaetano; De Giorgio, Roberto; Fabbri, Angela; Parisi, Claudia; Sciajno, Laura; Castellari, Alessandra; Fiorini, Erica; Piscaglia, Maria; Barbara, Giovanni; Granito, Alessandro; Pirodda, Antonio

    2009-01-01

    BACKGROUND Celiac disease (CD) can be associated with a variety of extraintestinal manifestations, including neurological diseases. A new neurological correlation has been found between CD and sensorineural hearing loss (SNHL). OBJECTIVE To verify the association between SNHL and CD, and to establish whether the neurological hearing impairment in CD is related to nonorgan-specific and antineuronal antibodies, as well as the presence of autoimmune disorders. METHODS A sample of 59 consecutive biopsy- and serologically proven CD patients were studied. Among CD patients, 11 were newly diagnosed and 48 were on a gluten-free diet. Hearing function was assessed by audiometric analysis in all CD patients as well as in 59 age- and sex-matched controls. Patients were tested for a panel of immune markers including nonorgan-specific autoantibodies and antineuronal antibodies. RESULTS SNHL was detected in five CD patients (8.5%) and in two controls (3.4%). In one patient, the SNHL was bilateral, whereas the remaining four had a monolateral impairment. The prevalence of SNHL was not significantly different between CD patients and controls. At least one of the antibodies tested for was positive in two of the five CD patients with SNHL and in 12 of the 54 CD patients without SNHL. Antineuronal antibodies to central nervous system antigens were consistently negative in the five CD patients with SNHL. Only one of the five CD patients with SNHL had Hashimoto thyroiditis. CONCLUSIONS SNHL and CD occur coincidentally. Hearing function should be assessed only in CD patients with clinical signs of hearing deficiency. PMID:19668795

  6. Evidence Against Routine Testing of Patients with Functional Gastrointestinal Disorders for Celiac Disease: A Population-based Study

    PubMed Central

    Choung, Rok Seon; Rubio-Tapia, Alberto; Lahr, Brian D.; Kyle, Robert A.; Camilleri, Michael J.; Locke, G. Richard; Talley, Nicholas J.; Murray, Joseph A.

    2015-01-01

    Background & Aims Celiac disease has been linked to irritable bowel syndrome (IBS)-like symptoms in outpatient clinics. Guidelines recommend that all patients with IBS-like symptoms undergo serologic testing for celiac disease, but there is controversy over whether celiac disease is more prevalent in populations with IBS-like symptoms. We aimed to determine whether positive results from serologic tests for celiac disease are associated with IBS and other functional gastrointestinal disorders (FGIDs) in a large US White population. Methods Validated, self-report bowel disease questionnaires (BDQs) were sent to randomly selected cohorts of Olmsted County, Minnesota, residents. In separate protocols, serum samples were collected from more than 47,000 Olmsted County residents without a prior diagnosis of celiac disease; we performed serologic tests for celiac disease on stored serum samples from residents who completed the BDQ. Logistic regression was used to test for the association between serologic markers of celiac disease (positive vs negative) and individual FGIDs. Results A total of 3202 subjects completed the BDQ and had serum available for testing. IBS was identified in 13.6% of these subjects (95% confidence interval [CI], 12.4%–14.8%), and any gastrointestinal symptom occurred in 55.2% (95% CI, 53.5%−56.9%). The prevalence of celiac disease by based on serologic markers was 1.0% (95% CI, 0.7%–1.4%). IBS was less prevalent in patients with celiac disease (3%) than patients without celiac disease (14%), though the difference was not statistically significant (odds ratio=0.2; 95% CI, 0.03−1.5). Abdominal pain, constipation, weight loss, and dyspepsia were the most frequent symptom groups in subjects who were seropositive for celiac disease, but none of the gastrointestinal symptoms or disorders was significantly associated with celiac disease serology. Conclusions Symptoms indicative of FGIDs and sero-positive celiac disease are relatively common in a

  7. Patient Perception of Treatment Burden is High in Celiac Disease Compared to Other Common Conditions

    PubMed Central

    Shah, Sveta; Akbari, Mona; Vanga, Rohini; Kelly, Ciaran P.; Hansen, Joshua; Theethira, Thimmaiah; Tariq, Sohaib; Dennis, Melinda; Leffler, Daniel A.

    2014-01-01

    Introduction The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of celiac disease, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares to other medical treatments, and there are limited data on the socio-economic factors influencing treatment adherence. In this study we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence. Methods A survey was mailed to participants with: CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hypertension (HTN), diabetes mellitus (DM), congestive heart failure (CHF), and end stage renal disease on dialysis (ESRD). Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific and overall health status. Results We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment. Discussion Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for celiac disease argues for the need for safe adjuvant treatment as well as interventions designed to lower the perceived burden of the GFD. PMID:24980880

  8. Body mass index is not a reliable tool in predicting celiac disease in children

    PubMed Central

    2014-01-01

    Background Untreated celiac disease is traditionally believed to be associated with malabsorption and underweight. However, studies describing body mass index (BMI) in individuals at the time of diagnosis have shown contradictory results. We investigated the differences in weight, height, and BMI in 12- year-old children with screening-detected celiac disease compared to their healthy peers. Methods In a population-based screening study of 12,632 12-year-old children, blood samples were analyzed for markers of celiac disease. Children with elevated markers were referred for a small bowel biopsy. Weight and height were measured in 239 out of 242 children with screening-detected celiac disease (57.3% girls) and in 12,227 children without celiac disease (48.5% girls). BMI was categorized according to the International Obesity Task Force. Age- and sex-specific cut-off points for underweight, normal weight, and overweight were used. Results Children with celiac disease weighed less and were shorter than their peers (median weight 45.2 kg, interquartile range (IQR) 40.2–52.2 kg vs. 47.0 kg, IQR 41.1–54.4 kg, respectively, p = 0.01; median height 156.5 cm, IQR 151.0–162.0 cm vs. 157.5 cm, IQR 152.0–163.0 cm, respectively, p = 0.04). In comparing those with celiac disease to their healthy peers, 4.2% vs. 5.2% were underweight, 82.0% vs. 72.8% were normal weight, and 13.8% vs. 21.9% were overweight, respectively. There was no association between being underweight and the risk of having undiagnosed celiac disease (Odds ratio (OR) 1.3, 95% CI 0.7–2.4), but the risk was significantly lower among overweight children (OR 0.56, 95% CI 0.4–0.8). Median BMI was slightly lower among the children with screening-detected celiac disease compared to their healthy peers (18.6 kg/m2, IQR 17.1–19.8 kg/m2 vs. 18.8 kg/m2, IQR 17.2–21.1 kg/m2, respectively, p = 0.05), but most of the celiac disease cases had a normal BMI. Conclusions At a population level, children with celiac

  9. Symptomatic Secondary Selective IgM Immunodeficiency in Adult Man with Undiagnosed Celiac Disease

    PubMed Central

    Magen, Eli; Feldman, Viktor; Joseph, Mishal; Israel, Hadari

    2012-01-01

    Selective IgM immunodeficiency (SIgMID) is a heterogeneous disorder with no known genetic background and may occur as a primary or a secondary condition. Celiac disease has been reported in association with several humeral immunodeficiencies, including isolated severe selective IgA deficiency, panhypogammaglobulinemia, and isolated combined IgA and IgM deficiency. There are only few reported cases of pediatric and adult patients with SIgMID and celiac disease. In this paper, we describe an adult patient with a symptomatic secondary SIgMID associated with undiagnosed celiac disease, with a resolution of clinical symptoms of immunodeficiency and serum IgM normalization following a gluten-free diet. PMID:25374731

  10. Long-term consumption of oats in adult celiac disease patients.

    PubMed

    Kaukinen, Katri; Collin, Pekka; Huhtala, Heini; Mäki, Markku

    2013-11-01

    Many celiac disease patients tolerate oats, but limited data are available on its long-term consumption. This was evaluated in the present study, focusing on small-bowel mucosal histology and gastrointestinal symptoms in celiac adults maintaining a strict gluten-free diet with or without oats. Altogether 106 long-term treated celiac adults were enrolled for this cross-sectional follow-up study. Daily consumption of oats and fiber was assessed, and small-bowel mucosal morphology and densities of CD3+, αβ+ and γσ+ intraepithelial lymphocytes determined. Gastrointestinal symptoms were assessed by a validated Gastrointestinal Symptom Rating Scale questionnaire. Seventy (66%) out of the 106 treated celiac disease patients had consumed a median of 20 g of oats (range 1-100 g) per day for up to eight years; all consumed oat products bought from general stores. Daily intake and long-term consumption of oats did not result in small-bowel mucosal villous damage, inflammation, or gastrointestinal symptoms. Oat-consumers had a significantly higher daily intake of fiber than those who did not use oats. Two thirds of celiac disease patients preferred to use oats in their daily diet. Even long-term ingestion of oats had no harmful effects.

  11. Support for patients with celiac disease: A literature review

    PubMed Central

    Card, Tim; Ciclitira, Paul J; Swift, Gillian L; Nasr, Ikram; Sanders, David S; Ciacci, Carolina

    2015-01-01

    Background Celiac disease (CD) is a lifelong disorder. Patients are at increased risk of complications and comorbidity. Objectives We conducted a review of the literature on patient support and information in CD and aim to issue recommendations about patient information with regards to CD. Methods Data source: We searched PubMed for English-language articles published between 1900 and June 2014, containing terms related to costs, economics of CD, or education and CD. Study selection: Papers deemed relevant by any of the participating authors were included in the study. Data synthesis: No quantitative synthesis of data was performed. Instead we formulated a consensus view of the information that should be offered to all patients with CD. Results There are few randomized clinical trials examining the effect of patient support in CD. Patients and their families receive information from many sources. It is important that health care personnel guide the patient through the plethora of facts and comments on the Internet. An understanding of CD is likely to improve dietary adherence. Patients should be educated about current knowledge about risk factors for CD, as well as the increased risk of complications. Patients should also be advised to avoid other health hazards, such as smoking. Many patients are eager to learn about future non-dietary treatments of CD. This review also comments on novel therapies but it is important to stress that no such treatment is available at present. Conclusion Based on mostly observational data, we suggest that patient support and information should be an integral part of the management of CD, and is likely to affect the outcome of CD. PMID:25922674

  12. Increasing incidence of celiac disease in a North American population

    PubMed Central

    Ludvigsson, Jonas F.; Rubio-Tapia, Alberto; van Dyke, Carol T.; Melton, L. Joseph; Zinsmeister, Alan R.; Lahr, Brian D.; Murray, Joseph A.

    2013-01-01

    OBJECTIVES The prevalence of celiac disease (CD) varies greatly, potentially because of incomplete ascertainment of cases and small study samples with limited statistical power. Previous reports indicate that the incidence of CD is increasing. We examined the prevalence of CD in a well-defined US county. METHODS Population-based study in Olmsted County, Minnesota, US. Using the infrastructure of the Rochester Epidemiology Project, medical, histopathology, and CD serology records were used to identify all new cases of CD in Olmsted County since 2000. Age- and sex-specific and adjusted (to the US white 2000 population) incidence rates for CD were estimated. Clinical presentation at diagnosis was also assessed. RESULTS Between 2000 and 2010, 249 individuals (157 female or 63%, median age 37.9 years) were diagnosed with CD in Olmsted County. The overall age- and sex-adjusted incidence of CD in the study period was 17.4 (95% confidence interval [CI] = 15.2–19.6) per 100,000 person-years, increasing from 11.1 (95% CI=6.8–15.5) in 2000–2001 to 17.3 (95% CI=13.3–21.3) in 2008–2010. The temporal trend in incidence rates was modeled as a two-slope pattern, with the incidence leveling off after 2004. Based on the two classic CD symptoms of diarrhea and weight loss, the relative frequency of classical CD among incident cases decreased over time between 2000 and 2010 (p=0.044). CONCLUSION The incidence of CD has continued to increase in the past decade in a North American population. PMID:23511460

  13. Abnormal Skeletal Strength and Microarchitecture in Women With Celiac Disease

    PubMed Central

    Rogers, Halley; Leib, Alexa; McMahon, Donald J.; Young, Polly; Nishiyama, Kyle; Guo, X. Edward; Lewis, Suzanne; Green, Peter H.; Shane, Elizabeth

    2015-01-01

    Context: Osteoporosis is often a presenting sign of celiac disease (CD). Whether skeletal fragility in CD is associated with microarchitectural abnormalities is not known. Objective: The objective of the study was to evaluate microarchitecture and biomechanical properties of bone in CD. Design: This was a case-control study. Setting: The study was conducted at a university hospital outpatient facility. Patients: Patients included premenopausal women with newly diagnosed CD (n = 33) and healthy controls (n = 33). Main Outcome Measures: Areal bone mineral density by dual-energy x-ray absorptiometry was measured as was trabecular and cortical volumetric bone mineral density (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia. Whole-bone stiffness estimated by finite element analysis. PTH, 25-hydroxyvitamin D, and bone turnover markers were also measured. Results: Groups had similar age, race, and body mass index. Both groups had sufficient 25-hydroxyvitamin D and normal calcium and PTH. Areal bone mineral density was lower in CD. By high-resolution peripheral computed tomography, CD had lower trabecular vBMD, fewer, more widely, and irregularly spaced trabeculae at both the radius and tibia (8%–33%). At the tibia, they also had lower total density (8%) and thinner cortices (10%). Whole-bone stiffness and failure load were lower (11%–21%) in CD at both sites. Biomechanical deficits were associated with trabecular abnormalities. Conclusions: Women with CD had abnormal vBMD and microarchitecture at both the radius and tibia. Trabecular bone was preferentially affected. These deficits were associated with lower estimates of skeletal strength. These findings suggest a potential structural mechanism for skeletal fragility in CD and support further research into the pathogenesis of fracture in this population. PMID:25867815

  14. Humoral Immunity Links Candida albicans Infection and Celiac Disease

    PubMed Central

    Fradin, Chantal; Salleron, Julia; Damiens, Sébastien; Moragues, Maria Dolores; Souplet, Vianney; Jouault, Thierry; Robert, Raymond; Dubucquoi, Sylvain; Sendid, Boualem; Colombel, Jean Fréderic; Poulain, Daniel

    2015-01-01

    Objective The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI. Methods Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC). IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1. Results CI and CeD patients had higher levels of anti-Hwp1 (p=0.0005 and p=0.004) and anti-gliadin (p=0.002 and p=0.0009) antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p=0.0001 and p=0.0039). During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by γIII gliadin peptides. Conclusions Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals. PMID:25793717

  15. Assessment of Aortic Elasticity in Patients with Celiac Disease

    PubMed Central

    Çekin, Ayhan Hilmi; Arslan, Şakir; Çağırcı, Göksel; Küçükseymen, Selçuk; Çay, Serkan; Harmandar, Ferda Akbay; Yeşil, Bayram

    2016-01-01

    Background and Objectives Celiac disease (CD) is a chronic autoimmune disorder induced by dietary gluten intake by individuals who are genetically sensitive. Many studies report an increased risk of cardiovascular diseases in such patients. The aim of this study is to assess aortic elasticity properties in patients with CD that may be associated with an increased risk of cardiovascular disease. Subjects and Methods Eighty-one patients diagnosed with CD by antibody test and biopsy and 63 healthy volunteers were included in this prospective study. Electrocardiographic and echocardiographic examinations were performed. Results The CD group did not have any differences in the conventional echocardiographic parameters compared to the healthy individuals. However, patients in the CD group had an increased aortic stiffness beta index (4.3±2.3 vs. 3.6±1.6, p=0.010), increased pressure strain elastic modulus (33.6±17.0 kPa vs. 28.5±16.7 kPa, p=0.037), decreased aortic distensibility (7.0±3.0×10-6 cm2/dyn vs. 8.2±3.6×10-6 cm2/dyn, p=0.037), and similar aortic strain (17.9±7.7 vs. 16.0±5.5, p=0.070) compared to the control group. Patients with CD were found to have an elevated neutrophil/lymphocyte ratio compared to the control group (2.54±0.63 vs. 2.24±0.63, p=0.012). However, gluten-free diet and neutrophil/lymphocyte ratio were not found to be associated with aortic elasticity. Conclusion Patients with CD had increased aortic stiffness and decreased aortic distensibility. Gluten-free diet enabled the patients with CD to have a reduction in the inflammatory parameters whereas the absence of a significant difference in the elastic properties of the aorta may suggest that the risk of cardiovascular disease persists in this patient group despite a gluten-free diet. PMID:27014355

  16. Quantification of peptides causing celiac disease in historical and modern hard red spring wheat cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Celiac disease (CD) is prevalent in 0.5 to 1.26% of adolescents and adults. The disease develops in genetically susceptible individuals as a result of ingestion of gluten forming proteins found in cereals such as, wheat (Triticum aestivum L.), rye (Secale cereale L.) and barley (Hordeum sativum L.)...

  17. [Bone mineral density in patients with celiac disease and medical treatment of the disorder].

    PubMed

    Albulova, E A; Drozdov, V N; Parfenov, A I

    2011-01-01

    The article presents the results of a bone mineral density study in patients with glutensensitive celiac disease. Was discussed problem of malabsorption syndrome with clinical and pathogenetic point of view, which can lead to bone loss due to malabsorption of calcium and vitamin D for celiac disease. Also was take into account the effect of inflammatory cytokines and hormones on calcium regulating processes of bone remodeling. The role of adherence to a gluten-free diet in the formation of bone loss. The article is illustrated with three tables, one figure and two schedules. PMID:21695949

  18. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    PubMed

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  19. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population

    PubMed Central

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  20. Bone Mass and Mineral Metabolism Alterations in Adult Celiac Disease: Pathophysiology and Clinical Approach

    PubMed Central

    Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto

    2013-01-01

    Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition. PMID:24284619

  1. Celiac disease in Tunisian children: a second screening study using a "new generation" rapid test.

    PubMed

    Hariz, Mongi Ben; Laadhar, Lilia; Kallel-Sellami, Maryam; Siala, Nadia; Bouraoui, Saadia; Bouziri, Sonia; Borgi, Abdelhafidh; Karouia, Faouzia; Maherzi, Ahmed; Makni, Sondès

    2013-01-01

    This work aims to estimate celiac disease prevalence in school-children in the island of Djerba and assess rapid method feasibility for screening. We screened 2064 schoolchildren by a rapid method to detect IgA anti-tissue transglutaminase and IgA deficiency. Children with positive results were tested for IgA anti-transglutaminase and anti-endomysium by conventional tests. In positive children, intestinal biopsy was performed. IgA deficiency suspected by rapid method was confirmed by nephelometry. In these cases IgG anti-endomysium was performed. Rapid test was positive in 7 children; conventional serology was positive in all and 6 of them accepted the biopsy. Total villous atrophy was observed in 5 while intestinal mucosa was normal in one. Among children with positive serology, 3 had silent form, 1 chronic diarrhea, one growth failure and 2 had borderline growth. IgA deficiency was suspected in 13 cases and was confirmed in 11 children tested. Prevalence of celiac disease was 0.24-0.34% and that of IgA deficiency 0.5-0.6%. This screening study confirms that celiac disease is relatively common in schoolchildren in Tunisia. It confirms also that even those with symptoms typical for celiac disease escape diagnosis. Rapid test is better accepted by parents and children than test requiring a venous blood sample. PMID:23883201

  2. Celiac disease in T1DM—the need to look long term

    PubMed Central

    Rewers, Marian; Eisenbarth, George S.

    2012-01-01

    Does untreated celiac disease associated with type 1 diabetes mellitus worsen microvascular outcomes? Previous studies have concluded that a gluten-free diet offers no major benefit for glycemic control, whereas Leeds and colleagues provide preliminary data to the contrary. The question awaits a long-term prospective study or a clinical trial. PMID:22064502

  3. A Preliminary Investigation of ADHD Symptoms in Persons with Celiac Disease

    ERIC Educational Resources Information Center

    Niederhofer, Helmut; Pittschieler, Klaus

    2006-01-01

    Objective: Several studies report a possible association of celiac disease (CD) with psychiatric and psychological disturbances, such as ADHD. Method: The authors assess 132 participants from 3 to 57 years of age (M = 19.3 years) affected by CD for the possibility of an associated ADHD-like symptomatology, using the Conner Scale Hypescheme, a…

  4. Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Celiac disease is an immune-mediated enteropathy that is generally understood to be triggered by the ingestion of gluten proteins of wheat and related cereals. The skin manifestation of the condition is known as dermatitis herpetiformis. Antibody response to native and deamidated seque...

  5. Implementation of a polling protocol for predicting celiac disease in videocapsule analysis

    PubMed Central

    Ciaccio, Edward J; Tennyson, Christina A; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2013-01-01

    AIM: To investigate the presence of small intestinal villous atrophy in celiac disease patients from quantitative analysis of videocapsule image sequences. METHODS: Nine celiac patient data with biopsy-proven villous atrophy and seven control patient data lacking villous atrophy were used for analysis. Celiacs had biopsy-proven disease with scores of Marsh II-IIIC except in the case of one hemophiliac patient. At four small intestinal levels (duodenal bulb, distal duodenum, jejunum, and ileum), video clips of length 200 frames (100 s) were analyzed. Twenty-four measurements were used for image characterization. These measurements were determined by quantitatively processing the videocapsule images via techniques for texture analysis, motility estimation, volumetric reconstruction using shape-from-shading principles, and image transformation. Each automated measurement method, or automaton, was polled as to whether or not villous atrophy was present in the small intestine, indicating celiac disease. Each automaton’s vote was determined based upon an optimized parameter threshold level, with the threshold levels being determined from prior data. A prediction of villous atrophy was made if it received the majority of votes (≥ 13), while no prediction was made for tie votes (12-12). Thus each set of images was classified as being from either a celiac disease patient or from a control patient. RESULTS: Separated by intestinal level, the overall sensitivity of automata polling for predicting villous atrophy and hence celiac disease was 83.9%, while the specificity was 92.9%, and the overall accuracy of automata-based polling was 88.1%. The method of image transformation yielded the highest sensitivity at 93.8%, while the method of texture analysis using subbands had the highest specificity at 76.0%. Similar results of prediction were observed at all four small intestinal locations, but there were more tie votes at location 4 (ileum). Incorrect prediction which

  6. Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic control

    PubMed Central

    Scaramuzza, Andrea E; Mantegazza, Cecilia; Bosetti, Alessandra; Zuccotti, Gian Vincenzo

    2013-01-01

    Type 1 diabetes mellitus is associated with celiac disease, with a prevalence that varies between 0.6% and 16.4%, according to different studies. After a diagnosis of celiac disease is confirmed by small bowel biopsy, patients are advised to commence a gluten-free diet (GFD). This dietary restriction may be particularly difficult for the child with diabetes, but in Europe (and in Italy) many food stores have targeted this section of the market with better labeling of products and more availability of specific GFD products. Treatment with a GFD in symptomatic patients has been shown to improve the symptoms, signs and complications of celiac disease. However, the effects of a GFD on diabetic control are less well established. Initial reports of improved hypoglycemic control were based on children who were diagnosed with celiac disease associated with malabsorption, but there have subsequently been reports of improvement in patients with type 1 diabetes with subclinical celiac disease. There are other studies reporting no effect, improved control and an improvement of hypoglycemic episodes. Moreover, in this review we wish to focus on low glycemic index foods, often suggested in people with type 1 diabetes, since they might reduce postprandial glycemic excursion and enhance long-term glycemic control. In contrast, GFD may be rich in high glycemic index foods that can increase the risk of obesity, insulin resistance and cardiovascular disease, worsening the metabolic control of the child with diabetes. Hence, it is important to evaluate the impact of a GFD on metabolic control, growth and nutritional status in children with type 1 diabetes. PMID:23961323

  7. Perinatal Risk Factors for Development of Celiac Disease in Children Based on the Prospective Norwegian Mother and Child Cohort Study

    PubMed Central

    Emilsson, Louise; Magnus, Maria; Størdal, Ketil

    2014-01-01

    Background & Aims There have been inconsistent reports of pre- and perinatal factors that affect risk for development of celiac disease. We assessed the association of fetal growth, birth weight, and mode of delivery with development of celiac disease within the Norwegian Mother and Child (MoBa) cohort study. Methods The MoBa cohort contains pregnancy information on 95,200 women and data on their 114,500 children, collected in Norway from 1999 through 2008; it is linked to the Medical Birth Registry. Women and children with celiac disease were identified from the National Patient Register and from women's responses to MoBa questionnaires. We calculated odds ratios (ORs) for celiac disease using a multivariable logistic regression model, adjusting for maternal celiac disease, sex of children, and children's age (model 1); in a second model, we adjusted for age of gluten introduction and duration of breastfeeding (model 2). Results We identified 650 children with celiac disease and 107,828 controls in the MoBa database. We found no association between birth weight or height with celiac disease (born small for gestational age was not associated). Celiac disease was not associated with mode of delivery (Cesarean section, model 1: OR=0.84; 95% confidence interval [CI], 0.65–1.09 and model 2: OR=0.83; 95% CI, 0.63−1.09). Maternal celiac disease, adjusted for age and sex of the children (OR=12.45; 95% CI, 8.29−18.71) and type 1 diabetes (model I: OR=2.58; 95% CI, 1.19−5.53 and model 2: OR=2.61; 95% CI, 1.14−5.98) were associated with development of celiac disease in children, whereas maternal type 2 diabetes and gestational diabetes were not. Conclusion Based on analysis of the Norwegian MoBa cohort, development of celiac disease in children is significantly associated with sex of the child, maternal celiac disease and type 1 diabetes, but not with intrauterine growth. PMID:25459557

  8. Profound Reversible Hypogammaglobulinemia Caused by Celiac Disease in the Absence of Protein Losing Enteropathy.

    PubMed

    Ameratunga, Rohan; Barker, Russell William; Steele, Richard Henderson; Deo, Maneka; Woon, See-Tarn; Yeong, Mee Ling; Koopmans, Wikke

    2015-08-01

    When patients with hypogammaglobulinemia are encountered, a vigorous search should be undertaken for secondary treatable causes. Here we describe the first case of a patient with severe asymptomatic hypogammaglobulinemia where the underlying cause was undiagnosed celiac disease. A strict gluten free diet resulted in resolution of her mild long-standing abdominal symptoms and correction of her hypogammaglobulinemia. There was corresponding improvement in her duodenal histology and normalisation of her celiac serology. Protein losing enteropathy was unlikely to have been the mechanism of her profound hypogammaglobulinemia, as her albumin was within the normal range and she had a normal fecal alpha 1 antitrypsin level. Application of the Ameratunga et al. (2013) diagnostic criteria was helpful in confirming this patient did not have Common Variable Immunodeficiency Disorder (CVID). Celiac disease must now be considered in the differential diagnosis of severe hypogammaglobulinemia. There should be a low threshold for undertaking celiac serology in patients with hypogammaglobulinemia, even if they have minimal symptoms attributable to gut disease.

  9. Effectiveness of antigliadin antibodies as a screening test for celiac disease in children

    PubMed Central

    Chartrand, L J; Agulnik, J; Vanounou, T; Russo, P A; Baehler, P; Seidman, E G

    1997-01-01

    OBJECTIVE: To test the effectiveness of serologic antigliadin antibody (AGA) testing in predicting celiac disease in children. DESIGN: Prospective clinical assessment. SETTING: Hôpital Sainte-Justine, montreal. PATIENTS: A total of 176 children with possible celiac disease who were referred for duodenal biopsy between January 1992 and June 1995. OUTCOME MEASURES: IgA and IgG AGA titres, as determined by enzyme-linked immunosorbent assay (ELISA); duodenal biopsy; clinical outcome on a gluten-free diet. RESULTS: Of the 176 children 30 were found to have celiac disease according to the criteria of the European Society of Pediatric Gastroenterology and Nutrition (ESPGAN). The sensitivity and specificity of the IgA AGA titre, as well as its positive and negative predictive values, were 80%, 92%, 67% and 96% respectively; the corresponding values for the IgG AGA titre were 83%, 79%, 45% and 96%. The respective values for IgA and IgG AGA titres combined were 93%, 71%, 43% and 98%. Only 2 of the 30 patients with celiac disease had false-negative results for both IgA and IgG AGA titres. The IgA and IgG AGA titres decreased significantly (p < 0.005) in all 11 patients after being on a gluten-free diet for at least 10 months and reached normal values in 8. CONCLUSION: AGA screening for celiac disease permits better selection of patients for duodenal biopsy and adds specificity to the histologic diagnosis. Such screening cannot replace intestinal biopsy, which remains the gold standard for diagnosis. PMID:9294391

  10. Neuromyelitis optica-IgG+ optic neuritis associated with celiac disease and dysgammaglobulinemia: a role for tacrolimus?

    PubMed

    Meyts, Isabelle; Jansen, Katrien; Renard, Marleen; Bossuyt, Xavier; Roelens, Filip; Régal, Luc; Lagae, Lieven; Buyse, Gunnar

    2011-05-01

    We present a pediatric case of recurrent optic neuritis, celiac disease, partial IgA and IgG3 deficiency in the context of anti-aquaporin-4 auto-immunity and familial IgA deficiency with celiac disease. Treatment with tacrolimus was successful in preventing disease relapses. This case stresses the relevance of central nervous system anti-aquaporin-4 auto-immunity in a broader context of immune dysregulation and neuro-immunology.

  11. Electrochemical magneto immunosensor for the detection of anti-TG2 antibody in celiac disease.

    PubMed

    Kergaravat, Silvina V; Beltramino, Luis; Garnero, Nidia; Trotta, Liliana; Wagener, Marta; Isabel Pividori, Maria; Hernandez, Silvia R

    2013-10-15

    An electrochemical magneto immunosensor for the detection of anti-transglutaminase antibodies (ATG2) in celiac disease was developed. The immunological reaction is performed on magnetic beads (MBs) as a solid support in which the transglutaminase enzyme (TG2) is covalently immobilized (TG2-MB) and then ATG2 were revealed by an antibody labeled with peroxidase. The electrochemical response of the enzymatic reaction with o-phenilendiamine and H₂O₂ as substrates by square wave voltammetry was correlated with the ATG2. Graphite-epoxi composite cylindrical electrodes and screen printed electrodes were used as transducers in the immunosensor. A total number of 29 sera from clinically confirmed cases of celiac disease and 19 negative control sera were tested by the electrochemical magneto immunosensor. The data were submitted to the receiver-operating characteristic plot (ROC) analysis which indicated that 16.95 units was the most effective cut-off value (COV) to discriminate correctly between celiac and non-celiac patients. Using this point for prediction, sensitivity was found to be 100%, while specificity was 84%. PMID:23685317

  12. Electrochemical magneto immunosensor for the detection of anti-TG2 antibody in celiac disease.

    PubMed

    Kergaravat, Silvina V; Beltramino, Luis; Garnero, Nidia; Trotta, Liliana; Wagener, Marta; Isabel Pividori, Maria; Hernandez, Silvia R

    2013-10-15

    An electrochemical magneto immunosensor for the detection of anti-transglutaminase antibodies (ATG2) in celiac disease was developed. The immunological reaction is performed on magnetic beads (MBs) as a solid support in which the transglutaminase enzyme (TG2) is covalently immobilized (TG2-MB) and then ATG2 were revealed by an antibody labeled with peroxidase. The electrochemical response of the enzymatic reaction with o-phenilendiamine and H₂O₂ as substrates by square wave voltammetry was correlated with the ATG2. Graphite-epoxi composite cylindrical electrodes and screen printed electrodes were used as transducers in the immunosensor. A total number of 29 sera from clinically confirmed cases of celiac disease and 19 negative control sera were tested by the electrochemical magneto immunosensor. The data were submitted to the receiver-operating characteristic plot (ROC) analysis which indicated that 16.95 units was the most effective cut-off value (COV) to discriminate correctly between celiac and non-celiac patients. Using this point for prediction, sensitivity was found to be 100%, while specificity was 84%.

  13. Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer.

    PubMed

    van Beurden, Yvette H; van Gils, Tom; van Gils, Nienke A; Kassam, Zain; Mulder, Chris J J; Aparicio-Pagés, Nieves

    2016-09-01

    Treatment of refractory celiac disease type II (RCD II) and preventing the development of an enteropathy associated T-cell lymphoma in these patients is still difficult. In this case report, we describe a patient with RCD II who received fecal microbiota transfer as treatment for a recurrent Clostridium difficile infection, and remarkably showed a full recovery of duodenal villi and disappearance of celiac symptoms. This case suggests that altering the gut microbiota may hold promise in improving the clinical and histological consequences of celiac disease and/or RCD II. PMID:27689204

  14. Canadian Digestive Health Foundation Public Impact Series 4: Celiac disease in Canada. Incidence, prevalence, and direct and indirect economic impact

    PubMed Central

    Fedorak, Richard N; Switzer, Connie M; Bridges, Ron J

    2012-01-01

    The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning celiac disease. PMID:22720277

  15. 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

  16. 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

  17. [Chronic Duodenitis and Celiac Disease: a path between the nonspecific and the early stages of Marsh].

    PubMed

    Passera, Andrea Helena; Passera, Mario Luis; Higa, Antonio Luis; Nuñez, Maria; Armando, Lucas; Barzón, Silvia

    2015-01-01

    Given the advances in diagnosis for CD, some patients are detected with symptoms and signs of food intolerance, which have positive antibodies and autoantibodies for coeliac disease, whom present proximal bowel biopsies with chronic nonspecific duodenitis and are not associated with stages 0 and 1 Marsh. On the other hand, patients with bloating, abdominal pain, pondostatural delay, negative antibodies for CD, and chronic nonspecific duodenitis in whom removing cow's milk or gluten, the symptoms remit. There are also celiac patients with biopsies before diagnosis, with chronic nonspecific duodenitis. In this paper, we summarize three brothers with different degrees of chronic duodenitis, one with chronic nonspecific duodenitis, and two with histopathological sings of coeliac disease. It is an invitation to think that chronic nonspecific duodenitis in some patients may be an earlier manifestation of celiac disease.

  18. Bone and mineral metabolism in adult celiac disease

    SciTech Connect

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  19. Bones of contention: bone mineral density recovery in celiac disease--a systematic review.

    PubMed

    Grace-Farfaglia, Patricia

    2015-05-01

    Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.

  20. Cancer in first-degree relatives of people with celiac disease

    PubMed Central

    Emilsson, Louise; Murray, Joseph A.; Leffler, Daniel A.; Ludvigsson, Jonas F.

    2016-01-01

    Abstract Background: Celiac disease (CD) has been linked to cancer, especially lymphoproliferative malignancy (LPM). Earlier research has shown that first-degree relatives (FDRs) to individuals with CD are at increased risk of autoimmunity including CD, but data on their risk of cancer are scarce and contradictory. We aimed to assess whether Swedish FDRs to individuals with CD are at increased risk of cancer. Methods: Individuals with CD (identified through biopsy reports equal to Marsh grade III) were matched on sex, age, county, and calendar year with up to 5 control individuals. All FDRs (father, mother, sibling, offspring) of CD individuals (“celiac FDRs”: n = 109,391) and controls (n = 548,465) were identified through Swedish healthcare registries. Through Cox regression, we calculated hazard ratios (HRs) for cancer incidence (all cancer, breast cancer, gastrointestinal cancer, and LPM). Results: During follow-up, celiac FDRs experienced 10,750 unique cancers as opposed to 54,686 in-control FDRs. Celiac FDRs were at a slightly lower risk of any cancer (HR 0.97, 95% confidence interval [CI] 0.95–0.99), partially due to the lower risk of breast cancer (HR 0.92, 95% CI 0.87–0.98). The relative risks of LPM (HR 0.99, 95% CI 0.91–1.08) and gastrointestinal cancer (HR 0.98, 95%CI 0.93–1.03) were both close to 1. As opposed to earlier research, we found no excess risk of LPM in siblings to individuals with CD (HR 0.98, 95% CI 0.81–1.19). Conclusion: Celiac FDRs are not at increased risk of cancer, including LPM, arguing that shared genetics is unlikely to explain previous reports of an excess risk of LPM in patients with CD. PMID:27512889

  1. Onset of Celiac Disease after Treatment of Chronic Hepatitis C with Interferon Based Triple Therapy

    PubMed Central

    Singh, Amandeep; Zaeri, Nayere; Ho, Immanuel K.

    2015-01-01

    Background. Patients treated with interferon (IFN) based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disease (CD) as a result of triple therapy (interferon, ribavirin, and boceprevir) for chronic HCV. Case. 53-year-old Caucasian female with past medical history of IV drug abuse was referred for abnormal LFTs. Laboratory data showed HCV RNA of 4,515,392 IU/mL, HCV genotype 1a, with normal LFTs. She was treated with 4 weeks of pegylated interferon alfa-2a plus ribavirin, followed by triple therapy using boceprevir for a total of 28 weeks. Approximately 4 weeks after initiation of triple therapy patient developed loose nonbloody bowel movements and was also found to have anemia. Biopsies from first and second portions of the duodenum were consistent with CD. The patient was treated with a gluten-free diet. Her intestinal symptoms improved and the hemoglobin returned to normal. Conclusion. Chronic HCV patients being treated with interferon alfa can develop celiac disease during or after therapy. For patients with positive autoantibodies, all-oral-IFN-free regimens should be considered. Celiac disease should be considered in patients who develop CD-like symptoms while on and shortly after cessation of interferon alfa therapy. PMID:26664772

  2. 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.

  3. 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

  4. MICA∗078: A novel allele identified in a Moroccan individual affected by celiac disease.

    PubMed

    Piancatelli, Daniela; Oumhani, Khadija; Benelbarhdadi, Imane; Del Beato, Tiziana; Colanardi, Alessia; Sebastiani, Pierluigi; Tessitore, Alessandra; El Aouad, Rajae; Essaid, Abdellah

    2015-06-01

    A novel MICA allele, MICA(∗)078, has been identified during HLA/MICA high resolution typing of Moroccan patients with celiac disease. MICA(∗)078 shows an uncommon variation at a highly conserved nucleotide position (nt 493, G → A), resulting in one amino acid change at codon 142 (V → I) of MICA gene (compared to MICA(∗)002:01), located in the α2-domain, in which V142 is the common residue.

  5. Ratio of spleen diameter to red blood cell distribution width: a novel indicator for celiac disease.

    PubMed

    Balaban, Daniel Vasile; Popp, Alina; Lungu, Andrei Marian; Costache, Raluca Simona; Anca, Ioana Alina; Jinga, Mariana

    2015-04-01

    Celiac disease (CD) is currently considerably underdiagnosed, setting the need for developing tools to select patients with probability of CD, who warrant further testing. Red blood cell distribution width (RDW) has been shown in previous studies to be a sensitive predictor for CD, but it lacks specificity. Splenic hypotrophy is also noted frequently in celiac patients. Our aim was to evaluate if spleen diameter to RDW ratio can be used as an indicator for CD. We evaluated 15 newly diagnosed CD patients, 52 patients with inflammatory bowel disease, and 35 patients with irritable bowel syndrome (IBS). We evaluated the differences in spleen diameter, RDW, and their ratio among the four groups. Two-thirds of the CD patients had elevated RDW, compared to 9% in the IBS group. A small spleen was seen in 80% of the celiacs, compared to 21.9% in the ulcerative colitis group, 10% in the Crohn disease group, and 9% in the IBS group. A spleen diameter to RDW ratio under 6 had a sensitivity of 73.3% and specificity of 88.5% in predicting CD, with an AUROC of 0.737. Spleen diameter to RDW ratio is a simple, widely available score, which can be used to select adult patients with probability of CD. PMID:25881851

  6. Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

    PubMed Central

    2014-01-01

    While the antigenic specificity and pathogenic relevance of immunologic reactivity to gluten in celiac disease have been extensively researched, the immune response to nongluten proteins of wheat has not been characterized. We aimed to investigate the level and molecular specificity of antibody response to wheat nongluten proteins in celiac disease. Serum samples from patients and controls were screened for IgG and IgA antibody reactivity to a nongluten protein extract from the wheat cultivar Triticum aestivum Butte 86. Antibodies were further analyzed for reactivity to specific nongluten proteins by two-dimensional gel electrophoresis and immunoblotting. Immunoreactive molecules were identified by tandem mass spectrometry. Compared with healthy controls, patients exhibited significantly higher levels of antibody reactivity to nongluten proteins. The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins. Assessment of reactivity toward purified recombinant proteins further confirmed the presence of antibody response to specific antigens. The results demonstrate that, in addition to the well-recognized immune reaction to gluten, celiac disease is associated with a robust humoral response directed at a specific subset of the nongluten proteins of wheat. PMID:25329597

  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

    2014-03-01

    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. 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.

  9. Cardiovascular disease risk factor profiles in children with celiac disease on gluten-free diets

    PubMed Central

    Norsa, Lorenzo; Shamir, Raanan; Zevit, Noam; Verduci, Elvira; Hartman, Corina; Ghisleni, Diana; Riva, Enrica; Giovannini, Marcello

    2013-01-01

    AIM: To describe the cardiovascular disease (CVD) risk factors in a population of children with celiac disease (CD) on a gluten-free diet (GFD). METHODS: This cross-sectional multicenter study was performed at Schneider Children’s Medical Center of Israel (Petach Tiqva, Israel), and San Paolo Hospital (Milan, Italy). We enrolled 114 CD children in serologic remission, who were on a GFD for at least one year. At enrollment, anthropometric measurements, blood lipids and glucose were assessed, and compared to values at diagnosis. The homeostasis model assessment-estimated insulin resistance was calculated as a measure of insulin resistance. RESULTS: Three or more concomitant CVD risk factors [body mass index, waist circumference, low density lipoprotein (LDL) cholesterol, triglycerides, blood pressure and insulin resistance] were identified in 14% of CD subjects on a GFD. The most common CVD risk factors were high fasting triglycerides (34.8%), elevated blood pressure (29.4%), and high concentrations of calculated LDL cholesterol (24.1%). On a GFD, four children (3.5%) had insulin resistance. Fasting insulin and HOMA-IR were significantly higher in the Italian cohort compared to the Israeli cohort (P < 0.001). Children on a GFD had an increased prevalence of borderline LDL cholesterol (24%) when compared to values (10%) at diagnosis (P = 0.090). Trends towards increases in overweight (from 8.8% to 11.5%) and obesity (from 5.3% to 8.8%) were seen on a GFD. CONCLUSION: This report of insulin resistance and CVD risk factors in celiac children highlights the importance of CVD screening, and the need for dietary counseling targeting CVD prevention. PMID:24039358

  10. Pathological and Clinical Correlation between Celiac Disease and Helicobacter Pylori Infection; a Review of Controversial Reports.

    PubMed

    Rostami-Nejad, Mohammad; Javad Ehsani-Ardakani, Mohammad; Assadzadeh, Hamid; Shahbazkhani, Bijan; Ierardi, Enzo; Losurdo, Giuseppe; Zojaji, Homayon; Alizadeh, Amirhoshang Mohammad; Naderi, Nosratollah; Sadeghi, Amir; Zali, Mohammad Reza

    2016-04-01

    There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection. PMID:27252814

  11. Pathological and Clinical Correlation between Celiac Disease and Helicobacter Pylori Infection; a Review of Controversial Reports

    PubMed Central

    Rostami-Nejad, Mohammad; Javad Ehsani-Ardakani, Mohammad; Assadzadeh, Hamid; Shahbazkhani, Bijan; Ierardi, Enzo; Losurdo, Giuseppe; Zojaji, Homayon; Alizadeh, Amirhoshang Mohammad; Naderi, Nosratollah; Sadeghi, Amir; Zali, Mohammad Reza

    2016-01-01

    There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection. PMID:27252814

  12. Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations

    PubMed Central

    Caio, Giacomo; Giorgio, Roberto De; Venturi, Alessandro; Giancola, Fiorella; Latorre, Rocco; Boschetti, Elisa; Serra, Mauro; Ruggeri, Eugenio; Volta, Umberto

    2015-01-01

    Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P< 0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively. PMID:25926940

  13. The Relationship between Spontaneous Multi-Vessel Coronary Artery Dissection and Celiac Disease

    PubMed Central

    Çağırcı, Göksel; Üreyen, Çağın Mustafa; Kuş, Görkem; Küçükseymen, Selçuk; Arslan, Şakir

    2015-01-01

    Celiac disease (CD) is an immune-mediated enteropathy involving the small intestines. Genetic and environmental risk factors as well as autoimmunity have been linked to its etiology. Studies have shown that coronary artery disease, autoimmune myocarditis, arrhythmias and premature atherosclerosis are more prevalent in individuals with CD compared to individuals without the disease. In this case report a young male patient with CD presented with acute myocardial infarction with spontaneous coronary artery dissections of two vessels. To the best of our knowledge, this is the first case report of spontaneous multi-vessel coronary artery dissection in a patient with CD. PMID:26023313

  14. Suggestions for automatic quantitation of endoscopic image analysis to improve detection of small intestinal pathology in celiac disease patients.

    PubMed

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2015-10-01

    Although many groups have attempted to develop an automated computerized method to detect pathology of the small intestinal mucosa caused by celiac disease, the efforts have thus far failed. This is due in part to the occult presence of the disease. When pathological evidence of celiac disease exists in the small bowel it is visually often patchy and subtle. Due to presence of extraneous substances such as air bubbles and opaque fluids, the use of computerized automation methods have only been partially successful in detecting the hallmarks of the disease in the small intestine-villous atrophy, fissuring, and a mottled appearance. By using a variety of computerized techniques and assigning a weight or vote to each technique, it is possible to improve the detection of abnormal regions which are indicative of celiac disease, and of treatment progress in diagnosed patients. Herein a paradigm is suggested for improving the efficacy of automated methods for measuring celiac disease manifestation in the small intestinal mucosa. The suggestions are applicable to both standard and videocapsule endoscopic imaging, since both methods could potentially benefit from computerized quantitation to improve celiac disease diagnosis.

  15. Health-related quality of life is not impaired in children with undetected as well as diagnosed celiac disease: a large population based cross-sectional study

    PubMed Central

    2014-01-01

    Background Knowledge regarding the health-related quality of life (HRQoL) of children with celiac disease remains limited and inconclusive. We investigated the HRQoL of three groups of 12-year-olds with: i) undetected celiac disease ii) clinically diagnosed celiac disease, and iii) without celiac disease. Methods A school-based cross-sectional multicenter screening study invited 18 325 children, whereof 68% consented to participate. Participants provided a blood sample, which was later analyzed for anti-tissue-tranglutaminase antibodies, and alongside filled in a questionnaire. When anti-tissue-tranglutaminase antibodies were elevated, a small intestinal biopsy verified the screening-detected celiac disease diagnosis. Self-reported HRQoL was measured using Kidscreen, a generic 52 items instrument with proven reliability and validity. Scores were linearly transformed into a 0–100 scale with higher values indicating better HRQoL. Mean values with standard deviations (mean ± SD) were compared, and uni- and multivariate logistic regression models tested the odds of a low HRQoL among children with undetected or diagnosed celiac disease, respectively. Results Children with undetected celiac disease (n = 238) reported similar HRQoL as children without celiac disease (n = 12 037) (83.0 ± 11.0 vs. 82.5 ± 11.3, P = 0.51), and also similar HRQoL (82.2 ± 12.2, P = 0.28) to that of children with diagnosed celiac disease (n = 90), of whom 92% were adherent to treatment. Having undetected celiac disease did not increase the odds of low overall HRQoL, independent of sex, area of residence, study year and occurrence of gastrointestinal symptoms (adjusted odds ratio 0.77, 95% CI 0.54-1.10). Comparable results were seen for diagnosed celiac disease cases (adjusted odds ratio 1.11, 95% CI 0.67-1.85). Conclusion Children with undetected celiac disease reported comparable HRQoL as their peers with diagnosed celiac disease, and those without celiac disease

  16. Screening for celiac disease in the general population and in high-risk groups

    PubMed Central

    Card, Timothy R; Kaukinen, Katri; Bai, Julio; Zingone, Fabiana; Sanders, David S; Murray, Joseph A

    2015-01-01

    Background Celiac disease (CD) occurs in approximately 1% of the Western population. It is a lifelong disorder that is associated with impaired quality of life (QOL) and an excessive risk of comorbidity and death. Objectives To review the literature on screening for CD in relation to the current World Health Organization (WHO) criteria for mass screening. Methods We performed a PubMed search to identify indexed papers on CD screening with a publication date from 1900 until 1 June 2014. When we deemed an abstract relevant, we read the corresponding paper in detail. Results CD fulfills several WHO criteria for mass screening (high prevalence, available treatment and difficult clinical detection), but it has not yet been established that treatment of asymptomatic CD may reduce the excessive risk of severe complications, leading to higher QOL nor that it is cost-effective. Conclusions Current evidence is not sufficient to support mass screening for CD, but active case-finding may be appropriate, as we recognize that most patients with CD will still be missed by this strategy. Although proof of benefit is still lacking, screening for CD may be appropriate in high-risk groups. PMID:25922671

  17. 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

  18. Production of the Main Celiac Disease Autoantigen by Transient Expression in Nicotiana benthamiana

    PubMed Central

    Marín Viegas, Vanesa S.; Acevedo, Gonzalo R.; Bayardo, Mariela P.; Chirdo, Fernando G.; Petruccelli, Silvana

    2015-01-01

    Celiac Disease (CD) is a gluten sensitive enteropathy that remains widely undiagnosed and implementation of massive screening tests is needed to reduce the long term complications associated to untreated CD. The main CD autoantigen, human tissue transglutaminase (TG2), is a challenge for the different expression systems available since its cross-linking activity affects cellular processes. Plant-based transient expression systems can be an alternative for the production of this protein. In this work, a transient expression system for the production of human TG2 in Nicotiana benthamiana leaves was optimized and reactivity of plant-produced TG2 in CD screening test was evaluated. First, a subcellular targeting strategy was tested. Cytosolic, secretory, endoplasmic reticulum (C-terminal SEKDEL fusion) and vacuolar (C-terminal KISIA fusion) TG2 versions were transiently expressed in leaves and recombinant protein yields were measured. ER-TG2 and vac-TG2 levels were 9- to 16-fold higher than their cytosolic and secretory counterparts. As second strategy, TG2 variants were co-expressed with a hydrophobic elastin-like polymer (ELP) construct encoding for 36 repeats of the pentapeptide VPGXG in which the guest residue X were V and F in ratio 8:1. Protein bodies (PB) were induced by the ELP, with a consequent two-fold-increase in accumulation of both ER-TG2 and vac-TG2. Subsequently, ER-TG2 and vac-TG2 were produced and purified using immobilized metal ion affinity chromatography. Plant purified ER-TG2 and vac-TG2 were recognized by three anti-TG2 monoclonal antibodies that bind different epitopes proving that plant-produced antigen has immunochemical characteristics similar to those of human TG2. Lastly, an ELISA was performed with sera of CD patients and healthy controls. Both vac-TG2 and ER-TG2 were positively recognized by IgA of CD patients while they were not recognized by serum from non-celiac controls. These results confirmed the usefulness of plant-produced TG2 to

  19. Production of the Main Celiac Disease Autoantigen by Transient Expression in Nicotiana benthamiana.

    PubMed

    Marín Viegas, Vanesa S; Acevedo, Gonzalo R; Bayardo, Mariela P; Chirdo, Fernando G; Petruccelli, Silvana

    2015-01-01

    Celiac Disease (CD) is a gluten sensitive enteropathy that remains widely undiagnosed and implementation of massive screening tests is needed to reduce the long term complications associated to untreated CD. The main CD autoantigen, human tissue transglutaminase (TG2), is a challenge for the different expression systems available since its cross-linking activity affects cellular processes. Plant-based transient expression systems can be an alternative for the production of this protein. In this work, a transient expression system for the production of human TG2 in Nicotiana benthamiana leaves was optimized and reactivity of plant-produced TG2 in CD screening test was evaluated. First, a subcellular targeting strategy was tested. Cytosolic, secretory, endoplasmic reticulum (C-terminal SEKDEL fusion) and vacuolar (C-terminal KISIA fusion) TG2 versions were transiently expressed in leaves and recombinant protein yields were measured. ER-TG2 and vac-TG2 levels were 9- to 16-fold higher than their cytosolic and secretory counterparts. As second strategy, TG2 variants were co-expressed with a hydrophobic elastin-like polymer (ELP) construct encoding for 36 repeats of the pentapeptide VPGXG in which the guest residue X were V and F in ratio 8:1. Protein bodies (PB) were induced by the ELP, with a consequent two-fold-increase in accumulation of both ER-TG2 and vac-TG2. Subsequently, ER-TG2 and vac-TG2 were produced and purified using immobilized metal ion affinity chromatography. Plant purified ER-TG2 and vac-TG2 were recognized by three anti-TG2 monoclonal antibodies that bind different epitopes proving that plant-produced antigen has immunochemical characteristics similar to those of human TG2. Lastly, an ELISA was performed with sera of CD patients and healthy controls. Both vac-TG2 and ER-TG2 were positively recognized by IgA of CD patients while they were not recognized by serum from non-celiac controls. These results confirmed the usefulness of plant-produced TG2 to

  20. Endoscopic evaluation of celiac disease severity and its correlation with histopathological aspects of the duodenal mucosa

    PubMed Central

    Bonatto, Mauro W.; Kotze, Luiz; Orlandoski, Marcia; Tsuchyia, Ricardo; de Carvalho, Carlos A.; Lima, Doryane; Kurachi, Gustavo; Orso, Ivan R.B.; Kotze, Lorete

    2016-01-01

    Background and study aims: Celiac disease (CD) is a chronic systemic autoimmune disorder affecting genetically predisposed individuals, triggered and maintained by the ingestion of gluten. Triggered and maintained by the ingestion of gluten, celiac disease is a chronic systemic autoimmune disorder affecting genetically predisposed individuals. Persistent related inflammation of the duodenal mucosa causes atrophy architecture detectable on esophagogastroduodenoscopy (EGD) and histopathology. We investigated the association between endoscopic features and histopathological findings (Marsh) for duodenal mucosa in celiac disease patients and propose an endoscopic classification of severity. Patients and methods: Between January 2000 and March 2010, an electronic database containing 34,540 EDGs of patients aged > 14 years was searched for cases of CD. Out of 109 cases, 85 met the inclusion criteria: conventional EGD combined with chromoendoscopy, zoom and biopsy. EGD types 0, I and II corresponds to Marsh grades 0, 1 and 2, respectively, while EGD type III corresponds to Marsh grade 3 and 4. Results: Five patients (5.8 %) were EGD I but not Marsh grade 1; 25 patients (29.4 %) were EGD II, 4 of whom (16 %) were classified as Marsh grade 2; and 55 patients (64.7 %) were EGD III, 51 (92.7 %) of whom were classified as Marsh grades 3 and 4. The Spearman correlation coefficient (r = 0.33) revealed a significant association between the methods (P = 0.002). Conclusions: Changes in the duodenal mucosa detected on EGD were significantly and positively associated with histopathologic findings. The use of chromoendoscopy in addition to conventional EGD enhances changes in the duodenal mucosa and permits diagnosis of CD, even in routine examinations. The proposed endoscopic classification is practical and easily reproducible and provides valuable information regarding disease extension. PMID:27556094

  1. Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease.

    PubMed

    Chen, Xi; Hnida, Kathrin; Graewert, Melissa Ann; Andersen, Jan Terje; Iversen, Rasmus; Tuukkanen, Anne; Svergun, Dmitri; Sollid, Ludvig M

    2015-08-28

    Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease.

  2. Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease.

    PubMed

    Chen, Xi; Hnida, Kathrin; Graewert, Melissa Ann; Andersen, Jan Terje; Iversen, Rasmus; Tuukkanen, Anne; Svergun, Dmitri; Sollid, Ludvig M

    2015-08-28

    Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease. PMID:26160175

  3. 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.

  4. Celiac disease as a model for the evolution of multifactorial disease in humans.

    PubMed

    Sams, Aaron; Hawks, John

    2014-01-01

    Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models of disease. Specifically, we conclude that the set of loci underlying CD risk did not cohesively evolve as a response to a single past selection event such as the development of agriculture. Rather, deterministic and stochastic evolutionary processes have both contributed to the present distribution of variation in CD risk loci. Selection has shaped some components of this network, but this selection appears to have occurred at different points in the past. Other parts of the CD risk network have likely arisen due to stochastic processes such as genetic drift.

  5. What People with Celiac Disease Need to Know about Osteoporosis

    MedlinePlus

    ... ligand (RANKL) inhibitor. Resources NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... Pub. No. 16-7897 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  6. New insights into wheat toxicity: Breeding did not seem to contribute to a prevalence of potential celiac disease's immunostimulatory epitopes.

    PubMed

    Ribeiro, Miguel; Rodriguez-Quijano, Marta; Nunes, Fernando M; Carrillo, Jose Maria; Branlard, Gérard; Igrejas, Gilberto

    2016-12-15

    Gluten proteins, namely gliadins, are the primary trigger of the abnormal immune response in celiac disease. It has been hypothesised that modern wheat breeding practices may have contributed to the increase in celiac disease prevalence during the latter half of the 20th century. Our results do not support this hypothesis as Triticum aestivum spp. vulgare landraces, which were not subjected to breeding practices, presented higher amounts of potential celiac disease's immunostimulatory epitopes when compared to modern varieties. Furthermore, high variation between wheat varieties concerning the toxic epitopes amount was observed. We carried out quantitative analysis of gliadin types by RP-HPLC to verify its correlation with the amount of toxic epitopes: ω-type gliadins content explain about 40% of the variation of toxic epitopes in tetraploid wheat varieties. This research provides new insights regarding wheat toxicity and into the controversial idea that human practices may have conducted to an increased exposure to toxic epitopes. PMID:27451149

  7. New insights into wheat toxicity: Breeding did not seem to contribute to a prevalence of potential celiac disease's immunostimulatory epitopes.

    PubMed

    Ribeiro, Miguel; Rodriguez-Quijano, Marta; Nunes, Fernando M; Carrillo, Jose Maria; Branlard, Gérard; Igrejas, Gilberto

    2016-12-15

    Gluten proteins, namely gliadins, are the primary trigger of the abnormal immune response in celiac disease. It has been hypothesised that modern wheat breeding practices may have contributed to the increase in celiac disease prevalence during the latter half of the 20th century. Our results do not support this hypothesis as Triticum aestivum spp. vulgare landraces, which were not subjected to breeding practices, presented higher amounts of potential celiac disease's immunostimulatory epitopes when compared to modern varieties. Furthermore, high variation between wheat varieties concerning the toxic epitopes amount was observed. We carried out quantitative analysis of gliadin types by RP-HPLC to verify its correlation with the amount of toxic epitopes: ω-type gliadins content explain about 40% of the variation of toxic epitopes in tetraploid wheat varieties. This research provides new insights regarding wheat toxicity and into the controversial idea that human practices may have conducted to an increased exposure to toxic epitopes.

  8. Coexistence of Celiac and Crohn's Disease in a Patient Presenting with Chronic Diarrhea.

    PubMed

    Lail, Ghulamullah; Tasneem, Abbas Ali; Butt, Muhammed Osama; Luck, Nasir Hassan; Laeq, Syed Mudassir; Abbas, Zaigham; Mubarak, Muhammed

    2016-06-01

    Celiac disease (CD) is one of the most common causes of malabsorption. It is an immune-mediated disease manifested by diarrhea, steatorrhea, flatulence, and weight loss, caused by ingestion of gluten containing diets. The disease has typical small intestinal biopsy features of villous atrophy, crypt hyperplasia, and intense inflammation of the mucosal layer. The disease is rarely associated with Crohn's disease (CRD). Studies on the impact of CD on the natural history of inflammatory bowel disease (IBD) have shown that the natural course of CRD is not influenced by coexistent CD. We report a case of 54-year female who presented with diarrhea and weight loss. On initial evaluation, CD was diagnosed, and responded to gluten-free diet (GFD). Later on, she developed joint pains and her diarrhea recurred. Further evaluation revealed coexistence of CRD. The treatment of CRD was also initiated and this led to marked improvement in the symptoms of the patient. PMID:27353997

  9. Effect of a Gluten-Free Diet on Cortical Excitability in Adults with Celiac Disease

    PubMed Central

    Bella, Rita; Lanza, Giuseppe; Cantone, Mariagiovanna; Giuffrida, Salvatore; Puglisi, Valentina; Vinciguerra, Luisa; Pennisi, Manuela; Ricceri, Riccardo; D’Agate, Carmela Cinzia; Malaguarnera, Giulia; Ferri, Raffaele; Pennisi, Giovanni

    2015-01-01

    Introduction An imbalance between excitatory and inhibitory synaptic excitability was observed in de novo patients with celiac disease (CD) in a previous study with Transcranial Magnetic Stimulation (TMS), suggesting a subclinical involvement of GABAergic and glutamatergic neurotransmission in asymptomatic patients. The aim of this investigation was to monitor the eventual changes in the same cohort of patients, evaluated after a period of gluten-free diet. Methods Patients were re-evaluated after a median period of 16 months during which an adequate gluten-free diet was maintained. Clinical, cognitive and neuropsychiatric assessment was repeated, as well as cortical excitability by means of single- and paired-pulse TMS from the first dorsal interosseous muscle of the dominant hand. Results Compared to baseline, patients showed a significant decrease of the median resting motor threshold (from 35% to 33%, p<0.01). The other single-pulse (cortical silent period, motor evoked potentials latency and amplitude, central motor conduction time) and paired-pulse TMS measures (intracortical inhibition and intracortical facilitation) did not change significantly after the follow-up period. Antibodies were still present in 7 subjects. Discussion In patients under a gluten-free diet, a global increase of cortical excitability was observed, suggesting a glutamate-mediated functional reorganization compensating for disease progression. We hypothesize that glutamate receptor activation, probably triggered by CD-related immune system dysregulation, might result in a long-lasting motor cortex hyperexcitability with increased excitatory post-synaptic potentials, probably related to phenomena of long-term plasticity. The impact of the gluten-free diet on subclinical neurological abnormalities needs to be further explored. PMID:26053324

  10. Approach to diagnosing celiac disease in patients with low bone mineral density or fragility fractures

    PubMed Central

    Rios, Lorena P.; Khan, Aliya; Sultan, Muhammad; McAssey, Karen; Fouda, Mona A.; Armstrong, David

    2013-01-01

    Abstract Objective To provide clinicians with an update on the diagnosis of celiac disease (CD) and to make recommendations on the indications to screen for CD in patients presenting with low bone mineral density (BMD) or fragility fractures. Quality of evidence A multidisciplinary task force developed clinically relevant questions related to the diagnosis of CD as the basis for a literature search of the MEDLINE, EMBASE, and CENTRAL databases (January 2000 to January 2009) using the key words celiac disease, osteoporosis, osteopenia, low bone mass, and fracture. The existing literature consists of level I and II studies. Main message The estimated prevalence of asymptomatic CD is 2% to 3% in individuals with low BMD. Routine screening for CD is not justified in patients with low BMD. However, targeted screening for CD is recommended for patients who have T-scores of −1.0 or less at the spine or hip, or a history of fragility fractures in association with any CD-related symptoms or conditions; family history of CD; or low urinary calcium levels, vitamin D insufficiency, and raised parathyroid hormone levels despite adequate intake of calcium and vitamin D. Celiac disease testing should be performed while the subject is consuming a gluten-containing diet; initial screening should be performed with human recombinant immunoglobulin (Ig) A tissue transglutaminase or other IgA tissue transglutaminase assays, in association with IgA endomysial antibody immunofluorescence. Duodenal biopsy is necessary to confirm the diagnosis of CD. Human leukocyte antigen typing might assist in confirming or ruling out the diagnosis of CD in cases where serology and histology are discordant. Definitive diagnosis is based on clinical, serologic, and histologic features, combined with a positive response to a gluten-free diet. Conclusion Current evidence does not support routine screening for CD in all patients with low BMD. A targeted case-finding approach is appropriate for patients

  11. An unusual case of hypercalcemia in a patient of concomitant hypoparathyroidism and celiac disease.

    PubMed

    Somani, Shrikant; Kotwal, Narendra; Upreti, Vimal

    2016-01-01

    Milk alkali syndrome has shown resurgence with increase in use of (prescription or non prescription) calcium supplements. Cases of iatrogenic vitamin D intoxication has also increased due to increasing use of high doses of injectable vitamin D formulations by physicians, surgeons, orthopaedicians, gynecologists and other specialties inadvertently. Here, we present an unusual case of a 17-year-old boy who presented with iatrogenic hypercalcemia as a result of combination of milk alkali syndrome with vitamin D intoxication despite being a case of hypoparathyroidism and concomitantly suffering from celiac disease. PMID:27252747

  12. An unusual case of hypercalcemia in a patient of concomitant hypoparathyroidism and celiac disease

    PubMed Central

    Somani, Shrikant; Kotwal, Narendra; Upreti, Vimal

    2016-01-01

    Summary Milk alkali syndrome has shown resurgence with increase in use of (prescription or non prescription) calcium supplements. Cases of iatrogenic vitamin D intoxication has also increased due to increasing use of high doses of injectable vitamin D formulations by physicians, surgeons, orthopaedicians, gynecologists and other specialties inadvertently. Here, we present an unusual case of a 17-year-old boy who presented with iatrogenic hypercalcemia as a result of combination of milk alkali syndrome with vitamin D intoxication despite being a case of hypoparathyroidism and concomitantly suffering from celiac disease. PMID:27252747

  13. Tetany caused by chronic diarrhea in a child with celiac disease: A case report.

    PubMed

    Hurtado-Valenzuela, Jaime Gabriel; Sotelo-Cruz, Norberto; López-Cervantes, Guillermo; de la Barca, Ana María Calderón

    2008-09-23

    There is no awareness about celiac disease (CD) in Mexico. A 2.9 year old mestizo boy was admitted to a Mexican hospital with muscle cramps and fine tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs, stunting and wasting, and presented hypocalcemia, anemia and high titers of serological markers. Diagnosis of CD was confirmed by a duodenal biopsy. After replacement of calcium and a gluten-free diet, the symptoms resolved within 6 weeks. After 2-months, serum analyses, anthropometric data as well as antibodies titers were normal after 4 years. CD screening tests are needed in chronic diarrhea for any ethnicity patients.

  14. Tetany caused by chronic diarrhea in a child with celiac disease: A case report

    PubMed Central

    Hurtado-Valenzuela, Jaime Gabriel; Sotelo-Cruz, Norberto; López-Cervantes, Guillermo; de la Barca, Ana María Calderón

    2008-01-01

    There is no awareness about celiac disease (CD) in Mexico. A 2.9 year old mestizo boy was admitted to a Mexican hospital with muscle cramps and fine tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs, stunting and wasting, and presented hypocalcemia, anemia and high titers of serological markers. Diagnosis of CD was confirmed by a duodenal biopsy. After replacement of calcium and a gluten-free diet, the symptoms resolved within 6 weeks. After 2-months, serum analyses, anthropometric data as well as antibodies titers were normal after 4 years. CD screening tests are needed in chronic diarrhea for any ethnicity patients. PMID:18811963

  15.  An autoimmune polyglandular syndrome complicated with celiac disease and autoimmune hepatitis.

    PubMed

    Dieli-Crimi, Romina; Núñez, Concepción; Estrada, Lourdes; López-Palacios, Natalia

    2016-01-01

     Autoimmune polyglandular syndrome (APS) is a combination of different autoimmune diseases. The close relationship between immune-mediated disorders makes it mandatory to perform serological screening periodically in order to avoid delayed diagnosis of additional autoimmune diseases. We studied a patient with type 1 diabetes (T1D) who later developed an autoimmune thyroid disease (ATD) and was referred to our hospital with a serious condition of his clinical status. The patient was suffering from an advance stage of celiac disease (CD), the delay in its diagnosis and in the establishment of a gluten-free dietled the patient to a severe proteincalorie malnutrition. Later, the patient developed an autoimmune hepatitis (AIH). We consider that clinical deterioration in patients with APS should alert physicians about the possible presence of other immune-mediated diseases. Periodic screening for autoantibodies would help to prevent delayed diagnosis and would improve patient's quality of life. PMID:27236159

  16. An unusual association of three autoimmune disorders: celiac disease, systemic lupus erythematosus and Hashimoto's thyroiditis.

    PubMed

    Boccuti, Viera; Perrone, Antonio; D'Introno, Alessia; Campobasso, Anna; Sangineto, Moris; Sabbà, Carlo

    2016-12-01

    Autoimmune disorders are known to be more frequent in women and often associated each others, but it is rare to see multiple autoimmune diseases in a single patient. Recently, the concept of multiple autoimmune syndrome has been introduced to describe patients with at least three autoimmune diseases. We describe a case of a young man with a clinical history of psychiatric symptoms and celiac disease (CD) who was diagnosed to have other two autoimmune disorders: systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. This case is unusual upon different patterns: the rare combination of the three autoimmune diseases, their appearance in a man and the atypical onset of the diseases with psychiatric symptoms likely to be related either to CD or to SLE. PMID:27383232

  17. The last two millennias echo-catastrophes are the driving forces for the potential genetic advantage mechanisms in celiac disease.

    PubMed

    Aaron, Lerner

    2011-11-01

    Many human genes have adapted to the constant threat of exposure to changing environmental conditions. Balancing selection is the result of an initial stage of positive selection that favors the spread in a population of a new allele until selection opposes its fixation and balanced situation is established. It is suggested that the disadvantageous celiac patients survived the last two millennias echo-catastrophes by adapting to the extreme temperature changes and their consequences in Europe. Genetic selective diversity induced by changing environment, enabled the celiac population to survive. Such a genetic positive selection is represented by the HEF C282Y mutation of hemochromatosis, SH2B3 loci and the HLA celiac disease-associated repertoire, enabling the celiac to overcome iron deficiency anemia and micro pathogen richness, respectively. The increased incidence of those evolutionary events in the celiac patients is a recent phenomenon that occurred in the latest era of the modern human history. The present hypothesis can shed light on additional selective genetic adaptations, echo catastrophe-driven that are at the basis of autoimmune disease-affected population survival and current expansion.

  18. 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.

  19. Enamel organ proteins as targets for antibodies in celiac disease: implications for oral health.

    PubMed

    Sóñora, Cecilia; Arbildi, Paula; Rodríguez-Camejo, Claudio; Beovide, Verónica; Marco, Alicia; Hernández, Ana

    2016-02-01

    Enamel defects in permanent and deciduous teeth may be oral manifestations of celiac disease. Sometimes they are the only sign that points to this underdiagnosed autoimmune pathology. However, the etiology of these specific enamel defects remains unknown. Based on previously reported cross-reactivity of antibodies to gliadin with the enamel proteins, amelogenin and ameloblastin, we analyzed (using immunohistochemistry) the ability of anti-gliadin IgG, produced during untreated disease, to recognize enamel organ structures. We used swine germ teeth as a tissue model because they are highly homologous to human teeth in terms of proteins and development biology. Strong staining of the enamel matrix and of the layer of ameloblasts was observed with serum samples from women with celiac disease; high IgG reactivity was found against both gliadin peptides and enamel matrix protein extract, but there was no IgG reactivity against tissue antigens. In line with these findings, the gamma globulin fraction from gliadin-immunized BALB/c mice showed a similar staining pattern to that of amelogenin-specific staining. These results strongly suggest a pathological role for antibodies to gliadin in enamel defect dentition for both deciduous and permanent teeth, considering that IgG can be transported through the placenta during fetal tooth development.

  20. 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. PMID:27469368

  1. 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.

  2. Does Celiac Disease Influence Survival in Sepsis? A Nationwide Longitudinal Study

    PubMed Central

    Röckert Tjernberg, Anna; Bonnedahl, Jonas; Ludvigsson, Jonas F.

    2016-01-01

    Background Individuals with celiac disease (CD) are at increased risk of sepsis. The aim of this study was to examine whether CD influences survival in sepsis of bacterial origin. Methods Nationwide longitudinal registry-based study. Through data on small intestinal biopsies from Sweden’s 28 pathology departments, we identified 29,096 individuals with CD (villous atrophy, Marsh stage III). Each individual with CD was matched with five population-based controls. Among these, 5,470 had a record of sepsis according to the Swedish Patient Register (1,432 celiac individuals and 4,038 controls). Finally we retrieved data on mortality in sepsis patients through the Swedish Cause of Death Registry. Results CD was associated with a 19% increase in overall mortality after sepsis (95% confidence interval (CI) = 1.09–1.29), with the highest relative risk occurring in children (adjusted hazard ratio (aHR) = 1.62; 95%CI = 0.67–3.91). However, aHR for death from sepsis was lower (aHR = 1.10) and failed to reach statistical significance (95%CI = 0.72–1.69). CD did not influence survival within 28 days after sepsis (aHR = 0.98; 95%CI = 0.80–1.19). Conclusions Although individuals with CD seem to be at an increased risk of overall death after sepsis, that excess risk does not differ from the general excess mortality previously seen in celiac patients in Sweden. CD as such does not seem to influence short-term or sepsis-specific survival in individuals with sepsis and therefore is not an independent risk factor for poor prognosis in sepsis. PMID:27124735

  3. [Design of a genomic, environmental, microbial and metabolomic study on celiac disease: an approach to the future of personalized prevention of celiac disease].

    PubMed

    Serena, Gloria; Leonard, Maureen M; Camhi, Stephanie; Huedo-Medina, Tania B; Fasano, Alessio

    2016-06-01

    Over recent years we have seen rising many clinical and scientific innovations about celiac disease (CE), however the most important innovation that will contribute to change the future of the research and clinic in this field is the natural history of the disease. For many years it has been though that a genetic predisposition and the exposure to gluten were necessary and sufficient to develop CE. Recent studies, however, suggest that the loss of tolerance to gluten may occur in any moment of life upon certain conditions. Furthermore, several environmental factors known to play a role in shaping the intestinal microflora have also been considered related to the development of CE. Delivery mode, the infant diet and the use of antibiotics are included among these factors. To this day no large scale studies have determined if and how the microbiome composition and its metabolomic profile may influence the loss of tolerance to gluten and the consequent development of CE. In this paper we describe a prospective, multi-centric and longitudinal study on infants at risk for CE that will use different techniques to better understand the role of the microbome during the first steps in the development of the autoimmune disease. PMID:27362724

  4. Unusual presentation of arsenic poisoning in a case of celiac disease.

    PubMed

    Hasanato, Rana M; Almomen, AbdulKareem M

    2015-01-01

    Arsenic poisoning may occur from sources other than drinking water such as rice, seafood, or insecticides. Symptoms and signs can be insidious, non-specific, atypical, and easily overlooked. We present a 39-year-old woman with celiac disease who was on gluten-free diet for 8 years and presented with diarrhea, headache, insomnia, loss of appetite, abnormal taste, and impaired short-term memory and concentration, but with no skin lesions. Arsenic concentration in her 24-hour urine was 682.77 micro g/g creatinine (normal < 15). She responded very well to chelation therapy with dimercaptosuccinic acid given orally and recovered within 2 weeks. The suspected source of arsenic poisoning was rice, as drink.ing contaminated ground water is not known in Saudi Arabia and she had not taken seafood. Therefore, arsenic poisoning should be suspected based on the meticulous medical history in cases of patients with celiac disease whose main food is rice and who present with unusual symptoms.

  5. Total oxidant status, total antioxidant capacity and ischemia modified albumin levels in children with celiac disease.

    PubMed

    Sayar, Ersin; Özdem, Sebahat; Uzun, Gülbahar; İşlek, Ali; Yılmaz, Aygen; Artan, Reha

    2015-01-01

    In our study, we aimed to investigate ischemia modified albumin (IMA) as an oxidative stress marker, as well as other oxidant and antioxidant markers that have not been evaluated in children with celiac disease. A total of 37 pediatric patients who were diagnosed with celiac disease (CD) and 29 healthy children were enrolled in this prospective study. We evaluated the IMA, total oxidant status, total antioxidant capacity, sulfhydryl, and advanced oxidation protein products in all of the subjects. We also compared the levels at the time of the diagnosis, and following a gluten-free diet (GFD) in the children with CD. While the IMA and the other oxidant marker levels were significantly higher in the patient group compared to the control group, the antioxidant marker levels were found to be significantly lower in the patient group, compared to the control group. We also determined that the tissue transglutaminase IgA showed a highly positive correlation, and that the IMA showed a moderately positive correlation with the Marsh-Oberhuber histopathological stage. Additionally, the IMA and other oxidant marker levels were significantly lower, while the antioxidant marker levels were significantly higher after the GFD, compared to the pre-diet period. We detected that oxidative stress played a role in the pathogenesis of CD, and that this could be evaluated using oxidative stress markers, which would regress after the GFD. We also detected that IMA is a marker that shows a correlation with the histopathological stage, and may be used in the diagnosis. PMID:27411418

  6. Prevalence of Celiac Disease in Latin America: A Systematic Review and Meta-Regression

    PubMed Central

    Parra-Medina, Rafael; Molano-Gonzalez, Nicolás; Rojas-Villarraga, Adriana; Agmon-Levin, Nancy; Arango, Maria-Teresa; Shoenfeld, Yehuda; Anaya, Juan-Manuel

    2015-01-01

    Background Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in susceptible individuals, and its prevalence varies depending on the studied population. Given that information on CD in Latin America is scarce, we aimed to investigate the prevalence of CD in this region of the world through a systematic review and meta-analysis. Methods and Findings This was a two-phase study. First, a cross-sectional analysis from 981 individuals of the Colombian population was made. Second, a systematic review and meta-regression analysis were performed following the Preferred Reporting Items for Systematic Meta- Analyses (PRISMA) guidelines. Our results disclosed a lack of celiac autoimmunity in the studied Colombian population (i.e., anti-tissue transglutaminase (tTG) and IgA anti-endomysium (EMA)). In the systematic review, 72 studies were considered. The estimated prevalence of CD in Latin Americans ranged between 0.46% and 0.64%. The prevalence of CD in first-degree relatives of CD probands was 5.5%. The coexistence of CD and type 1 diabetes mellitus varied from 4.6% to 8.7%, depending on the diagnosis methods (i.e., autoantibodies and/or biopsies). Conclusions Although CD seems to be a rare condition in Colombians; the general prevalence of the disease in Latin Americans seemingly corresponds to a similar scenario observed in Europeans. PMID:25942408

  7. Unusual presentation of arsenic poisoning in a case of celiac disease.

    PubMed

    Hasanato, Rana M; Almomen, AbdulKareem M

    2015-01-01

    Arsenic poisoning may occur from sources other than drinking water such as rice, seafood, or insecticides. Symptoms and signs can be insidious, non-specific, atypical, and easily overlooked. We present a 39-year-old woman with celiac disease who was on gluten-free diet for 8 years and presented with diarrhea, headache, insomnia, loss of appetite, abnormal taste, and impaired short-term memory and concentration, but with no skin lesions. Arsenic concentration in her 24-hour urine was 682.77 micro g/g creatinine (normal < 15). She responded very well to chelation therapy with dimercaptosuccinic acid given orally and recovered within 2 weeks. The suspected source of arsenic poisoning was rice, as drink.ing contaminated ground water is not known in Saudi Arabia and she had not taken seafood. Therefore, arsenic poisoning should be suspected based on the meticulous medical history in cases of patients with celiac disease whose main food is rice and who present with unusual symptoms. PMID:26336025

  8. Improving outcomes of refractory celiac disease – current and emerging treatment strategies

    PubMed Central

    Woodward, Jeremy

    2016-01-01

    Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. PMID:27536154

  9. Improving outcomes of refractory celiac disease - current and emerging treatment strategies.

    PubMed

    Woodward, Jeremy

    2016-01-01

    Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. PMID:27536154

  10. Exploring anthropometric and laboratory differences in children of varying ethnicities with celiac disease

    PubMed Central

    Rajani, Seema; Alzaben, Abeer; Shirton, Leanne; Persad, Rabindranath; Huynh, Hien Q; Mager, Diana R; Turner, Justine M

    2014-01-01

    BACKGROUND: Celiac disease (CD) is a common autoimmune disorder with an increasing prevalence, including in ethnic minorities. OBJECTIVE: To report the frequency of CD diagnosis in ethnic minorities presenting to a Canadian pediatric celiac clinic and to determine whether ethnic differences exist at diagnosis or follow-up. METHODS: Patients with biopsy-proven CD diagnosed at a multidisciplinary celiac clinic between 2008 and 2011 were identified through the clinic database. Data at referral, and six-month and 12-month follow-ups were collected. These included demographics, self-reported ethnicity, symptoms, anthropometrics and laboratory investigations, including serum immunoglobulin antitissue transglutaminase (aTTG). RESULTS: A total of 272 patients were identified; 80% (n=218) were Caucasian (group 1) and 20% (n=54) were other ethnicities. South Asians (group 2) comprised 81% (n=44) of the minority population. No differences in age or sex were found between the two groups. Group 1 patients presented more often with gastrointestinal symptoms (71% versus 43%; P<0.001), while patients in group 2 presented more often with growth concerns (21% versus 68%; P<0.001). At diagnosis, serum aTTG level was consistently lower in group 1 compared with group 2 (367 IU/mL versus 834 IU/mL; P=0.030). Both groups reported symptom improvement at six months and one year. At the end of one year, aTTG level was more likely to be normal in group 1 compared with group 2 (64% versus 29%; P<0.001). CONCLUSION: Although they represent a minority group, South Asian children comprised a significant proportion of CD patients presenting to a Canadian celiac clinic. South Asian children were more likely to present with growth concerns, which has important implications for timely diagnosis in this population. In addition, the apparent delay in normalization of aTTG levels suggests that careful follow-up and culturally focused education supports should be developed for South Asian children with

  11. Quinoa Well Tolerated in Patients with Celiac Disease

    MedlinePlus

    ... and an active and effective sponsor of educational programming for consumers and physicians alike. About the Institute ... Training Fellows In Training This section is a one-stop-shop for GI Trainees and those interested ...

  12. Genome Sequence of Kocuria palustris Strain CD07_3 Isolated from the Duodenal Mucosa of a Celiac Disease Patient

    PubMed Central

    Nair, Ramesan Girish; Kaur, Gurwinder; Kochhar, Rakesh; Dhawan, Devinder Kumar

    2016-01-01

    We report here the 2.8-Mb genome of Kocuria palustris strain CD07_3 isolated from the duodenal mucosa of a celiac disease (CD) patient. The genome of the bacterium consists of specific virulence factor genes and antibiotic resistance genes that depict its pathogenic potential. PMID:27125478

  13. Folate Insufficiency Due to Celiac Disease in a 49-Year-Old Woman of Southeast Asian-Indian Ethnicity.

    PubMed

    Datta Mitra, Ananya; Gupta, Asha; Jialal, Ishwarlal

    2016-08-01

    The clinical presentation of celiac disease has evolved from chronic diarrhea and malnutrition to mild nutrient insufficiencies. Recently diagnosed adults with celiac disease should be assessed for micronutrient deficiencies because early institution of a gluten-free diet (GFD) prevents morbidity and reduces the incidence of gastrointestinal malignant neoplasms and osteoporosis. In this report, we present the case of a 49-year-old woman of Southeast Asian-Indian descent living in the United States who had folate insufficiency, as manifested by low serum and red blood cell (RBC) folate levels. Further investigation, including serologic testing and intestinal biopsy, confirmed a diagnosis of celiac disease and other nutrient deficiencies. Managing the condition of this patient with folate supplements and implementation of a recommended GFD reversed the folate insufficiency. In conclusion, when serum and/or RBC levels are low in a person of Southeast Asian-Indian descent living in a country with folate fortification of the grain supply, such as the United States, the medical team needs to look for an organic cause, as in our patient, to diagnose and manage celiac disease early and, hopefully, forestall complications. PMID:27406144

  14. Celiac disease: In vitro and in vivo safety and tolerability of wheat-free sorghum food products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Celiac disease is a condition in which genetically predisposed people have an autoimmune reaction to gluten proteins found in all wheat types and closely related cereals such as barley and rye. This reaction causes the formation of autoantibodies and the destruction of the villi in the small intesti...

  15. 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

  16. 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.

  17. 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

  18. 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.

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

    PubMed

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

    2015-01-01

    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. PMID:26345589

  20. Bone Mineral Density at Diagnosis of Celiac Disease and after 1 Year of Gluten-Free Diet

    PubMed Central

    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. PMID:25379519

  1. A functional variant in the CD209 promoter is associated with DQ2-negative celiac disease in the Spanish population

    PubMed Central

    Núñez, C; Rueda, B; Martínez, A; Maluenda, C; Polanco, I; López-Nevot, MA; Ortega, E; Sierra, E; de la Concha, E Gómez; Urcelay, E; Martín, J

    2006-01-01

    AIM: To address the role of CD209 in celiac disease (CD) patients. Non-human leukocyte antigen (HLA) genetic factors in CD predisposition are poorly understood, and environmental factors like infectious pathogens may play a role. CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation. Recently, a functional variant in the promoter of the CD209 gene (-336A/G) has been shown to affect the transcriptional CD209 activity in vitro and it has been associated with a higher susceptibility to/or severity of infection. METHODS: The study population was composed of two case-control cohorts of 103 and 386 CD patients and 312 y 419 healthy controls as well as a panel of 257 celiac families. Genotyping for the -336A/G CD209 promoter polymorphism was performed using a TaqMan 5´ allelic discrimination assay. HLA-DQ was determined by hybridization with allele specific probes. RESULTS: Initially, the case-control and familial studies did not find any association of the -336 A/G CD209 genetic variant with CD susceptibility. However, the stratification by HLA-DQ2 did reveal a significant association of CD209 promoter polymorphism in the HLA-DQ2 (-) group (carrier A vs GG in DQ2 (-) vs DQ2 (+) patients (P = 0.026, OR = 3.71). CONCLUSION: The -336G CD209 allele seems to be involved in CD susceptibility in HLA-DQ2 (-) patients. Our results might suggest a possible role of pathogens in the onset of a minor group of CD patients. PMID:16865785

  2. [Serological tests for celiac disease in Moroccan patients with type 1 diabetes].

    PubMed

    Bourhanbour, Asmaa Drissi; Ouadghiri, Sanae; Benseffaj, Nadia; Essakalli, Malika

    2016-01-01

    Celiac disease (CD) is an autoimmune disease frequently associated with type 1 diabetes (T1D). The prevalence of CD in patients with T1D varies from 3 to 6%. The clinical manifestation of CD in patients with T1D is classified as asymptomatic in about half of cases. Our study aims to determine the frequency of anti-tissue transglutaminase autoantibodies (IgA-tTG) and anti-gliadin antibodies (AGA) in patients with type 1 diabetes in order to early recommend jejunal biopsy and establish a gluten-free diet before the onset of clinical signs and complications of celiac disease. Subjects included in this study were patients with T1D and untreated CD who showed no signs of this disease. The detection of IgG tTG, IgG IgA and IgG AAG was performed using Luminex technology. We enrolled 31 patients. The study involved 16 men and 15 women. IgA AAG were positive in 4(13%) patients and IgG were positive in 7(22,5%) patients. IgA tTG were positive in 3(10%) patients and IgG was positive in one (3%) patient. In our study the association of diabetes type 1 with biomarkers of CD is not uncommon hence the importance of systematic screening for type 1 diabetes. The diagnosis of this atypical and silent CD form is important given the risk of serious complications such as malabsorption and gastrointestinal cancers. PMID:27642442

  3. High Frequency of Haplotype HLA-DQ7 in Celiac Disease Patients from South Italy: Retrospective Evaluation of 5,535 Subjects at Risk of Celiac Disease

    PubMed Central

    Tinto, Nadia; Cola, Arturo; Piscopo, Chiara; Capuano, Marina; Galatola, Martina; Greco, Luigi; Sacchetti, Lucia

    2015-01-01

    Background Celiac disease (CD) has a strong genetic component mainly due to HLA DQ2/DQ8 encoding genes. However, a minority of CD patients are DQ2/DQ8-negative. To address this issue, we retrospectively characterized HLA haplotypes in 5,535 subjects at risk of CD (either relatives of CD patients or subjects with CD-like symptoms) referred to our center during a 10-year period. Methods We identified loci DQA1/DQB1/DRB1 by sequence-specific oligonucleotide-PCR and sequence-specific primer-PCR; anti-transglutaminase IgA/IgG and anti-endomysium IgA by ELISA and indirect immunofluorescence, respectively. Results We diagnosed CD in 666/5,535 individuals, 4.2% of whom were DQ2/DQ8-negative. Interestingly, DQ7 was one of the most abundant haplotypes in all CD patients and significantly more frequent in DQ2/DQ8-negative (38%) than in DQ2/DQ8-positive CD patients (24%) (p<0.05). Conclusion Our data lend support to the concept that DQ7 represents an additive or independent CD risk haplotype with respect to DQ2/DQ8 haplotypes but this finding should be verified in other large CD populations. PMID:26398634

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

    PubMed

    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

  5. Environmental factors in the etiology of type 1 diabetes, celiac disease, and narcolepsy.

    PubMed

    Lernmark, Åke

    2016-07-01

    The etiology of human leukocyte antigen (HLA)-associated organ-specific autoimmune diseases is incomplete. In type 1 diabetes and celiac disease, the strongest associations are with the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, whereas the DQB1*06:02 allele has a strong negative association. In contrast, narcolepsy, especially as recently triggered by the Pandemrix(®) H1N1 vaccine (GlaxoKlineSmith (GSK), Brentford, Middlesex, UK), did not seem to develop without at least one copy of the latter allele. The overall hypothesis is that the role of these different HLA haplotypes, especially in Finland and Sweden, is related to the immune response to infectious agents that are common in these two populations. The high incidence of both type 1 diabetes and celiac disease in Scandinavia may be the result of the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, and the DQB1*06:02 allele are common because they protected people from succumbing to common infections. The timing of dissecting the autoimmune response is critical to understand the possible role of environmental factors. First, an etiological trigger may be a common virus infecting beta cells or with antigens inducing beta-cell cross reactivity. Second, an autoimmune reaction may ensue, perhaps in response to beta-cell apoptosis or autophagy, resulting in autoantigen-specific T cells and autoantibodies. It is critical in at-risk children to dissect the immune response prior to the appearance of autoantibodies in order to identify cellular reactions in response to environmental factors that are able to induce an HLA-associated immune reaction. PMID:27411439

  6. 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

  7. Celiac Disease

    MedlinePlus

    ... You can also eat all plain meat, fish, chicken, legumes, nuts, seeds, oils, milk, cheese, eggs, fruits, ... broths breading (such as the coating on breaded chicken cutlets, etc.) brown rice syrup (often made from ...

  8. Celiac Disease

    MedlinePlus

    ... safe and which are not. previous continue Gluten-Free Foods Here's a quick quiz: Which of these ... wheat. Luckily, you can make or buy gluten-free pizza crust, make fried chicken with a gluten- ...

  9. Multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations

    PubMed Central

    Einarsdottir, Elisabet; Bevova, Marianna R; Zhernakova, Alexandra; Monsuur, Alienke; Koskinen, Lotta LE; Slot, Ruben van't; Mulder, Chris; Mearin, M Luisa; Korponay-Szabo, Ilma R; Kaukinen, Katri; Kurppa, Kalle; Kere, Juha; Mäki, Markku; Wijmenga, Cisca; Saavalainen, Päivi

    2011-01-01

    Celiac disease is an inflammatory enteropathy caused by intolerance to gluten. Previous linkage studies in the Dutch, Finnish and Hungarian populations have revealed a locus on chromosome 6q21-22 conferring susceptibility to celiac disease. This locus has previously been implicated in susceptibility to other autoimmune diseases such as Crohn's disease and type 1 diabetes. We performed fine mapping on 446 independent individuals with celiac disease and 641 controls of Dutch origin, testing 872 tagging SNPs in a 22 Mb region of chromosome 6. The 12 most promising SNPs were followed up in 2071 individuals from 284 Finnish and 357 Hungarian celiac disease families to identify risk variants in this region. Multiple markers in the region were significantly associated with celiac disease in the Dutch material. Two SNPs, rs9391227 and rs4946111, were significantly associated with celiac disease in the Finnish population. The association to rs9391227 represents the strongest association signal found in the Finnish (P=0.003, OR 0.66) as well as the combined Dutch, Finnish and Hungarian populations (P=3.6 × 10−5, OR 0.76). The rs9391227 is situated downstream of the HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1 (HACE1) gene and is contained within a region of strong linkage disequilibrium enclosing HACE1. Two additional, independent, susceptibility variants in the 6q21-22 region were also found in a meta-analysis of the three populations. The 6q21-22 region was confirmed as a celiac disease susceptibility locus and harbors multiple independent associations, some of which may implicate ubiquitin-pathways in celiac disease susceptibility. PMID:21326284

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

    PubMed

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

    2014-12-14

    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.

  11. Guidelines for the diagnosis and treatment of celiac disease in children.

    PubMed

    Jackson Allen, Patricia L

    2004-01-01

    Jennifer, age 2 years, is being seen for her regular 2-year well child visit. You note her weight is only at the 5% and has been dropping percentiles over the past year When you ask her mother about Jennifer's diet, she reports Jennifer is a "picky eater" and often complains of a "stomach ache." Her mother reports her stomach looks "bloated. " Steven, age 7 years, is brought into the clinic because of recurrent abdominal pain with occasional constipation or diarrhea. Steven's mother had been told in the past that he probably had "irritable bowel syndrome" but changes in his diet, occasional use of a laxative, and relaxation techniques have not improved his symptoms. Rebecca, age 12 years, is brought into your clinic because her mother has recently learned that two first cousins have been diagnosed with celiac disease. She is wondering if Rebecca should be screened for this condition since she has heard it runs in families. PMID:15704596

  12. Normal or defective immune response to Hepatitis B vaccine in patients with diabetes and celiac disease

    PubMed Central

    Zanoni, Giovanna; Contreas, Giovanna; Valletta, Enrico; Gabrielli, Oretta; Mengoli, Carlo; Veneri, Dino

    2014-01-01

    A defective production of protective levels of antibodies to Hepatitis B (HB) vaccine is reported to occur in 4–10% of healthy subjects and a correlation with the presence of specific human leukocyte antigen (HLA) molecules, including DQ2, which also confers genetic predisposition to celiac disease (CD) and type I diabetes mellitus (T1DM), has been suggested. The aim of this study was to analyze the serological response to HB vaccine and measles-containing vaccines in 69 diabetic patients (T1DM), 42 patients with celiac disease (CD) and 79 healthy control subjects (CT). The median interval between the third dose of HB vaccine and serum collection was 6.8, 3.5, and 4.7 years for T1DM, CD and CT groups, respectively. 50/69 (72%) T1DM patients, 32/42 (76%) CD patients and 61/79 (77%) CT subjects showed protective anti-HBs antibodies after vaccination, with no statistically significant difference. On the contrary, a lower statistically significant difference was found in the mean HBsAb level of T1DM subjects when compared with the other two groups. No correlation between HLA DQ2 expression in T1DM and vaccine response was detected. The comparison of serological response to measles after vaccination also showed no statistically significant differences in the three groups. Contrasting results between these data and those reported in the literature might be due to differences in the time intervals between vaccination and testing. Prospective studies in pathological and healthy groups with the same age at HBV vaccination and with the same time interval for blood sample collection to determine antibody titers are necessary in order to provide more conclusive data. PMID:25483516

  13. Normal or defective immune response to Hepatitis B vaccine in patients with diabetes and celiac disease.

    PubMed

    Zanoni, Giovanna; Contreas, Giovanna; Valletta, Enrico; Gabrielli, Oretta; Mengoli, Carlo; Veneri, Dino

    2015-01-01

    A defective production of protective levels of antibodies to Hepatitis B (HB) vaccine is reported to occur in 4-10% of healthy subjects and a correlation with the presence of specific human leukocyte antigen (HLA) molecules, including DQ2, which also confers genetic predisposition to celiac disease (CD) and type I diabetes mellitus (T1DM), has been suggested.   The aim of this study was to analyze the serological response to HB vaccine and measles-containing vaccines in 69 diabetic patients (T1DM), 42 patients with celiac disease (CD) and 79 healthy control subjects (CT). The median interval between the third dose of HB vaccine and serum collection was 6.8, 3.5, and 4.7 years for T1DM, CD and CT groups, respectively. 50/69 (72%) T1DM patients, 32/42 (76%) CD patients and 61/79 (77%) CT subjects showed protective anti-HBs antibodies after vaccination, with no statistically significant difference. On the contrary, a lower statistically significant difference was found in the mean HBsAb level of T1DM subjects when compared with the other two groups. No correlation between HLA DQ2 expression in T1DM and vaccine response was detected. The comparison of serological response to measles after vaccination also showed no statistically significant differences in the three groups. Contrasting results between these data and those reported in the literature might be due to differences in the time intervals between vaccination and testing. Prospective studies in pathological and healthy groups with the same age at HBV vaccination and with the same time interval for blood sample collection to determine antibody titers are necessary in order to provide more conclusive data.

  14. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    PubMed Central

    Giorgio, Floriana; Principi, Mariabeatrice; Losurdo, Giuseppe; Piscitelli, Domenico; Iannone, Andrea; Barone, Michele; Amoruso, Annacinzia; Ierardi, Enzo; Di Leo, Alfredo

    2015-01-01

    In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association. PMID:26371035

  15. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    PubMed

    Giorgio, Floriana; Principi, Mariabeatrice; Losurdo, Giuseppe; Piscitelli, Domenico; Iannone, Andrea; Barone, Michele; Amoruso, Annacinzia; Ierardi, Enzo; Di Leo, Alfredo

    2015-09-08

    In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.

  16. [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.

  17. Celiac Disease: A Disorder Emerging from Antiquity, Its Evolving Classification and Risk, and Potential New Treatment Paradigms

    PubMed Central

    Freeman, Hugh J.

    2015-01-01

    Celiac disease is a chronic genetically based gluten-sensitive immune-mediated enteropathic process primarily affecting the small intestinal mucosa. The disorder classically presents with diarrhea and weight loss; however, more recently, it has been characterized by subclinical occult or latent disease associated with few or no intestinal symptoms. Diagnosis depends on the detection of typical histopathological biopsy changes followed by a gluten-free diet response. A broad range of clinical disorders may mimic celiac disease, along with a wide range of drugs and other therapeutic agents. Recent and intriguing archeological data, largely from the Gobleki Tepe region of the Fertile Crescent, indicate that celiac disease probably emerged as humans transitioned from hunter-gatherer groups to societies dependent on agriculture to secure a stable food supply. Longitudinal studies performed over several decades have suggested that changes in the prevalence of the disease, even apparent epidemic disease, may be due to superimposed or novel environmental factors that may precipitate its appearance. Recent therapeutic approaches are being explored that may supplement, rather than replace, gluten-free diet therapy and permit more nutritional options for future management. PMID:25547088

  18. Celiac disease: a disorder emerging from antiquity, its evolving classification and risk, and potential new treatment paradigms.

    PubMed

    Freeman, Hugh J

    2015-01-01

    Celiac disease is a chronic genetically based gluten-sensitive immune-mediated enteropathic process primarily affecting the small intestinal mucosa. The disorder classically presents with diarrhea and weight loss; however, more recently, it has been characterized by subclinical occult or latent disease associated with few or no intestinal symptoms. Diagnosis depends on the detection of typical histopathological biopsy changes followed by a gluten-free diet response. A broad range of clinical disorders may mimic celiac disease, along with a wide range of drugs and other therapeutic agents. Recent and intriguing archeological data, largely from the Gobleki Tepe region of the Fertile Crescent, indicate that celiac disease probably emerged as humans transitioned from hunter-gatherer groups to societies dependent on agriculture to secure a stable food supply. Longitudinal studies per-formed over several decades have suggested that changes in the prevalence of the disease, even apparent epidemic disease, may be due to superimposed or novel environmental factors that may precipitate its appearance. Recent therapeutic approaches are being explored that may supplement, rather than replace, gluten-free diet therapy and permit more nutritional options for future management.

  19. Computer-aided texture analysis combined with experts' knowledge: Improving endoscopic celiac disease diagnosis

    PubMed Central

    Gadermayr, Michael; Kogler, Hubert; Karla, Maximilian; Merhof, Dorit; Uhl, Andreas; Vécsei, Andreas

    2016-01-01

    AIM To further improve the endoscopic detection of intestinal mucosa alterations due to celiac disease (CD). METHODS We assessed a hybrid approach based on the integration of expert knowledge into the computer-based classification pipeline. A total of 2835 endoscopic images from the duodenum were recorded in 290 children using the modified immersion technique (MIT). These children underwent routine upper endoscopy for suspected CD or non-celiac upper abdominal symptoms between August 2008 and December 2014. Blinded to the clinical data and biopsy results, three medical experts visually classified each image as normal mucosa (Marsh-0) or villous atrophy (Marsh-3). The experts’ decisions were further integrated into state-of-the-art texture recognition systems. Using the biopsy results as the reference standard, the classification accuracies of this hybrid approach were compared to the experts’ diagnoses in 27 different settings. RESULTS Compared to the experts’ diagnoses, in 24 of 27 classification settings (consisting of three imaging modalities, three endoscopists and three classification approaches), the best overall classification accuracies were obtained with the new hybrid approach. In 17 of 24 classification settings, the improvements achieved with the hybrid approach were statistically significant (P < 0.05). Using the hybrid approach classification accuracies between 94% and 100% were obtained. Whereas the improvements are only moderate in the case of the most experienced expert, the results of the less experienced expert could be improved significantly in 17 out of 18 classification settings. Furthermore, the lowest classification accuracy, based on the combination of one database and one specific expert, could be improved from 80% to 95% (P < 0.001). CONCLUSION The overall classification performance of medical experts, especially less experienced experts, can be boosted significantly by integrating expert knowledge into computer-aided diagnosis

  20. Robust spectral analysis of videocapsule images acquired from celiac disease patients

    PubMed Central

    2011-01-01

    Background Dominant frequency (DF) analysis of videocapsule endoscopy images is a new method to detect small intestinal periodicities that may result from mechanical rhythms such as peristalsis. Longer periodicity is related to greater image texture at areas of villous atrophy in celiac disease. However, extraneous features and spatiotemporal phase shift may mask DF rhythms. Method The robustness of Fourier and ensemble averaging spectral analysis to compute DF was tested. Videocapsule images from the distal duodenum of 11 celiac patients (frame rate 2/s and pixel resolution 576 × 576) were analyzed. For patients 1, 2, ... 11, respectively, a total of 10, 11, ..., 20 sequential images were extracted from a randomly selected time epoch. Each image sequence was artificially repeated to 200 frames, simulating periodicities of 0.2, 0.18, ..., 0.1Hz, respectively. Random white noise at four different levels, spatiotemporal phase shift, and frames with air bubbles were added. Power spectra were constructed pixel-wise over 200 frames, and an average spectrum was computed from the 576 × 576 individual spectra. The largest spectral peak in the average spectrum was the estimated DF. Error was defined as the absolute difference between actual DF and estimated DF. Results For Fourier analysis, the mean absolute error between estimated and actual DF was 0.032 ± 0.052Hz. Error increased with greater degree of random noise imposed. In contrast, all ensemble average estimates precisely predicted the simulated DF. Conclusions The ensemble average DF estimate of videocapsule images with simulated periodicity is robust to noise and spatiotemporal phase shift as compared with Fourier analysis. Accurate estimation of DF eliminates the need to impose complex masking, extraction, and/or corrective preprocessing measures. PMID:21906318

  1. Computer-aided texture analysis combined with experts' knowledge: Improving endoscopic celiac disease diagnosis

    PubMed Central

    Gadermayr, Michael; Kogler, Hubert; Karla, Maximilian; Merhof, Dorit; Uhl, Andreas; Vécsei, Andreas

    2016-01-01

    AIM To further improve the endoscopic detection of intestinal mucosa alterations due to celiac disease (CD). METHODS We assessed a hybrid approach based on the integration of expert knowledge into the computer-based classification pipeline. A total of 2835 endoscopic images from the duodenum were recorded in 290 children using the modified immersion technique (MIT). These children underwent routine upper endoscopy for suspected CD or non-celiac upper abdominal symptoms between August 2008 and December 2014. Blinded to the clinical data and biopsy results, three medical experts visually classified each image as normal mucosa (Marsh-0) or villous atrophy (Marsh-3). The experts’ decisions were further integrated into state-of-the-art texture recognition systems. Using the biopsy results as the reference standard, the classification accuracies of this hybrid approach were compared to the experts’ diagnoses in 27 different settings. RESULTS Compared to the experts’ diagnoses, in 24 of 27 classification settings (consisting of three imaging modalities, three endoscopists and three classification approaches), the best overall classification accuracies were obtained with the new hybrid approach. In 17 of 24 classification settings, the improvements achieved with the hybrid approach were statistically significant (P < 0.05). Using the hybrid approach classification accuracies between 94% and 100% were obtained. Whereas the improvements are only moderate in the case of the most experienced expert, the results of the less experienced expert could be improved significantly in 17 out of 18 classification settings. Furthermore, the lowest classification accuracy, based on the combination of one database and one specific expert, could be improved from 80% to 95% (P < 0.001). CONCLUSION The overall classification performance of medical experts, especially less experienced experts, can be boosted significantly by integrating expert knowledge into computer-aided diagnosis

  2. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment.

    PubMed

    Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda

    2014-11-01

    Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients.

  3. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment.

    PubMed

    Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda

    2014-11-01

    Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients. PMID:25072743

  4. Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease

    PubMed Central

    Allegretti, Yessica L.; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W.; Chirdo, Fernando G.

    2013-01-01

    The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role. PMID:24058482

  5. Broad MICA/B expression in the small bowel mucosa: a link between cellular stress and celiac disease.

    PubMed

    Allegretti, Yessica L; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W; Chirdo, Fernando G

    2013-01-01

    The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B(+) T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B(+) B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.

  6. Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption

    PubMed Central

    Ghoshal, Uday C.; Mehrotra, Mansi; Kumar, Sunil; Ghoshal, Ujjala; Krishnani, Narendra; Misra, Asha; Aggarwal, Rakesh; Choudhuri, Gourdas

    2012-01-01

    Background & objectives: Aetiology of malabsorption syndrome (MAS) differs in tropical and temperate countries over time; clinical and laboratory parameters may differentiate between various causes. This study was undertaken to investigate the spectrum of MAS among Indian adults and to find out the features that may help to differentiate between TM and celiac disease. Methods: Causes of MAS, and factors differentiating tropical malabsorption (TM) from celiac disease (CD) were determined in 275 patients. Results: Using standard criteria, causes in 275 patients [age 37.5+13.2 yr, 170, (61.5%) male] were, TM 101 (37%), CD 53 (19%), small intestinal bacterial overgrowth 28 (10%), AIDS 15 (5.4%), giardiasis 13 (5%), hypogammaglobulinemia 12 (4%), intestinal tuberculosis 7 (2.5%), strongyloidiasis 6 (2%), immunoproliferative small intestinal disease 5 (2%), Crohn's disease 6 (2%), amyloidosis 4 (1.5%), intestinal lymphangiectasia 3 (1%) and unknown 22 (8%). On univariate analysis, patients with CD were younger than TM (30.6+12 vs. 39.3+12.6 yr, P<0.001), had lower body weight (41.3+11.8 vs. 49.9+11.2 kg, P<0.001), longer diarrhoea duration (median 36 inter-quartile range 17.8-120 vs. 24-months, 8-48, P<0.01), lower stool frequency (6/day, 5-8 vs. 8, 5-10, P<0.05), lower haemoglobin (9.4+3.2 vs. 10.4+2.7 g/dl, P<0.05), higher platelet count (2,58,000, range 1,35,500-3,23,500 vs. 1,60,000, 1,26,000-2,58,000/mm3, P<0.05), and more often had hepatomegaly (9/53, 17% vs. 4/101, 4%, P<0.01), and subtotal or partial villous atrophy (36/50, 72% vs. 28/87, 32%, P<0.001). Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were significant on multivariate analysis. Interpretation & conclusions: TM and CD are common causes of MAS among Indian adults. Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were found to be associated with CD. PMID:23041739

  7. The genetics of celiac disease: A comprehensive review of clinical implications.

    PubMed

    Dieli-Crimi, Romina; Cénit, M Carmen; Núñez, Concepción

    2015-11-01

    Celiac disease (CD) is a complex immune-related disease with a very strong genetic component. Multiple genetic findings over the last decade have added to the already known MHC influence numerous genetic variants associated to CD susceptibility. Currently, it is well-established that 6 MHC and 39 non-MHC loci, including a higher number of independent genetic variants, are associated to disease risk. Moreover, additional regions have been recently implicated in the disease, which would increase the number of involved loci. Together, the firmly described genetic variants account for roughly 31% of CD heritability, being 25% explained by the MHC influence. These new variants represent markers of disease risk and turn the identification of the causal genes and the causal variants inside the associated loci, as well as their precise biological role on the disease, into a major challenge in CD research. Numerous studies have been developed with this aim showing the high impact of risk variants on gene expression. These studies also indicate a central role of CD4(+) T cells in CD pathogenesis and point to B cells as important players, which is in accordance with the key steps highlighted by the immunological models of pathogenesis. We comprehensively summarize the current knowledge about the genetic architecture of CD, characterized by multiple low-risk variants located within diverse loci which are most likely affecting genes with immune-related functions. These findings are leading to a better understanding of CD pathogenesis and helping in the design of new treatments. The repertoire of potential drug targets for CD has largely broadened last years, bringing us closer to get alternative or complementary treatments to the life-long gluten-free diet, the only effective treatment so far. Epigenetics and microbiota are emerging as potent factors modulating disease risk and putatively affecting disease manifestation, which are also being explored as therapeutic targets.

  8. Levels of circulating TNF-related apoptosis-inducing ligand in celiac disease

    PubMed Central

    CELEGHINI, CLAUDIO; NOT, TARCISIO; NORCIO, ALESSIA; MONASTA, LORENZO; SECCHIERO, PAOLA

    2014-01-01

    It has previously been demonstrated that the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL) are significantly lower in patients with type 1 diabetes (T1D) than in normal age- and gender-matched controls. Since celiac disease (CD) is often associated with T1D, a retrospective study was performed to analyze the sera of a cohort of pediatric subjects: i) patients with CD at onset (n=100); ii) patients with potential CD (n=45); iii) patients with CD associated with other auto-immune diseases (n=17); and iv) patients with eosinophilic esophagitis (n=15). Among the patients with CD, 49 were also analyzed after six months on a gluten-free diet, while data were also available for 13 patients after one year on a gluten-free diet. No significant differences were found in the circulating levels of TRAIL between the patients with CD and the patients with either eosinophilic esophagitis or potential CD. Patients with CD associated with other auto-immune diseases showed significantly lower levels of TRAIL when compared with patients with CD alone. The gluten-free diet did not significantly modify the levels of circulating TRAIL at 6 or 12 months. Thus, although T1D and CD share common immunological features, the circulating levels of TRAIL show a significant difference between the two pathologies, and do not appear to be modulated in CD. PMID:25371753

  9. Feasibility of Screening for Type 1 Diabetes and Celiac Disease in a Pediatric Clinic Setting

    PubMed Central

    Gesualdo, Patricia D.; Bautista, Kimberly A.; Waugh, Kathleen C.; Yu, Liping; Norris, Jill M.; Rewers, Marian J.; Baxter, Judith

    2016-01-01

    Objective Type 1 diabetes (T1D) or celiac disease (CD) develops in at least 2% of the general population. Early detection of disease-specific autoimmunity and subsequent monitoring would be possible if screening tests were more widely available. Currently screening for islet autoimmunity is available only in a research setting and CD-specific autoimmunity screening is limited to those in high risk groups. This study assessed the feasibility of incorporating T1D and CD autoantibody screening into a pediatric practice. Methods Patient engagement strategies, blood collection preference, blood sample volume, rate of autoantibody detection in the general population, and parental satisfaction were assessed. Over 5 weeks, research staff recruited 200 patients aged 2–6 yr from two pediatric practices in the Denver area to be screened for six islet autoantibodies (IAs) and the transglutaminase antibody. Results Of the 765 parents approached, 200 (26%) completed the same day screening. Of the 565 subjects who did not complete the screening, 345 expressed interest, but were unable to make a participation decision. A finger stick, compared to a venous draw, was the preferred method of sample collection. Both methods yielded sufficient volume for autoantibody determination. IAs or the transglutaminase antibody were detected in 11 subjects. Parents expressed satisfaction with all aspects of participation. Conclusion The results of this study suggest that it is feasible to conduct this type of screening in a pediatric clinic. Such screening could lead to increased disease awareness and the possible benefits that can result from early detection. PMID:26251221

  10. Determination of B-Cell Epitopes in Patients with Celiac Disease: Peptide Microarrays

    PubMed Central

    Choung, Rok Seon; Marietta, Eric V.; Van Dyke, Carol T.; Brantner, Tricia L.; Rajasekaran, John; Pasricha, Pankaj J.; Wang, Tianhao; Bei, Kang; Krishna, Karthik; Krishnamurthy, Hari K.; Snyder, Melissa R.; Jayaraman, Vasanth; Murray, Joseph A.

    2016-01-01

    Background Most antibodies recognize conformational or discontinuous epitopes that have a specific 3-dimensional shape; however, determination of discontinuous B-cell epitopes is a major challenge in bioscience. Moreover, the current methods for identifying peptide epitopes often involve laborious, high-cost peptide screening programs. Here, we present a novel microarray method for identifying discontinuous B-cell epitopes in celiac disease (CD) by using a silicon-based peptide array and computational methods. Methods Using a novel silicon-based microarray platform with a multi-pillar chip, overlapping 12-mer peptide sequences of all native and deamidated gliadins, which are known to trigger CD, were synthesized in situ and used to identify peptide epitopes. Results Using a computational algorithm that considered disease specificity of peptide sequences, 2 distinct epitope sets were identified. Further, by combining the most discriminative 3-mer gliadin sequences with randomly interpolated3- or 6-mer peptide sequences, novel discontinuous epitopes were identified and further optimized to maximize disease discrimination. The final discontinuous epitope sets were tested in a confirmatory cohort of CD patients and controls, yielding 99% sensitivity and 100% specificity. Conclusions These novel sets of epitopes derived from gliadin have a high degree of accuracy in differentiating CD from controls, compared with standard serologic tests. The method of ultra-high-density peptide microarray described here would be broadly useful to develop high-fidelity diagnostic tests and explore pathogenesis. PMID:26824466

  11. 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.

  12. 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

  13. 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. PMID:27446824

  14. Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease

    PubMed Central

    Forabosco, Paola; Neuhausen, Susan L.; Greco, Luigi; Naluai, Åsa Torinsson; Wijmenga, Cisca; Saavalainen, Päivi; Houlston, Richard S.; Ciclitira, Paul J.; Babron, Marie-Claude; Lewis, Cathryn M.

    2009-01-01

    Objective A meta-analysis of genome-wide linkage studies allows us to summarize the extensive information available from family-based studies, as the field moves into genome-wide association studies. Methods Here we apply the genome scan meta-analysis (GSMA) method, a rank-based, model-free approach, to combine results across eight independent genome-wide linkages performed on celiac disease (CD), including 554 families with over 1,500 affected individuals. We also investigate the agreement between signals we identified from this meta-analysis of linkage studies and those identified from genome-wide association analysis using a hypergeometric distribution. Results Not surprisingly, the most significant result was obtained in the HLA region. Outside the HLA region, suggestive evidence for linkage was obtained at the telomeric region of chromosome 10 (10q26.12-qter; p = 0.00366), and on chromosome 8 (8q22.2-q24.21; p = 0.00491). Testing signals of association and linkage within bins showed no significant evidence for co-localization of results. Conclusion This meta-analysis allowed us to pool the results from available genome-wide linkage studies and to identify novel regions potentially harboring predisposing genetic variation contributing to CD. This study also shows that linkage and association studies may identify different types of disease-predisposing variants. PMID:19622889

  15. Label free targeted detection and quantification of celiac disease immunogenic epitopes by mass spectrometry.

    PubMed

    van den Broeck, Hetty C; Cordewener, Jan H G; Nessen, Merel A; America, Antoine H P; van der Meer, Ingrid M

    2015-04-24

    Celiac disease (CD) is a food-related disease caused by certain gluten peptides containing T-cell stimulating epitopes from wheat, rye, and barley. CD-patients have to maintain a gluten-free diet and are therefore dependent on reliable testing and labeling of gluten-free products. So far, the R5-ELISA is the approved method to detect if food products can be labeled gluten-free. Because the R5-ELISA detects gluten in general, there is a demand for an improved detection method that quantifies specifically CD-epitopes. Therefore, we developed a new method for detection and quantification of CD-epitopes, based on liquid chromatography (LC) coupled to mass spectrometry (MS) in multiple reaction monitoring (MRM) mode. This method enables targeted label free comparative analysis of the gluten proteins present in different wheat varieties and species, and in wheat-based food products. We have tested our method by analyzing several wheat varieties that vary in CD-epitope content, as was shown before using immunoblotting and specific monoclonal antibodies. The results showed that a modern bread wheat variety Toronto contained the highest amounts of CD immunogenic peptides compared with the older bread wheat variety Minaret and the tetraploid wheat variety Dibillik Sinde. Our developed method can detect quantitatively and simultaneously multiple specific CD-epitopes in a high throughput manner. PMID:25795397

  16. Risk of Idiopathic Dilated Cardiomyopathy in 29 000 Patients With Celiac Disease

    PubMed Central

    Emilsson, Louise; Andersson, Bert; Elfström, Peter; Green, Peter H.R.; Ludvigsson, Jonas F.

    2012-01-01

    Background Dilated cardiomyopathy (DCM) is a rare disease of largely unknown origin. Previous studies have suggested an increased prevalence of celiac disease (CD) in patients with DCM. These studies, however, were based on a maximum of 5 patients with both CD and DCM. In the present large Swedish population-based cohort study, we examined the risk of idiopathic DCM in patients with CD determined by small-intestinal histopathology. Methods and Results From 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy, Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments in Sweden. These individuals were compared with 144 429 reference individuals matched for age, sex, calendar year, and county. Data on DCM were obtained through the National Patient Register and confirmed by patient charts and echocardiography data. During follow-up, 17 patients with CD and 52 reference individuals developed idiopathic DCM. Thus, patients with CD were at an increased risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to 3.00), although the risk estimate failed to attain statistical significance (P=0.052). Conclusion This nationwide study found a moderately but not statistically significantly increased risk of idiopathic DCM in patients with biopsy-verified CD. (J Am Heart Assoc. 2012;1:e001594 doi: 10.1161/JAHA.112.001594.) PMID:23130142

  17. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus

    PubMed Central

    Joshi, Rajesh; Madvariya, Monica

    2015-01-01

    Objective: To determine the prevalence of celiac disease (CD) in children with type 1 diabetes mellitus (TIDM) in follow-up in a Tertiary Care Referral Centre in Western India and to describe the clinical features indicative of CD in screened patients of TIDM. Study Design: In this single center observational cross-sectional study, 71 children who were diagnosed with TIDM were subjected to screening for CD with tissue transglutaminase antibody testing. Those who tested positive were offered intestinal biopsy for the confirmation of diagnosis. Clinical profiles of both groups of patients were compared and manifestations of CD were delineated. Results: The study revealed the prevalence of CD (based on serology) in children with Type 1 diabetes as 15.49%. The prevalence of biopsy-confirmed CD was 7.04%. Of the diagnosed CD patients, one-third were symptomatic at the time of screening while the majority was asymptomatic. The major clinical features indicative of CD were intestinal symptoms, anemia, rickets, and short stature. Autoimmune thyroid disease was prevalent in 29.6% of the patients with TIDM followed by CD. Conclusions: The high prevalence of CD in children with Type 1 diabetes emphasizes the need for routine screening programs to be in place for these high-risk populations. The clinical profile of patients with CD further elaborates the indicators of CD and the need to screen for them. PMID:26693431

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease

    PubMed Central

    Einarsdottir, Elisabet; Koskinen, Lotta LE; Dukes, Emma; Kainu, Kati; Suomela, Sari; Lappalainen, Maarit; Ziberna, Fabiana; Korponay-Szabo, Ilma R; Kurppa, Kalle; Kaukinen, Katri; Ádány, Róza; Pocsai, Zsuzsa; Széles, György; Färkkilä, Martti; Turunen, Ulla; Halme, Leena; Paavola-Sakki, Paulina; Not, Tarcisio; Vatta, Serena; Ventura, Alessandro; Löfberg, Robert; Torkvist, Leif; Bresso, Francesca; Halfvarson, Jonas; Mäki, Markku; Kontula, Kimmo; Saarialho-Kere, Ulpu; Kere, Juha; D'Amato, Mauro; Saavalainen, Päivi

    2009-01-01

    Background Association of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases. Methods We studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease. Results Association of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples. Conclusion Our study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated. PMID:19175939

  3. 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

  4. Mass population screening for celiac disease in children: the experience in Republic of San Marino from 1993 to 2009

    PubMed Central

    2013-01-01

    Background Prevalence of celiac disease in developed countries is assessed about 1:100–1:150. The real prevalence is unknown because mass screenings are expensive and difficult to organize. Moreover celiac disease can affect people at every age and studies on asymptomatic subjects at different ages are not comparable. In this study we wanted to know the real prevalence of celiac disease in children in the Republic of San Marino. We also analysed concordance of different tests used and costs of mass screening. Methods The study started in 1993. From 1993 to 1997 children aged 6, 10 and 14 were screened. Since 1997 only children aged 6 were monitored, in order to have a homogeneous population. In fact, every child born since 1980 was taken into account. Children were recruited by classroom lists of students for general paediatric examination. Until 2005 the screening test was based on dosage of antibodies anti-gliadin (AGA) IgA and IgG on venous blood. Since 2006 these tests were replaced by anti-transglutaminase IgA antibodies (ATTG). Anti-endomysial antibodies (EMA) were performed if result of any between either AGA or ATTG tests was positive or borderline; if EMA was positive, then an endoscopy with histological examination was performed to confirm the final diagnosis. Results Attendance to paediatric examination was 96%, submission to blood test was 87%. 42 on 5092 (0,8%; 1:125) children resulted affected by celiac disease. Histology always confirmed diagnosis by serology except for two cases. AGA test (until 2005) yielded 28 on 4304 (0,7% 1:143); ATTG test (since 2006) revealed 14 positive cases on 788 (1,8%; 1:55) leading to a larger percentage of diagnosis. EMA antibodies always confirmed positivity of ATTG. Conclusions Prevalence of celiac disease in children of Republic of San Marino is comparable to other North-European Countries. Sensitivity of ATTG proved much higher than that of anti-gliadin antibodies. Concordance between ATTG and EMA was 100

  5. Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections.

    PubMed

    Mehta, Pooja; Furuta, Glenn T

    2015-08-01

    The gastrointestinal (GI) tract provides an intriguing organ for considering the eosinophil's role in health and disease. The normal GI tract, except for the esophagus, is populated by eosinophils that are present throughout the mucosa, raising the possibility that eosinophils participate in innate mechanisms of defense. However, data from clinical studies associates increased numbers of eosinophils with inflammatory GI diseases, prompting concerns that eosinophils may have a deleterious effect on the gut. We present clinical features of 4 disease processes that have been associated with eosinophilia and suggest areas requiring investigation as to their clinical significance and scientific relevance.

  6. Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

    PubMed Central

    2014-01-01

    Background Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes. Methods We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies. Results Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without. Conclusions The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones. PMID:24565339

  7. A Sensitive Electrochemiluminescence Immunosensor for Celiac Disease Diagnosis Based on Nanoelectrode Ensembles.

    PubMed

    Habtamu, Henok B; Sentic, Milica; Silvestrini, Morena; De Leo, Luigina; Not, Tarcisio; Arbault, Stephane; Manojlovic, Dragan; Sojic, Neso; Ugo, Paolo

    2015-12-15

    We report here the design of a novel immunosensor and its application for celiac disease diagnosis, based on an electrogenerated chemiluminescence (ECL) readout, using membrane-templated gold nanoelectrode ensembles (NEEs) as a detection platform. An original sensing strategy is presented by segregating spatially the initial electrochemical reaction and the location of the immobilized biomolecules where ECL is finally emitted. The recognition scaffold is the following: tissue transglutaminase (tTG) is immobilized as a capturing agent on the polycarbonate (PC) surface of the track-etched templating membrane. It captures the target tissue transglutaminase antibody (anti-tTG), and finally allows the immobilization of a streptavidin-modified ruthenium-based ECL label via reaction with a suitable biotinylated secondary antibody. The application of an oxidizing potential in a tri-n-propylamine (TPrA) solution generates an intense and sharp ECL signal, suitable for analytical purposes. Voltammetric and ECL analyses evidenced that the ruthenium complex is not oxidized directly at the surface of the nanoelectrodes; instead ECL is generated following the TPrA oxidation, which produces the TPrA•+ and TPrA• radicals. With NEEs operating under total overlap diffusion conditions, high local fluxes of these reactive radicals are produced by the nanoelectrodes in the immediate vicinity of the ECL labels, so that they efficiently generate the ECL signal. The radicals can diffuse over short distances and react with the Ru(bpy)32+ label. In addition, the ECL emission is obtained by applying a potential of 0.88 V versus Ag/AgCl, which is about 0.3 V lower than when ECL is initiated by the electrochemical oxidation of Ru(bpy)3(2+). The immunosensor provides ECL signals which scale with anti-tTG concentration with a linearity range between 1.5 ng·mL–1 and 10 μg·mL–1 and a detection limit of 0.5 ng·mL–1. The sensor is finally applied to the analysis of anti-tTG in human

  8. Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort

    PubMed Central

    Sharma, Ashok; Liu, Xiang; Hadley, David; Hagopian, William; Liu, Edwin; Chen, Wei-Min; Onengut-Gumuscu, Suna; Simell, Ville; Rewers, Marian; Ziegler, Anette-G.; Lernmark, Åke; Simell, Olli; Toppari, Jorma; Krischer, Jeffrey P.; Akolkar, Beena; Rich, Stephen S.; Agardh, Daniel; She, Jin-Xiong

    2016-01-01

    Objectives There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prospective cohort study. Methods A total of 424,788 newborns from the US and European general populations and first-degree relatives with type 1 diabetes were screened for specific HLA genotypes. Of these, 21,589 carried 1 of the 9 HLA genotypes associated with increased risk for type 1 diabetes and celiac disease; we followed 8676 of the children in a 15 y prospective follow-up study. Genotype analyses were performed on 6010 children using the Illumina ImmunoChip. Levels of tTGA were measured in serum samples using radio-ligand binding assays; diagnoses of celiac disease were made based on persistent detection of tTGA and biopsy analysis. Data were analyzed using Cox proportional hazards analyses. Results We found 54 single-nucleotide polymorphisms (SNPs) in 5 genes associated with celiac disease (TAGAP, IL18R1, RGS21, PLEK, and CCR9) in time to celiac disease analyses (10−4>P>5.8x10−6). The hazard ratios (HR) for the SNPs with the smallest P values in each region were 1.59, 1.45, 2.23, 2.64, and 1.40, respectively. Outside of regions previously associated with celiac disease, we identified 10 SNPs in 8 regions that could also be associated with the disease (P<10−4). A SNP near PKIA (rs117128341, P = 6.5x10−8, HR = 2.8) and a SNP near PFKFB3 (rs117139146, P<2.8x10−7, HR = 4.9) reached the genome-wide association threshold in subjects from Sweden. Analyses of time to detection of tTGA identified 29 SNPs in 2 regions previously associated with celiac disease (CTLA4, P = 1.3x10−6, HR = 0.76 and LPP, P = 2.8x10−5, HR = .80) and 6 SNPs in 5 regions not previously

  9. Eosinophils in Gastrointestinal disorders- eosinophilic gastrointestinal diseases, celiac disease, inflammatory bowel diseases and parasitic infections

    PubMed Central

    Mehta, Pooja; Furuta, Glenn T.

    2015-01-01

    Synopsis The gastrointestinal tract provides an intriguing organ for considering the eosinophil’s role in health and disease. The normal gastrointestinal (GI) tract, except for the esophagus, is populated by eosinophils that are present throughout the mucosa in varying numbers. This latter fact raises the possibility that eosinophils participate in innate mechanisms of defense. In contrast, a number of clinical studies provide a wealth of data that associates increased numbers of eosinophils with inflammatory GI diseases; these findings prompt concerns that eosinophils may have a deleterious effect on the gut. In this article we present clinical features of 4 disease processes that have been associated with eosinophilia and suggest areas requiring investigation as to their clinical significance and scientific relevance. PMID:26209893

  10. Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution?

    PubMed

    Cenit, María Carmen; Olivares, Marta; Codoñer-Franch, Pilar; Sanz, Yolanda

    2015-08-17

    It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant's gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis.

  11. Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution?

    PubMed Central

    Cenit, María Carmen; Olivares, Marta; Codoñer-Franch, Pilar; Sanz, Yolanda

    2015-01-01

    It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant’s gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis. PMID:26287240

  12. Probiotics and the Microbiome in Celiac Disease: A Randomised Controlled Trial

    PubMed Central

    Myers, Stephen P.; Rolfe, Margaret

    2016-01-01

    Background. There is limited research investigating the composition of the gastrointestinal microbiota in individuals with celiac disease (CoeD) reporting only partial symptom improvement despite adherence to a strict gluten-free diet (GFD). The aim of this research was to determine if the gastrointestinal microbiota could be altered by probiotic bacteria and provide a potential new therapy for this subgroup. Methods. A multicentre RCT was conducted between January and August 2011 in Australia. Participants included 45 people with CoeD reporting only partial symptom improvement despite adherence to a strict GFD for a minimum of 12 months. Participants took 5 g of VSL#™ probiotic formulation (n = 23) or 5 g placebo (n = 22) orally twice daily for 12 weeks. The main outcome measured was the efficacy of the probiotic formula in altering faecal microbiota counts between baseline and week 12. Safety was determined by safety blood and monitoring adverse events. Results. SPSS™ multivariate repeated measures analysis (95th confidence level) revealed no statistically significant changes between the groups in the faecal microbiota counts or blood safety measures over the course of the study. Conclusion. The probiotic formula when taken orally over the 12-week period did not significantly alter the microbiota measured in this population. The trial was registered with Australian and New Zealand Clinical Trials Register ACTRN12610000630011. PMID:27525027

  13. Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients

    PubMed Central

    Rostami-Nejad, Mohammad; Romanos, Jihane; Rostami, Kamran; Ganji, Azita; Ehsani-Ardakani, Mohammad Javad; Bakhshipour, Ali-Reza; Zojaji, Homayoun; Mohebbi, Seyed Reza; Zali, Mohammad-Reza; Wijmenga, Cisca

    2014-01-01

    AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls. METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with ‘biopsy-confirmed’ CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles. RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%). CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population’s susceptibility to CD. PMID:24876751

  14. Transglutaminases: a meeting point for wheat allergy, celiac disease, and food safety.

    PubMed

    Malandain, H

    2005-12-01

    Wheat is the staple cereal in many countries and its uses in manufactured foods are ever growing due to the technological qualities of gluten proteins. Transglutaminases (TG) are ubiquitous enzymes with many functions. They are able to transform proteins by deamidation and/or transamidation. This last reaction can cross-link proteins together. Intestinal tissue TG has been shown to play an important role in two kinds of immune reactions to wheat: celiac disease and wheat-dependent exercise-induced anaphylaxis. In addition, new epitopes have been suspected in cases of anaphylaxis to wheat isolates, a food ingredient consisting mainly of deamidated gluten proteins. As a microbial TG is included in many food technological processes, its safe use should be checked. This assessment must cover not only the safety of the TG itself but also that of the deamidated/cross-linked proteins generated by this enzyme. This article aims at discussing the possible consequences of using TG in food industry in the light of today knowledge about immune reactions to wheat. PMID:16528904

  15. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy

    PubMed Central

    Bottasso Arias, Natalia M.; García, Marina; Bondar, Constanza; Guzman, Luciana; Redondo, Agustina; Chopita, Nestor; Córsico, Betina; Chirdo, Fernando G.

    2015-01-01

    Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs' expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa. PMID:26346822

  16. Probiotics and the Microbiome in Celiac Disease: A Randomised Controlled Trial.

    PubMed

    Harnett, Joanna; Myers, Stephen P; Rolfe, Margaret

    2016-01-01

    Background. There is limited research investigating the composition of the gastrointestinal microbiota in individuals with celiac disease (CoeD) reporting only partial symptom improvement despite adherence to a strict gluten-free diet (GFD). The aim of this research was to determine if the gastrointestinal microbiota could be altered by probiotic bacteria and provide a potential new therapy for this subgroup. Methods. A multicentre RCT was conducted between January and August 2011 in Australia. Participants included 45 people with CoeD reporting only partial symptom improvement despite adherence to a strict GFD for a minimum of 12 months. Participants took 5 g of VSL#™ probiotic formulation (n = 23) or 5 g placebo (n = 22) orally twice daily for 12 weeks. The main outcome measured was the efficacy of the probiotic formula in altering faecal microbiota counts between baseline and week 12. Safety was determined by safety blood and monitoring adverse events. Results. SPSS™ multivariate repeated measures analysis (95th confidence level) revealed no statistically significant changes between the groups in the faecal microbiota counts or blood safety measures over the course of the study. Conclusion. The probiotic formula when taken orally over the 12-week period did not significantly alter the microbiota measured in this population. The trial was registered with Australian and New Zealand Clinical Trials Register ACTRN12610000630011. PMID:27525027

  17. A young man with hemoptysis: Rare association of idiopathic pulmonary hemosiderosis, celiac disease and dilated cardiomyopathy

    PubMed Central

    Khilnani, Gopi C; Jain, Neetu; Tiwari, Pavan; Hadda, Vijay; Singh, Lavleen

    2015-01-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of recurrent diffuse alveolar hemorrhage (DAH) with no specific treatment. Herein, we discuss a case of hemoptysis, who had IPH and other rare associations. A 19-year-old man presented with recurrent hemoptysis, generalized weakness and progressive dyspnea for 3 years. Earlier, he was diagnosed with anemia and was treated with blood transfusions and hematinics. On examination he had pallor, tachycardia and was underweight. Investigations revealed low level of hemoglobin (7.8 g/dl) and iron deficiency. An electrocardiography (ECG) showed sinus tachycardia, interventricular conduction delay and T-wave inversion. Echocardiography revealed dilated cardiomyopathy with left ventricular dysfunction. Computed tomography of the chest demonstrated bilateral diffuse ground glass opacity suggestive of pulmonary hemorrhage. Pulmonary function tests showed restrictive pattern with increased carbon monoxide diffusion. Bronchoalveolar lavage and transbronchial lung biopsy showed hemosiderin-laden macrophages. Patient could recall recurrent episodes of diarrhea in childhood. Serum antitissue transglutamase antibodies were raised (291.66 IU/ml, normal <30 IU/ml). Duodenal biopsy showed subtotal villous atrophy consistent with celiac disease. He was started on gluten-free diet, beta blockers and diuretics. After two years of treatment, he has been showing consistent improvement. Screening for CD is important in patients with IPH. Cardiomyopathy forms rare third association. All three show improvement with gluten-free diet. PMID:25624603

  18. Prevalence of celiac disease in adult patients with refractory functional dyspepsia: Value of routine duodenal biopsy

    PubMed Central

    Giangreco, Emiliano; D’agate, Cinzia; Barbera, Carmelo; Puzzo, Lidia; Aprile, Giuseppe; Naso, Pietro; Bonanno, Giacomo; Russo, Francesco Paolo; Nicoletti, Alessandra; Incarbone, Salvatore; Trama, Giuseppe; Russo, Antonio

    2008-01-01

    AIM: To investigate the prevalence of celiac disease (CD) in adult patients referred to an open access gastroenterology clinic in the south of Italy and submitted to esophago-gastro-duodenoscopy (EGD) for evaluation of refractory functional dyspepsia. METHODS: Seven hundred and twenty six consecutive dyspeptic patients (282 male, 444 female; mean age 39.6 years, range 18-75 years) with unexplained prolonged dyspepsia were prospectively enrolled. Duodenal biopsies were taken and processed by standard staining. Histological evaluation was carried out according to the Marsh-Oberhuber criteria. RESULTS: The endoscopic findings were: normal in 61.2%, peptic lesions in 20.5%, malignancies in 0.5%, miscellaneous in 16.7%. CD was endoscopically diagnosed in 8 patients (1.1%), histologically in 15 patients (2%). The endoscopic features alone showed a sensitivity of 34.8% and specificity of 100%, with a positive predictive value (PPV) of 100% and a negative predictive value (NPP) of 97.9%. CONCLUSION: This prospective study showed that CD has a high prevalence (1:48) in adult dyspeptic patients and suggests the routine use of duodenal biopsy in this type of patient undergoing EGD. PMID:19058330

  19. Survey on computer aided decision support for diagnosis of celiac disease

    PubMed Central

    Hegenbart, Sebastian; Uhl, Andreas; Vécsei, Andreas

    2015-01-01

    Celiac disease (CD) is a complex autoimmune disorder in genetically predisposed individuals of all age groups triggered by the ingestion of food containing gluten. A reliable diagnosis is of high interest in view of embarking on a strict gluten-free diet, which is the CD treatment modality of first choice. The gold standard for diagnosis of CD is currently based on a histological confirmation of serology, using biopsies performed during upper endoscopy. Computer aided decision support is an emerging option in medicine and endoscopy in particular. Such systems could potentially save costs and manpower while simultaneously increasing the safety of the procedure. Research focused on computer-assisted systems in the context of automated diagnosis of CD has started in 2008. Since then, over 40 publications on the topic have appeared. In this context, data from classical flexible endoscopy as well as wireless capsule endoscopy (WCE) and confocal laser endomicrosopy (CLE) has been used. In this survey paper, we try to give a comprehensive overview of the research focused on computer-assisted diagnosis of CD. PMID:25770906

  20. Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients

    PubMed Central

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2016-01-01

    AIM To quantify the presence of villous atrophy in endoscopic images for improved automation. METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy: (1) Statistical and (2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape. RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished. CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients. PMID:27803772

  1. The Prevalence of the Celiac Disease Among Urban Bedouin Population in Israel

    PubMed Central

    Inna, Rudoy; Andrew, Korobeinikov; Hanna, Shalev; Ilia, Volkov

    2012-01-01

    Background Celiac disease (CD) is a common, but often under-diagnosed condition with possible serious complications. CD, having a prevalence of about 1% is more common than once thought. Only limited research is available comparing differences between adults and children. A comprehensive Medline search was conducted. No data was found concerning the prevalence of CD among the adult Bedouin population. Methods The research is retrospective and descriptive. The objective of our research was to determine the prevalence of the CD within adult and child Bedouin populations in urban Israel. A report of all of diagnosed CD patients extracted from the medical computerized information system (“Clicks”). Results In our sample we found the prevalence was 0.51% in children and 0.12% in adults. Conclusion In our opinion, one of reasons for the low prevalence level in the Bedouin community might be that typical CD symptoms are less prominent in Bedouin communities than in other communities. But no doubt hypo-diagnosis does exist. We suppose more advanced research about the nature and typical clinical manifestations of CD within the Bedouin population need to be investigated. Medical personnel working within the Bedouin community needs information concerning CD and the characteristics of diagnosis and treatment in the Bedouin community. The Bedouin community itself needs more information concerning CD and the importance of treatment, which could also improve early diagnosis and compliance.

  2. 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.

  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. Patterns of Population Differentiation and Natural Selection on the Celiac Disease Background Risk Network

    PubMed Central

    Sams, Aaron; Hawks, John

    2013-01-01

    Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution. PMID:23936230

  5. Patterns of population differentiation and natural selection on the celiac disease background risk network.

    PubMed

    Sams, Aaron; Hawks, John

    2013-01-01

    Celiac disease is a common small intestinal inflammatory condition induced by wheat gluten and related proteins from rye and barley. Left untreated, the clinical presentation of CD can include failure to thrive, malnutrition, and distension in juveniles. The disease can additionally lead to vitamin deficiencies, anemia, and osteoporosis. Therefore, CD potentially negatively affected fitness in past populations utilizing wheat, barley, and rye. Previous analyses of CD risk variants have uncovered evidence for positive selection on some of these loci. These studies also suggest the possibility that risk for common autoimmune conditions such as CD may be the result of positive selection on immune related loci in the genome to fight infection. Under this evolutionary scenario, disease phenotypes may be a trade-off from positive selection on immunity. If this hypothesis is generally true, we can expect to find a signal of natural selection when we survey across the network of loci known to influence CD risk. This study examines the non-HLA autosomal network of gene loci associated with CD risk in Europe. We reject the null hypothesis of neutrality on this network of CD risk loci. Additionally, we can localize evidence of selection in time and space by adding information from the genome of the Tyrolean Iceman. While we can show significant differentiation between continental regions across the CD network, the pattern of evidence is not consistent with primarily recent (Holocene) selection across this network in Europe. Further localization of ancient selection on this network may illuminate the ecological pressures acting on the immune system during this critically interesting phase of our evolution.

  6. Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children.

    PubMed

    Snyder, John; Butzner, J Decker; DeFelice, Amy R; Fasano, Alessio; Guandalini, Stefano; Liu, Edwin; Newton, Kimberly P

    2016-09-01

    Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities.

  7. Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant

    PubMed Central

    Almeida, Rodrigo; Ricaño-Ponce, Isis; Kumar, Vinod; Deelen, Patrick; Szperl, Agata; Trynka, Gosia; Gutierrez-Achury, Javier; Kanterakis, Alexandros; Westra, Harm-Jan; Franke, Lude; Swertz, Morris A.; Platteel, Mathieu; Bilbao, Jose Ramon; Barisani, Donatella; Greco, Luigi; Mearin, Luisa; Wolters, Victorien M.; Mulder, Chris; Mazzilli, Maria Cristina; Sood, Ajit; Cukrowska, Bozena; Núñez, Concepción; Pratesi, Riccardo; Withoff, Sebo; Wijmenga, Cisca

    2014-01-01

    Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10−49), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10−44). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10−49), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD. PMID:24334606

  8. Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children.

    PubMed

    Snyder, John; Butzner, J Decker; DeFelice, Amy R; Fasano, Alessio; Guandalini, Stefano; Liu, Edwin; Newton, Kimberly P

    2016-09-01

    Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities. PMID:27565547

  9. Genome-wide linkage analysis for celiac disease in North American families.

    PubMed

    Neuhausen, Susan L; Feolo, Mike; Camp, Nicola J; Farnham, James; Book, Linda; Zone, John J

    2002-07-22

    Celiac disease (CD) is an autoimmune disease caused by sensitivity to the dietary protein gluten. It has a prevalence of 1 in 250 in the United States. Multiple-case families are common with a risk to siblings from 10-12%. Previous linkage studies have found no significant evidence for linkage other than to HLA. In this study, we performed a genome-wide search on 62 families with at least two cases of CD to identify non-HLA loci for CD. Two-point and multipoint parametric and nonparametric analyses were performed on the entire set of families and on sets stratified by the HLA genotype. Accounting for multiple testing, we found genome-wide intermediate linkage evidence at 18q (heterogeneity LOD (HLOD) = 3.6) and at 3p (HLOD = 3.2) and suggestive evidence at 5p (HLOD = 2.7). Good consensus between two-point and multipoint evidence was not found, and after genotyping with new markers in these regions, our results were inconclusive. The 18q region had intermediate two-point evidence, but weak multipoint evidence. At 3p and 5p, the addition of follow-up markers added flanking support, yet multipoint evidence was still lacking. Our results indicate that multipoint analyses may be hindered by the complexity of CD. Multipoint analyses are not robust to model misspecification, and further development of models is needed. Additional study of these and other families is necessary to validate or rule out the regions implicated in this study.

  10. A Canadian Study toward Changing Local Practice in the Diagnosis of Pediatric Celiac Disease

    PubMed Central

    Rajani, Seema; Huynh, Hien Q.; Shirton, Leanne; Kluthe, Cheryl; Spady, Donald; Prosser, Connie; Meddings, Jon; Rempel, Gwen R.; Persad, Rabindranath; Turner, Justine M.

    2016-01-01

    Background. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition endorses serological diagnosis (SD) for pediatric celiac disease (CD). The objective of this study was to pilot SD and to prospectively evaluate gastrointestinal permeability and mucosal inflammation at diagnosis and after one year on the gluten-free diet (GFD). We hypothesized that SD would be associated with similar short term outcomes as ED. Method. Children, 3–17 years of age, referred for possible CD were eligible for SD given aTTG level ≥200 U/mL, confirmed by repeat aTTG and HLA haplotypes. Gastrointestinal permeability, assessed using sugar probes, and inflammation, assessed using fecal calprotectin (FC), at baseline and after one year on a GFD were compared to patients who had ED. Results. Enrolled SD (n = 40) and ED (n = 48) patients had similar demographics. ED and SD groups were not different in baseline lactulose: mannitol ratio (L : M) (0.049 versus 0.034; p = 0.07), fractional excretion of sucrose (%FES; 0.086 versus 0.092; p = 0.44), or fecal calprotectin (FC; 89.6 versus 51.4; p = 0.05). At follow-up, urine permeability improved and was similar between groups, L : M (0.022 versus 0.025; p = 0.55) and %FES (0.040 versus 0.047; p = 0.87) (p > 0.05). FC improved but remained higher in the SD group (37.1 versus 15.9; p = 0.04). Conclusion. Patients on the GFD showed improved intestinal permeability and mucosal inflammation regardless of diagnostic strategy. This prospective study supports that children diagnosed by SD have resolving mucosal disease early after commencing a GFD. PMID:27446854

  11. A Canadian Study toward Changing Local Practice in the Diagnosis of Pediatric Celiac Disease.

    PubMed

    Rajani, Seema; Huynh, Hien Q; Shirton, Leanne; Kluthe, Cheryl; Spady, Donald; Prosser, Connie; Meddings, Jon; Rempel, Gwen R; Persad, Rabindranath; Turner, Justine M

    2016-01-01

    Background. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition endorses serological diagnosis (SD) for pediatric celiac disease (CD). The objective of this study was to pilot SD and to prospectively evaluate gastrointestinal permeability and mucosal inflammation at diagnosis and after one year on the gluten-free diet (GFD). We hypothesized that SD would be associated with similar short term outcomes as ED. Method. Children, 3-17 years of age, referred for possible CD were eligible for SD given aTTG level ≥200 U/mL, confirmed by repeat aTTG and HLA haplotypes. Gastrointestinal permeability, assessed using sugar probes, and inflammation, assessed using fecal calprotectin (FC), at baseline and after one year on a GFD were compared to patients who had ED. Results. Enrolled SD (n = 40) and ED (n = 48) patients had similar demographics. ED and SD groups were not different in baseline lactulose: mannitol ratio (L : M) (0.049 versus 0.034; p = 0.07), fractional excretion of sucrose (%FES; 0.086 versus 0.092; p = 0.44), or fecal calprotectin (FC; 89.6 versus 51.4; p = 0.05). At follow-up, urine permeability improved and was similar between groups, L : M (0.022 versus 0.025; p = 0.55) and %FES (0.040 versus 0.047; p = 0.87) (p > 0.05). FC improved but remained higher in the SD group (37.1 versus 15.9; p = 0.04). Conclusion. Patients on the GFD showed improved intestinal permeability and mucosal inflammation regardless of diagnostic strategy. This prospective study supports that children diagnosed by SD have resolving mucosal disease early after commencing a GFD. PMID:27446854

  12. Infant feeding and risk of developing celiac disease: a systematic review

    PubMed Central

    Silano, Marco; Agostoni, Carlo; Sanz, Yolanda; Guandalini, Stefano

    2016-01-01

    Objective To review the evidence for the association of breast feeding, breastfeeding duration or the timing of gluten introduction and the later development of celiac disease (CD). Design Systematic review. Methods We searched MEDLINE, via PubMed, EMBASE and Web of Science, for studies published up to 31 August 2015 investigating the association of breastfeeding duration, breast feeding at the moment of gluten introduction or the timing of gluten introduction and the later development of CD. Prospective studies had to enrol infants/children at high risk of CD. For retrospective studies, participants had to be children or adults with CD. The paper quality was assessed by means of a GRADE score and the bias risk was assessed by the Newcastle-Ottawa Scale (for observational cohort studies) and Cochrane Collaboration's tool (for randomised trials). Results Out of 149 retrieved papers, 48 were considered in depth and 16 were included in this review (9 were prospective and 2 were interventional). We found that neither duration of breastfeeding nor breastfeeding at time of gluten introduction nor the delayed introduction of gluten during weaning were effective in preventing later development of CD. Conclusions Currently, there is no evidence on the optimal breastfeeding duration or the effects of avoiding early (<4 months of age) or late (≥6 or even at 12 months) gluten introduction in children at risk of CD. Accordingly, no specific general recommendations about gluten introduction or optimal breastfeeding duration can be presently provided on evidence-based criteria in order to prevent CD. PMID:26810996

  13. Gender and Racial Disparities in Duodenal Biopsy to Evaluate For Celiac Disease

    PubMed Central

    Lebwohl, Benjamin; Tennyson, Christina A.; Holub, Jennifer L.; Lieberman, David A.; Neugut, Alfred I.; Green, Peter H.R.

    2012-01-01

    Background Celiac disease (CD) is common but under-diagnosed in the United States. Serological screening studies indicate that, although CD occurs at the same frequency in both genders, women are diagnosed more frequently than men (2:1). CD is less frequently diagnosed among black patients, though the seroprevalence in this group is not known. Objective to measure the rates of duodenal biopsy during esophagogastroeduodenoscopy (EGD) for symptoms consistent with CD. Design Retrospective cohort study. Setting Clinical Outcomes Research Initiative National Endoscopy Database, spanning the years 2004–2009. Patients Adults undergoing EGD for the indication of diarrhea, anemia, iron deficiency, or weight loss, in which the endoscopic appearance of the upper gastrointestinal tract was normal. Main outcome measurement performance of duodenal biopsy. Results Of 13,091 individuals (58% females, 9% blacks) who met the inclusion criteria, duodenal biopsy was performed in 43%, 45% of females and 39% of males (p<0.0001). Blacks underwent duodenal biopsy in 28% of EGD’s, compared to 44% for whites (p<0.0001). On multivariate analysis, male gender (OR 0.81 95%CI 0.75–0.88), older age (OR for ≥70 compared to 20–49 0.51 95%CI 0.46–0.57), and black race (OR 0.55 95%CI 0.48–0.64) were associated with decreased odds of duodenal biopsy. Limitations Lack of histopathologic correlation with CD prevalence. Conclusions In this multi-region endoscopy database spanning 2004–2009, rates of duodenal biopsy increased modestly over time, but overall remain low in patients with possible clinical indications for biopsy. Non-performance of duodenal biopsy during endoscopy may be contributing to the under-diagnosis of CD in the United States. PMID:22732871

  14. Late diagnosis of celiac disease in an asymptomatic infant with growth failure.

    PubMed

    Bozzola, Mauro; Bozzola, Elena; Pagani, Sara; Mascolo, Amelia; Porto, Rossella; Meazza, Cristina

    2014-01-15

    The clinical spectrum for celiac disease (CD) is broad and includes cases with either typical (intestinal) or atypical (extraintestinal) features, often making the diagnosis of CD very difficult.We describe the case of a girl presenting with stunted growth and malnourishment. She was evaluated at 14 months for decreased growth rate without any signs of gastrointestinal, renal or endocrine disorders. She was evaluated for CD, but resulted negative for anti-tTG antibodies.At the age of 4.1 years, she exhibited basal dental enamel hypoplasia, iron deficiency anaemia despite repeated iron supplementation, with persistent reduced height (-2.79 SDS), BMI (-0.76 SDS), growth velocity (-1.79 SDS) and delayed bone age (1.5 year). The CD screening was repeated and very high anti-tTG-IgA (128 IU/ml, normal values < 7 IU/ml) and anti-tTG-IgG (77 IU/ml, normal values < 7 IU/ml) values were found. HLA genotyping revealed an HLA DQ2 haplotype. A duodenal biopsy revealed severe villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes (> 40 IELs/100 epithelial cells) confirming the diagnosis of CD. A gluten-free diet was started and after only four months, her growth velocity increased from 4.83 cm/year (-1.79 SDS) to 6.53 cm/year (-0.15 SDS).In conclusion, we report the development of a positive serology for CD in an asymptomatic child with growth retardation, who previously was investigated for CD and resulted negative. Therefore, when faced with retarded growth in young patients, after excluding other malabsorption conditions and even when CD serological markers are negative, the paediatric endocrinologist should request HLA genotyping, before the intestinal biopsy, in order to check for the presence of risk alleles.

  15. Excitability of the Motor Cortex in De Novo Patients with Celiac Disease

    PubMed Central

    Pennisi, Giovanni; Lanza, Giuseppe; Giuffrida, Salvatore; Vinciguerra, Luisa; Puglisi, Valentina; Cantone, Mariagiovanna; Pennisi, Manuela; D'Agate, Carmela Cinzia; Naso, Pietro; Aprile, Giuseppe; Malaguarnera, Giulia; Ferri, Raffaele; Bella, Rita

    2014-01-01

    Introduction Celiac disease (CD) may initially present as a neurological disorder or may be complicated by neurological changes. To date, neurophysiological studies aiming to an objective evaluation of the potential central nervous system involvement in CD are lacking. Objective To assess the profile of cortical excitability to Transcranial Magnetic Stimulation (TMS) in a group of de novo CD patients. Materials and methods Twenty CD patients underwent a screening for cognitive and neuropsychiatric symptoms by means of the Mini Mental State Examination and the Structured Clinical Interview for DSM-IV Axis I Disorders, respectively. Instrumental exams, including electroencephalography and brain computed tomography, were also performed. Cortico-spinal excitability was assessed by means of single and paired-pulse TMS using the first dorsal interosseus muscle of the dominant hand. TMS measures consisted of resting motor threshold, motor evoked potentials, cortical silent period (CSP), intracortical inhibition (ICI) and facilitation (ICF). None of the CD was on gluten-free diet. A group of 20 age-matched healthy controls was used for comparisons. Results CD showed a significantly shorter CSP (78.0 vs 125.0 ms, p<0.025), a reduced ICI (0.3 vs 0.2, p<0.045) and an enhanced ICF (1.1 vs 0.7, p<0.042) compared to controls. A dysthymic disorder was identified in five patients. The effect size between dysthymic and non-dysthymic CD patients indicated a low probability of interference with the CSP (Cohen's d -0.414), ICI (-0.278) and ICF (-0.292) measurements. Conclusion A pattern of cortical excitability characterized by “disinhibition” and “hyperfacilitation” was found in CD patients. Immune system dysregulation might play a central role in triggering changes of the motor cortex excitability. PMID:25062250

  16. Decreased Risk of Celiac Disease in Patients With Helicobacter pylori Colonization

    PubMed Central

    Lebwohl, Benjamin; Blaser, Martin J.; Ludvigsson, Jonas F.; Green, Peter H. R.; Rundle, Andrew; Sonnenberg, Amnon; Genta, Robert M.

    2013-01-01

    The prevalence of celiac disease (CD) has increased in recent decades without a clear explanation. The “hygiene hypothesis” theorizes that decreased exposure to bacterial antigens may trigger autoimmunity. We aimed to determine whether Helicobacter pylori infection and CD were associated among patients undergoing upper gastrointestinal endoscopy. We performed a cross-sectional study of patients who underwent esophagogastroduodenoscopy with submission of gastric and duodenal biopsies to Miraca Life Sciences, Inc. (Irving, Texas), a US commercial pathology laboratory, during a 4.5-year period (January 2008–June 2012). We compared the prevalence of H. pylori in CD patients with that in persons without CD. We performed multiple logistic regression analysis, adjusting odds ratios for patient age, gender, and racial, ethnic, and socioeconomic factors. Among 136,179 patients, a total of 2,689 (2.0%) had CD. H. pylori prevalence was significantly lower in patients with CD (4.4%) than in those without CD (8.8%; P < 0.0001). After adjustment for the above covariates, this inverse relationship remained strong (adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.40, 0.58). The relationships were similar in men (unadjusted OR = 0.51, 95% CI: 0.38, 0.69) and women (unadjusted OR = 0.46, 95% CI: 0.36, 0.58) and in all age groups. We conclude that H. pylori presence and CD are inversely associated, a relationship that persists after adjustment for socioeconomic factors. Future studies should address whether H. pylori modulates immune responses to ingested gluten. PMID:24124196

  17. Vitamin and Mineral Deficiencies Are Highly Prevalent in Newly Diagnosed Celiac Disease Patients

    PubMed Central

    Wierdsma, Nicolette J.; van Bokhorst-de van der Schueren, Marian A. E.; Berkenpas, Marijke; Mulder, Chris J. J.; van Bodegraven, Ad A.

    2013-01-01

    Malabsorption, weight loss and vitamin/mineral-deficiencies characterize classical celiac disease (CD). This study aimed to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult CD-patients in the Netherlands. Newly diagnosed adult CD-patients were included (n = 80, 42.8 ± 15.1 years) and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations. Nutritional status and serum concentrations of folic acid, vitamin A, B6, B12, and (25-hydroxy) D, zinc, haemoglobin (Hb) and ferritin were determined (before prescribing gluten free diet). Almost all CD-patients (87%) had at least one value below the lower limit of reference. Specifically, for vitamin A, 7.5% of patients showed deficient levels, for vitamin B6 14.5%, folic acid 20%, and vitamin B12 19%. Likewise, zinc deficiency was observed in 67% of the CD-patients, 46% had decreased iron storage, and 32% had anaemia. Overall, 17% were malnourished (>10% undesired weight loss), 22% of the women were underweight (Body Mass Index (BMI) < 18.5), and 29% of the patients were overweight (BMI > 25). Vitamin deficiencies were barely seen in healthy controls, with the exception of vitamin B12. Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. In conclusion, vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment. PMID:24084055

  18. Hyper-CK-emia in pediatric celiac disease: prevalence and clinical importance.

    PubMed

    Selimoglu, Mukadder Ayse; Ertekin, Vildan; Altinkaynak, Sevin

    2007-08-01

    Hyper-transaminasemia (HT) is a well-known laboratory sign of celiac disease (CD); however, hyper-creatine phosphokinase (CK)-emia (HCK) is not so familiar. As there are reported cases of myopathy associated CD in the literature, we aimed to investigate serum CK levels of children with CD. Newly diagnosed 126 children were included. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and CK levels were determined. Mean age was 8.7+/-4.4 years (11 mo to 18 y). Of patients, 77 (61.1%) had classic form, 49 (38.9%) had atypical form. Elevated levels of AST, ALT, and CK, respectively, were found in 65 (51.6%), 45 (35.7%), and 50 (39.7%) patients. Isolated HCK was detected in 9 (7.1%) patients. AST, ALT, and CK were all elevated in 29 (23.0%) children. Mean serum AST, ALT, and CK levels were found as 56.1+/-53.7 U/L (11 to 403), 44.7+/-44.0 U/L (7 to 290), and 258.0+/-686.5 U/L (36 to 5956), respectively. In 95 (75.4%) children, AST/ALT value was greater than 1, and in 19 (15.1%) it was greater than 2. We found positive correlations with the level of CK and AST, and ALT (P=0.01). CK level was inversely correlated with hemoglobin and cholesterol levels (P=0.013 and 0.007). In conclusion, this is the first study, which determined elevated serum levels of CK in CD and demonstrated that HCK is as common as HT in children with CD. We emphasize that HT seen in CD is not necessarily a sign of liver injury, but may also be due to myopathy. PMID:17667050

  19. Celiac disease: role of intestinal compartments in the mucosal immune response.

    PubMed

    Iacomino, Giuseppe; Marano, Angela; Stillitano, Ilaria; Aufiero, Vera Rotondi; Iaquinto, Gaetano; Schettino, Michele; Masucci, Armando; Troncone, Riccardo; Auricchio, Salvatore; Mazzarella, Giuseppe

    2016-01-01

    Different approaches have been used to study the pattern of cytokines in celiac disease (CD). Laser capture microdissection (LCM) is a powerful tool for the isolation of specific tissue compartments. We aimed to investigate the mucosal immune response that takes place in different intestinal compartments of CD patients, dissected by LCM, analyzing cytokine expression profile. Frozen section of jejunum was obtained from 15 untreated CD and 15 control. Surface epithelium and lamina propria compartment were isolated by LCM. RNA from each LCM sample was extracted and, after a retrotranscription step, messenger RNA levels for MxA, IL-15, TNF-α, IFN-γ, IL-17α, IL-21, IL-10, and TGF-β were determined by quantitative reverse transcriptase-PCR. Increased gene expression levels of MxA, IL-15, TNF-α, IL-10, and TGF-β was observed in the surface epithelium of untreated CD with respect to control. Furthermore, all the cytokines investigated were upregulated in the lamina propria of untreated CD as compared to control. Within the untreated CD group the expression of IL-15 was higher, in the surface epithelium than in the lamina propria, whereas the expression levels of IL-17 and IL-21 were higher in the lamina propria than in the surface epithelium. Finally, high levels of IL-10 and TGF-β were detected in both compartments of untreated CD biopsies. In CD, surface epithelium and lamina propria compartments, play a prominent role in determining innate and adaptive immunity, respectively. Conversely, surface epithelium and lamina propria produce high levels of anti-inflammatory cytokines, suggesting that both compartments are involved in the immunoregulatory response. PMID:26541753

  20. Different Gene Expression Signatures in Children and Adults with Celiac Disease

    PubMed Central

    López-Palacios, N.; Bodas, A.; Dema, B.; Fernández-Arquero, M.; González-Pérez, B.; Salazar, I.; Núñez, C.

    2016-01-01

    Celiac disease (CD) is developed after gluten ingestion in genetically susceptible individuals. It can appear at any time in life, but some differences are commonly observed between individuals with onset early in life or in adulthood. We aimed to investigate the molecular basis underlying those differences. We collected 19 duodenal biopsies of children and adults with CD and compared the expression of 38 selected genes between each other and with the observed in 13 non-CD controls matched by age. A Bayesian methodology was used to analyze the differences of gene expression between groups. We found seven genes with a similarly altered expression in children and adults with CD when compared to controls (C2orf74, CCR6, FASLG, JAK2, IL23A, TAGAP and UBE2L3). Differences were observed in 13 genes: six genes being altered only in adults (IL1RL1, CD28, STAT3, TMEM187, VAMP3 and ZFP36L1) and two only in children (TNFSF18 and ICOSLG); and four genes showing a significantly higher alteration in adults (CCR4, IL6, IL18RAP and PLEK) and one in children (C1orf106). This is the first extensive study comparing gene expression in children and adults with CD. Differences in the expression level of several genes were found between groups, being notorious the higher alteration observed in adults. Further research is needed to evaluate the possible genetic influence underlying these changes and the specific functional consequences of the reported differences. PMID:26859134

  1. Mortality rate in children born to mothers and fathers with celiac disease: a nationwide cohort study.

    PubMed

    Zugna, Daniela; Richiardi, Lorenzo; Stephansson, Olof; Cnattingius, Sven; Ludvigsson, Jonas F

    2013-06-15

    Celiac disease (CD) is associated with increased mortality rate and adverse pregnancy outcome, but little is known about offspring mortality rate. In this nationwide retrospective cohort study, we identified persons whose biopsy-verified CD was diagnosed in Sweden in 1969-2008. We compared mortality rates in children born to mothers with and without CD (n = 16,121 vs. n = 61,782) and children born to fathers with and without CD (n = 9,289 vs. n = 32,984). Median age of offspring at end of follow-up was 28.7 (range, 16.7-39.7) years. We also examined mortality rates in children born to mothers with undiagnosed CD (later CD diagnosis; n = 12,919) and diagnosed CD (n = 3,202) to determine if intrauterine exposures associated with CD could affect offspring mortality rate. We estimated hazard ratios for death by using Cox regression. Death rates were independent of maternal CD (60 deaths per 100,000 person-years in children of mothers with CD, vs. 54 in controls) and paternal CD (53 deaths per 100,000 person-years in children of fathers with CD, vs. 53 in controls). Corresponding adjusted hazard ratios were 1.09 (95% confidence interval: 0.95, 1.26) for maternal CD and 1.02 (95% confidence interval: 0.85, 1.23) for paternal CD. Death rates were similar in children born to mothers with undiagnosed CD and in children whose mothers had diagnosed CD during pregnancy. Parental CD does not seem to influence mortality rate in offspring, which suggests that neither genetic influences of CD nor intrauterine conditions have adverse effects on offspring mortality rate.

  2. Automatic classification of small bowel mucosa alterations in celiac disease for confocal laser endomicroscopy

    NASA Astrophysics Data System (ADS)

    Boschetto, Davide; Di Claudio, Gianluca; Mirzaei, Hadis; Leong, Rupert; Grisan, Enrico

    2016-03-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to gluten and similar proteins, affecting genetically susceptible persons, increasing their risk of different complications. Small bowels mucosa damage due to CD involves various degrees of endoscopically relevant lesions, which are not easily recognized: their overall sensitivity and positive predictive values are poor even when zoom-endoscopy is used. Confocal Laser Endomicroscopy (CLE) allows skilled and trained experts to qualitative evaluate mucosa alteration such as a decrease in goblet cells density, presence of villous atrophy or crypt hypertrophy. We present a method for automatically classifying CLE images into three different classes: normal regions, villous atrophy and crypt hypertrophy. This classification is performed after a features selection process, in which four features are extracted from each image, through the application of homomorphic filtering and border identification through Canny and Sobel operators. Three different classifiers have been tested on a dataset of 67 different images labeled by experts in three classes (normal, VA and CH): linear approach, Naive-Bayes quadratic approach and a standard quadratic analysis, all validated with a ten-fold cross validation. Linear classification achieves 82.09% accuracy (class accuracies: 90.32% for normal villi, 82.35% for VA and 68.42% for CH, sensitivity: 0.68, specificity 1.00), Naive Bayes analysis returns 83.58% accuracy (90.32% for normal villi, 70.59% for VA and 84.21% for CH, sensitivity: 0.84 specificity: 0.92), while the quadratic analysis achieves a final accuracy of 94.03% (96.77% accuracy for normal villi, 94.12% for VA and 89.47% for CH, sensitivity: 0.89, specificity: 0.98).

  3. Serologic evaluation of celiac disease in patients with beta thalassemia major and control

    PubMed Central

    Shahramian, Iraj; Dehghani, Seyed Mohsen; Haghighat, Mahmood; Noori, Noor Mohammad; Teimouri, Ali Reza; Sharafi, Elham; Kalili, Manijeh

    2015-01-01

    Aim: This study reports evaluated prevalence of CD in patients with Beta-thalassemia major. Background: Celiac Disease (CD) is an autoimmune disorder triggered by ingestion of gluten in genetically predisposed individuals. Patients and methods: In this case-control study in a period of 3 years, which was performed on 620 children in two groups of Beta-thalassemia major patients (n=200) and control (n=420), serum tissue transglutamianse (tTG) IgA levels were measured. The two groups were compared together in terms of tTG IgA levels, and p<0.05 was considered significant. Results: The means of serum tTG IgA levels in patients with Beta-thalassemia major and control groups were 28.81±68.44 and 6.94±6.68 U/mL, respectively. There was a significant difference in favor of the case group (p=0.000). Body mass index in the two case and control groups had a significant difference (t=3.859, p=0.001). Belonging to each group will change the probability of having less than 20 in tTG IgA (odds=0.285) and it means that belonging to the control group has a protective role. There is only a significant association in the case of all population (r=0.102, p=0.011). Body mass index in the two case and control groups had a significant difference (t=3.859, p=0.001). Conclusion: Probability of CD should be considered since the prevalence of CD is high in patients with and Beta-thalassemia major. Patients with thalassemia major are recommended for screening for CD. PMID:25926941

  4. An electrochemical immunoassay for the screening of celiac disease in saliva samples.

    PubMed

    Adornetto, Gianluca; Fabiani, Laura; Volpe, Giulia; De Stefano, Alessia; Martini, Sonia; Nenna, Raffaella; Lucantoni, Federica; Bonamico, Margherita; Tiberti, Claudio; Moscone, Danila

    2015-09-01

    A highly sensitive electrochemical immunoassay for the initial diagnosis of celiac disease (CD) in saliva samples that overcomes the problems related to its high viscosity and to the low concentration of anti-transglutaminase antigen (tTG) IgA in this medium has been developed for the first time. The system uses magnetic beads (MBs) covered with tTG, which reacts with the anti-tTG IgA antibodies present in positive saliva samples. An anti-human IgA, conjugated with alkaline phosphate (AP) enzyme, was used as the label and a strip of eight magnetized screen-printed electrodes as the electrochemical transducer. In particular, two different immunoassay approaches were optimized and blindly compared to analyze a large number of saliva samples, whose anti-tTG IgA levels were independently determined by the radioimmunoassay (RIA) method. The obtained results, expressed as Ab index, were used to perform a diagnostic test evaluation through the construction of receiver operating characteristic (ROC) curves. The approach, involving a pre-incubation between the anti-human IgA-AP and saliva samples prior to the addition of MBs-tTG, showed a cutoff of 0.022 with 95% clinical sensitivity and 96% clinical specificity. The area under the ROC curve is equal to 1, a result that classifies our test as "perfect." This study demonstrates that it is possible to perform the screening of CD with a rapid, simple, inexpensive, and sensitive method able to detect anti-tTG antibodies in saliva samples, which are easily obtained by non-invasive techniques. This aspect is of fundamental importance to screen a large number of subjects, especially in the pediatric age.

  5. 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

  6. 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.

  7. Improving the Estimation of Celiac Disease Sibling Risk by Non-HLA Genes

    PubMed Central

    Izzo, Valentina; Pinelli, Michele; Tinto, Nadia; Esposito, Maria Valeria; Cola, Arturo; Sperandeo, Maria Pia; Tucci, Francesca; Cocozza, Sergio; Greco, Luigi; Sacchetti, Lucia

    2011-01-01

    Celiac Disease (CD) is a polygenic trait, and HLA genes explain less than half of the genetic variation. Through large GWAs more than 40 associated non-HLA genes were identified, but they give a small contribution to the heritability of the disease. The aim of this study is to improve the estimate of the CD risk in siblings, by adding to HLA a small set of non-HLA genes. One-hundred fifty-seven Italian families with a confirmed CD case and at least one other sib and both parents were recruited. Among 249 sibs, 29 developed CD in a 6 year follow-up period. All individuals were typed for HLA and 10 SNPs in non-HLA genes: CCR1/CCR3 (rs6441961), IL12A/SCHIP1 and IL12A (rs17810546 and rs9811792), TAGAP (rs1738074), RGS1 (rs2816316), LPP (rs1464510), OLIG3 (rs2327832), REL (rs842647), IL2/IL21 (rs6822844), SH2B3 (rs3184504). Three associated SNPs (in LPP, REL, and RGS1 genes) were identified through the Transmission Disequilibrium Test and a Bayesian approach was used to assign a score (BS) to each detected HLA+SNPs genotype combination. We then classified CD sibs as at low or at high risk if their BS was respectively < or ≥ median BS value within each HLA risk group. A larger number (72%) of CD sibs showed a BS ≥ the median value and had a more than two fold higher OR than CD sibs with a BS value < the median (O.R = 2.53, p = 0.047). Our HLA+SNPs genotype classification, showed both a higher predictive negative value (95% vs 91%) and diagnostic sensitivity (79% vs 45%) than the HLA only. In conclusion, the estimate of the CD risk by HLA+SNPs approach, even if not applicable to prevention, could be a precious tool to improve the prediction of the disease in a cohort of first degree relatives, particularly in the low HLA risk groups. PMID:22087237

  8. The prevalence of abnormal celiac antibodies and celiac disease in patients with suspected irritable bowel syndrome: a prospective multi-center US study

    PubMed Central

    Cash, Brooks D.; Rubenstein, Joel H.; Young, Patrick E.; Gentry, Andrew; Nojkov, Borko; Lee, Dong; Andrews, A. Hirsohi; Dobhan, Richard; Chey, William D.

    2011-01-01

    Background & Aims Guidelines recommend that patients with symptoms of non-constipated inflammatory bowel syndrome (NC-IBS) undergo testing for celiac disease (CD). We evaluated the prevalence of CD antibodies and biopsy confirmed CD among patients with NC-IBS in a large US population. Methods In a study conducted at 4 sites, from 2003 to 2008, we compared data from 492 patients with symptoms of NC-IBS to 458 asymptomatic individuals who underwent colonoscopy examinations for cancer screening or polyp surveillance (controls). All participants provided blood samples for specific and non-specific CD-associated antibodies. Additionally, patients with IBS were analyzed for complete blood cell counts, metabolic factors, erythrocyte sedimentation rates, and levels of C-reactive protein and thyroid-stimulating hormone. Any subjects found to have CD-associated antibodies were offered esophagogastroduodenoscopy and duodenal biopsy analysis. Results Of patients with NC-IBS, 7.3% had abnormal results in tests for CD-associated antibodies, compared to 4.8% of controls (adjusted odds ratio=1.49; 95% confidence interval, 0.76–2.90. P=.25). Within the NC-IBS group, 6.51% had antibodies against gliadin, 1.22% against tissue transglutaminase, and 0.61% against endomysium (P>.05 vs controls for all antibodies tested). CD was confirmed in 0.41% of patients in the NC-IBS group and 0.44% of controls (P>0.99). Conclusions Although CD-associated antibodies are relatively common, the prevalence of CD among patients with NC-IBS is similar to that among controls in a large US population. These findings challenge recommendations to routinely screen patients with NC-IBS for CD. More than 7% of patients with NC-IBS had CD-associated antibodies, indicating that gluten sensitivity might mediate IBS symptoms; further studies are needed. PMID:21762658

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

    PubMed Central

    2011-01-01

    Background Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders. Methods CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity. Results Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293). Conclusions This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function. PMID:21392369

  10. Increased production of interleukin-21, but not interleukin-17A, in the small intestine characterizes pediatric celiac disease.

    PubMed

    van Leeuwen, M A; Lindenbergh-Kortleve, D J; Raatgeep, H C; de Ruiter, L F; de Krijger, R R; Groeneweg, M; Escher, J C; Samsom, J N

    2013-11-01

    Celiac disease (CD) is caused by inflammatory CD4(+) T-cell responses to dietary gluten. It is unclear whether interleukin (IL)-21 and IL-17A contribute to CD onset and lesion severity; therefore, we investigated IL-21 and IL-17A expression in biopsies from pediatric CD patients with different histopathological scores. High numbers of IL-21-producing cells were observed in pediatric CD lesions, even Marsh 1-2 lesions, whereas increased numbers of IL-17 secreting cells were not observed. Intraepithelial lymphocytes, CD4(+) T cells and also neutrophils secreted IL-21. Flow cytometry of lamina propria cells revealed a large population of IL-21- and interferon-γ (IFN-γ)-secreting CD3(+) T cells that did not secrete IL-17A. Adult CD patient biopsies also contained high numbers of IL-21-positive cells; however, enhanced numbers of IL-17-positive cells were observed in a small subgroup of patients with severe lesions. As duodenal tissue damage increases contact with microbe-associated molecular patterns, we hypothesized that microbial sensing by Toll-like receptors (TLRs) modulates T cell-derived cytokine secretion. Costimulation with TLR3 ligands during polyclonal T-cell activation significantly increased IL-21 secretion, whereas TLR2 ligands selectively enhanced IL-17A. These results demonstrate that an IL-17A-independent increase in IL-21 production by CD4(+) T cells is characteristic of pediatric CD. We hypothesize that incidental IL-17 secretion is caused by tissue damage rather than gluten-specific responses.

  11. Interferon-gamma released by gluten-stimulated celiac disease-specific intestinal T cells enhances the transepithelial flux of gluten peptides.

    PubMed

    Bethune, Michael T; Siegel, Matthew; Howles-Banerji, Samuel; Khosla, Chaitan

    2009-05-01

    Celiac sprue is a T-cell-mediated enteropathy elicited in genetically susceptible individuals by dietary gluten proteins. To initiate and propagate inflammation, proteolytically resistant gluten peptides must be translocated across the small intestinal epithelium and presented to DQ2-restricted T cells, but the effectors enabling this translocation under normal and inflammatory conditions are not well understood. We demonstrate that a fluorescently labeled antigenic 33-mer gluten peptide is translocated intact across a T84 cultured epithelial cell monolayer and that preincubation of the monolayer with media from gluten-stimulated, celiac patient-derived intestinal T cells enhances the apical-to-basolateral flux of this peptide in a dose-dependent, saturable manner. The permeability-enhancing activity of activated T-cell media is inhibited by blocking antibodies against either interferon-gamma or its receptor and is recapitulated using recombinant interferon-gamma. At saturating levels of interferon-gamma, activated T-cell media does not further increase transepithelial peptide flux, indicating the primacy of interferon-gamma as an effector of increased epithelial permeability during inflammation. Reducing the assay temperature to 4 degrees C reverses the effect of interferon-gamma but does not reduce basal peptide flux occurring in the absence of interferon-gamma, suggesting active transcellular transport of intact peptides is increased during inflammation. A panel of disease-relevant gluten peptides exhibited an inverse correlation between size and transepithelial flux but no apparent sequence constraints. Anti-interferon-gamma therapy may mitigate the vicious cycle of gluten-induced interferon-gamma secretion and interferon-gamma-mediated enhancement of gluten peptide flux but is unlikely to prevent translocation of gluten peptides in the absence of inflammatory conditions.

  12. Association between the MYO9B polymorphisms and celiac disease risk: a meta-analysis

    PubMed Central

    Liao, Ning; Chen, Min-Li; Zhao, Hua; Xie, Zheng-Fu

    2015-01-01

    Background: There is no consensus regarding the association between polymorphisms in the myosin IXB (MYO9B) gene and celiac disease (CD) risk. In this study, we performed a meta-analysis to evaluate genetic variants in MYO9B with CD. Methods: Four MYO9B polymorphisms (rs1545620, rs1457092, rs2305767 and rs2305764) were assessed. A literature search was conducted using PubMed, Scopus, and Web of Science databases until June 2015. Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association under dominant, recessive, homozygote and allelic comparison models. Results: Seven case-control studies with a total of 1965 CD patients and 4894 controls were included in this meta-analysis. The results showed that rs1545620 was associated with CD risk in Europeans in dominant (OR=1.31, 95% CI: 1.10-1.58, Pz=0.003), recessive (OR=1.36, 95% CI: 1.08-1.72, Pz=0.009), homozygote (OR=1.55, 95% CI: 1.20-2.01, Pz=0.001), and allelic comparison models (OR=1.24, 95% CI: 1.10-1.40, Pz=0.001), whereas in a Latin American group there were significant associations of CD with rs1457092 in dominant (OR=15.30, 95% CI: 3.51-66.67, Pz<0.001), homozygote (OR=16.55, 95% CI: 3.62-75.65, Pz<0.001), and allelic comparison models (OR=1.95, 95% CI: 1.31-2.91, Pz=0.001), and rs2305767 in dominant (OR=5.35, 95% CI: 2.42-11.86, Pz<0.001) and allelic comparison models (OR=1.65, 95% CI: 1.11-2.45, Pz=0.013). There was no association between rs2305764 and CD risk in either Europeans or the Latin American group. Conclusion: rs1545620 is associated with CD risk in Europeans, whereas rs1457092 and rs2305767 are associated with CD risk in a Latin American group. PMID:26628973

  13. Seroprevalence of celiac disease among United Arab Emirates healthy adult nationals: A gender disparity

    PubMed Central

    Abu-Zeid, Yousif A; Jasem, Waheeba S; Lebwohl, Benjamin; Green, Peter H; ElGhazali, Gehad

    2014-01-01

    AIM: To determine celiac disease (CD) prevalence and associated manifestations or risk factors in healthy adult Emiratis. METHODS: It is a cross-sectional prospective study, recruiting 1197 (573 women and 624 men) healthy Emiratis between September 2007 and April 2008 among those who went to Al Ain Hospital to undertake the prenuptial examination. Test for anti-tissue transglutaminase (tTG) IgA antibodies was used for CD diagnosis. Subjects with positive results in the anti tTG antibodies assay were also tested for anti-endomysial (EMA) IgA antibodies. A structured interview was used to collect basic demographic and clinical recall data including: information on name, contact address, age, gender, education status, previous diagnosis of CD, diagnosis of CD in 1st degree relatives and history of “chronic diarrhea, anemia, headache, hepatitis, diabetes, tumor, and thyroid disorder”. RESULTS: Fourteen blood samples (1.17%; 14/1197) were seropositive for CD. The latent CD seropositive patients were 13 women and 1 man and therefore the seroprevalence of CD was 1:86 (14/1197) for adult Emiratis: 1:44 (13/573) for women and 1:624 for men. Binary logistic regression revealed that history of chronic anemia (crude OR = 7.09; 95%CI: 2.32-21.61; P = 0.003) and being a woman (OR = 14.46; 95%CI: 1.89-110.91; P = 0.001) were associated with CD seropositivity. Whereas, the thyroid disorder showed a positive association with CD seropositivity that approach statistical significance (OR = 11.30; 95%CI: 1.32-96.95; P = 0.09) and therefore was included in the multiple logistic regression analysis, which showed that CD seropositivity is independently associated only with history of chronic anemia (OR = 4.58; 95%CI: 1.45-14.48; P = 0.01) and being a woman person (OR = 10.47; 95%CI: 1.33-82.14; P = 0.026). CONCLUSION: Compared to men the CD seroprevalence among women was remarkably higher. The CD association with women and chronic anemia is of importance from a public health

  14. Evaluation of the Correlation Between tTG-IgA Titer and Duodenal Biopsy Findings in Children With Suspected Celiac Disease

    PubMed Central

    Aldaghi, Mitra-Azra; Dehghani, Seyed-Mohsen; Haghighat, Mahmood

    2016-01-01

    Background: Celiac disease is an immune-mediated inflammation of the small intestine caused by sensitivity to dietary gluten in genetically sensitive individuals. Objectives: In this study, we aimed to evaluate the predictive value of tissue transglutaminase (tTG) antibodies for the diagnosis of celiac disease in a pediatric population in order to determine if duodenal biopsy can be avoided. Patients and Methods: The subjects were selected among individuals with probable celiac disease, referring to a gastrointestinal clinic. After physical examinations and performing tissue transglutaminase-immunoglobulin A (tTG-IgA) tests, upper endoscopy was performed if serological titer was higher than 18 IU/mL. Therapy started according to pathologic results. Results: The sample size was calculated to be 121 subjects (69 female and 52 male subjects); the average age of subjects was 8.4 years. A significant association was found between serological titer and pathologic results; in other words, subjects with high serological titer had more positive pathologic results for celiac disease, compared to others (P < 0.001). Maximum sensitivity (65%) and specificity (65.4%) were achieved at a serological titer of 81.95 IU/ml; the calculated accuracy was lower in comparison with other studies. As the results indicated, lower antibody titer was observed in patients with failure to gain weight and higher antibody titer was reported in diabetic patients. Conclusions: As the results indicated, a single serological test (tTg-IgA test) was not sufficient for avoiding intestinal biopsy. PMID:26848375

  15. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. A Case of Autoimmune Polyglandular Syndrome (APS) Type II with Hypothyroidism, Hypoadrenalism, and Celiac Disease - A Rare Combination.

    PubMed

    Lakhotia, Manoj; Pahadia, Hans Raj; Kumar, Harish; Singh, Jagdish; Tak, Sandeep

    2015-04-01

    Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison's disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison's disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison's disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon.

  17. A combined biochemical, biophysical and immunological approach towards the identification of celiac disease-specific wheat antigens.

    PubMed

    Srinivasan, Bharani; Focke-Tejkl, Margarete; Swoboda, Ines; Constantin, Claudia; Mittermann, Irene; Pahr, Sandra; Vogelsang, Harald; Huber, Wolf-Dietrich; Valenta, Rudolf

    2013-10-01

    Celiac disease (CD) is an inflammatory affliction of the small bowel caused by an immunological hypersensitivity to ingested wheat antigens affecting almost 1 % of the population. The gliadin fraction of wheat has been shown to contain the pathogenic antigens which react with antibodies and T cells. However, there is only limited knowledge regarding the precise nature of the wheat antigens recognized by IgA antibodies from CD patients and diagnostic tests based on the gliadin fraction have been demonstrated to give frequently false positive results. The aim of this study was the characterization of wheat antigens specifically recognized by IgA antibodies of CD patients. We developed a combined biochemical, biophysical, and immunological approach for the identification of celiac disease-specific wheat antigens. It is based on sub-fractionation of the wheat gliadin fraction using two ion exchange chromatography steps, the localization of CD-specific antigens by immunoblotting with IgA antibodies from CD patients, subsequent digestion followed by electro spray ionization-liquid chromatography/mass spectrometry (LC-ESI-MS/MS) and N-terminal sequencing by Edman degradation. Through the sub-fractionation procedure it was possible to separate CD-specific IgA-reactive wheat antigens from other wheat antigens which were also recognized by IgA antibodies of individuals without CD or by CD patients on gluten-free diet. Analysis by LC-ESI-MS/MS and N-terminal sequencing of the sub-fractions and the proteins specifically recognized by CD patients identified certain γ-gliadins with molecular mass of 37,000 and 45,000 as CD-specific wheat antigens. The CD-specific γ-gliadins with the molecular mass of 37,000 and 45,000 should be useful to study pathomechanisms of the disease and to improve the specificity of diagnostic tests for CD.

  18. [Connective tissue dysplasia in patients with celiac desease as a problem of violation of adaptation reserve islands of the body].

    PubMed

    Tkachenko, E; Oreshko, L S; Soloveva, E A; Shabanova, A A; Zhuravleva, M S

    2015-01-01

    Clinically significant dysplasia of connective tissue in patients with celiac disease is often responsible for various visceral disorders. Different disturbances of motor and evacuation functions are often determined in this patients (gastroesophageal reflux, duodenogastral reflux, spastic and hyperkinetic dyskinesia). The clinical course of the celiac disease, associated with connective tissue dysplasia, is characterized by asthenovegetative syndrome, reduced tolerance to physical activity, general weakness, fatigue and emotional instability. These data should be considered in choosing a treatment. PMID:25993866

  19. Celiac artery disease and fatal rupture of a hepatic artery aneurysm in the Ehlers-Danlos syndrome.

    PubMed

    Nat, Amritpal; George, Tanya; Mak, Gregory; Sharma, Amit; Nat, Amitpal; Lebel, Robert

    2014-04-01

    Isolated visceral arteriopathies of the celiac and hepatic artery are rare. We present a case of a Caucasian man who presented with abdominal pain and was found to have a spontaneous celiac artery dissection. Genetic analysis revealed a mutation consistent with Ehlers-Danlos syndrome type IV. The patient died 2 months later from a spontaneous rupture of his hepatic artery. PMID:24688192

  20. The distribution of DQ genes in the Saharawi population provides only a partial explanation for the high celiac disease prevalence.

    PubMed

    Catassi, C; Doloretta Macis, M; Rätsch, I M; De Virgiliis, S; Cucca, F

    2001-12-01

    Celiac disease (CD) is a multifactorial disorder of the small intestine caused by a permanent dietary intolerance to gluten. The combined presence of the HLA class II DQA1*0501 and DQB1*0201 alleles represents the major genetic component for disease predisposition. It has been shown that the Saharawi refugees living in northern Africa have a very high frequency of CD. In the present study we analysed this population to evaluate the degree of association with CD of the haplotypes and genotypes at the main HLA-DQB1 and DQA1 disease loci. We found a strong association of the DR3, DQB1*0201-DQA1*0501-positive haplotypes and genotypes. A very high frequency of DR3, DQB1*0201-DQA1*0501 was also observed in the general Saharawi population. These results indicate that there is a good correlation between disease prevalence and frequency of the main predisposing haplotype in the background population. However, the correlation is incomplete because similar frequencies of DR3 are also observed in populations such as the Sardinians showing a much lower prevalence of CD. We can conclude that the distribution of DQ genes in the Saharawi population only provides a partial explanation for the high prevalence of CD. Other factors, such as rapidly changing dietary habits and/or non-DQ genes, may also play some role. PMID:11929591

  1. Palaeodiet reconstruction in a woman with probable celiac disease: a stable isotope analysis of bone remains from the archaeological site of Cosa (Italy).

    PubMed

    Scorrano, Gabriele; Brilli, Mauro; Martínez-Labarga, Cristina; Giustini, Francesca; Pacciani, Elsa; Chilleri, Filberto; Scaldaferri, Franco; Gasbarrini, Antonio; Gasbarrini, Giovanni; Rickards, Olga

    2014-07-01

    Stable isotope analysis in the reconstruction of human palaeodiets can yield clues to early human subsistence strategies, origins and history of farming and pastoralist societies, and intra- and intergroup social differentiation. In the last 10 years, the method has been extended to the pathological investigation. Stable isotope analysis to better understand a diet-related disease: celiac disease in ancient human bones was carried out. To do this, we analyzed the nitrogen and carbon isotopic composition of human (n = 37) and faunal (n = 8) bone remains from the archaeological site of Cosa at Ansedonia, on the Tyrrhenian coast near Orbetello (Tuscany), including the skeletal remains of a young woman (late 1st century-early 2nd century Common Era [CE]) with morphological and genetic features suggestive of celiac disease. We compared the young woman's isotopic data with those of other individuals recovered at the same site but from two later time periods (6th century CE; 11-12th century CE) and with literature data from other Italian archaeological sites dating to the same period. Her collagen δ(13) C and δ(15) N values differed from those of the samples at the same site, and from most but not all of the contemporary sites. Although the woman's diet appears distinct, chronic malnutrition resulting from severe malabsorption of essential nutrients due to celiac disease may have affected the isotopic composition of her bone collagen. PMID:24706415

  2. Palaeodiet reconstruction in a woman with probable celiac disease: a stable isotope analysis of bone remains from the archaeological site of Cosa (Italy).

    PubMed

    Scorrano, Gabriele; Brilli, Mauro; Martínez-Labarga, Cristina; Giustini, Francesca; Pacciani, Elsa; Chilleri, Filberto; Scaldaferri, Franco; Gasbarrini, Antonio; Gasbarrini, Giovanni; Rickards, Olga

    2014-07-01

    Stable isotope analysis in the reconstruction of human palaeodiets can yield clues to early human subsistence strategies, origins and history of farming and pastoralist societies, and intra- and intergroup social differentiation. In the last 10 years, the method has been extended to the pathological investigation. Stable isotope analysis to better understand a diet-related disease: celiac disease in ancient human bones was carried out. To do this, we analyzed the nitrogen and carbon isotopic composition of human (n = 37) and faunal (n = 8) bone remains from the archaeological site of Cosa at Ansedonia, on the Tyrrhenian coast near Orbetello (Tuscany), including the skeletal remains of a young woman (late 1st century-early 2nd century Common Era [CE]) with morphological and genetic features suggestive of celiac disease. We compared the young woman's isotopic data with those of other individuals recovered at the same site but from two later time periods (6th century CE; 11-12th century CE) and with literature data from other Italian archaeological sites dating to the same period. Her collagen δ(13) C and δ(15) N values differed from those of the samples at the same site, and from most but not all of the contemporary sites. Although the woman's diet appears distinct, chronic malnutrition resulting from severe malabsorption of essential nutrients due to celiac disease may have affected the isotopic composition of her bone collagen.

  3. Distal Pancreatectomy With En Bloc Resection of the Celiac Trunk for Extended Pancreatic Tumor Disease: An Interdisciplinary Approach

    SciTech Connect

    Denecke, Timm; Andreou, Andreas; Podrabsky, Petr; Grieser, Christian; Warnick, Peter; Bahra, Marcus; Klein, Fritz; Hamm, Bernd; Neuhaus, Peter; Glanemann, Matthias

    2011-10-15

    Purpose: Infiltration of the celiac trunk by adenocarcinoma of the pancreatic body has been considered a contraindication for surgical treatment, thus resulting in a very poor prognosis. The concept of distal pancreatectomy with resection of the celiac trunk offers a curative treatment option but implies the risk of relevant hepatic or gastric ischemia. We describe initial experiences in a small series of patients with left celiacopancreatectomy with or without angiographic preconditioning of arterial blood flow to the stomach and the liver. Materials and Methods: Between January 2007 and October 2009, six patients underwent simultaneous resection of the celiac trunk for adenocarcinoma of the pancreatic body involving the celiac axis. In four of these cases, angiographic occlusion of the celiac trunk before surgery was performed to enhance collateral flow from the gastroduodenal artery. Radiologic and surgical procedures, findings, and outcome were analyzed retrospectively. Results: Complete tumor removal (R0) succeeded in two patients, whereas four patients underwent R1-tumor resection. After surgery, one of the two patients without angiographic preparation experienced an ischemic stomach perforation 1 week after surgery. The other patient died from severe bleeding from an ischemic gastric ulcer. Of the four patients with celiac trunk embolization, none presented ischemic complications after surgery. Mean survival was 371 days. Conclusion: In this small series, ischemic complications after celiacopancreatectomy occurred only in those patients who did not receive preoperative celiac trunk embolization.

  4. Celiac Disease in Patients Fulfilling the Rome III Criteria for Irritable Bowel Syndrome Attending Gastroenterology Department of A Tertiary Care Hospital in Bangladesh.

    PubMed

    Chowdhury, M K; Chakraborty, R; Gope, S; Rahman, M A; Miah, A R; Raihan, A S; Sarkar, S; Paul, B K; Ferdousi, K R

    2016-01-01

    Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that substantially affects patients' quality of life and is associated with a considerable drain of health-care resources and economic burden. But some IBS patients may have celiac disease that could be treated by gluten-free diet which will subsequently improve their quality of life. This study was done to see the prevalence of celiac disease among the IBS patients fulfilling Rome III criteria. The present cross-sectional study was conducted in the Department of Gastroenterology at BSMMU, Dhaka from July 2010 to September 2011. A total of 107 patients aged ranging between 16-60 years clinically labeled as IBS and fulfilled Rome III criteria were included as study sample. The test statistics used to analyze the data were descriptive statistics. The mean age of the patients was 31.5±10.3 years and male to female ratio was roughly 6:1. The mean duration of IBS was 32.0±2.1 months. All of the patients had abdominal discomfort or pain in the preceding 6 months and had a history of loose (mushy) or watery stool, 99.1% had pain or discomfort relieved with defaecation. The prevalence of diarrhoea was found in 78.5% and mixed 21.5% of the patients. About 5% of the patients had raised ESR and majority (86.9%) of the patients had normal level of hemoglobin. Ten (9%) of 107 patients were found positive for anti-t TG (IgA). These findings suggest that an around one-tenth of IBS especially diarrhoea predominant patients may have celiac disease who will respond to simple gluten-free diet thus minimizing the morbidity and mortality. So, all clinically diagnosed IBS patients especially diarrhoea predominant cases should be suggested for the screening for celiac disease. PMID:26931258

  5. Celiac Disease in Patients Fulfilling the Rome III Criteria for Irritable Bowel Syndrome Attending Gastroenterology Department of A Tertiary Care Hospital in Bangladesh.

    PubMed

    Chowdhury, M K; Chakraborty, R; Gope, S; Rahman, M A; Miah, A R; Raihan, A S; Sarkar, S; Paul, B K; Ferdousi, K R

    2016-01-01

    Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that substantially affects patients' quality of life and is associated with a considerable drain of health-care resources and economic burden. But some IBS patients may have celiac disease that could be treated by gluten-free diet which will subsequently improve their quality of life. This study was done to see the prevalence of celiac disease among the IBS patients fulfilling Rome III criteria. The present cross-sectional study was conducted in the Department of Gastroenterology at BSMMU, Dhaka from July 2010 to September 2011. A total of 107 patients aged ranging between 16-60 years clinically labeled as IBS and fulfilled Rome III criteria were included as study sample. The test statistics used to analyze the data were descriptive statistics. The mean age of the patients was 31.5±10.3 years and male to female ratio was roughly 6:1. The mean duration of IBS was 32.0±2.1 months. All of the patients had abdominal discomfort or pain in the preceding 6 months and had a history of loose (mushy) or watery stool, 99.1% had pain or discomfort relieved with defaecation. The prevalence of diarrhoea was found in 78.5% and mixed 21.5% of the patients. About 5% of the patients had raised ESR and majority (86.9%) of the patients had normal level of hemoglobin. Ten (9%) of 107 patients were found positive for anti-t TG (IgA). These findings suggest that an around one-tenth of IBS especially diarrhoea predominant patients may have celiac disease who will respond to simple gluten-free diet thus minimizing the morbidity and mortality. So, all clinically diagnosed IBS patients especially diarrhoea predominant cases should be suggested for the screening for celiac disease.

  6. Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease

    PubMed Central

    Vangone, Anna; Abdel-Azeim, Safwat; Caputo, Ivana; Sblattero, Daniele; Di Niro, Roberto; Cavallo, Luigi; Oliva, Romina

    2014-01-01

    Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. PMID:25076134

  7. The cannabinoid receptor type 2 Q63R variant increases the risk of celiac disease: implication for a novel molecular biomarker and future therapeutic intervention.

    PubMed

    Rossi, Francesca; Bellini, Giulia; Tolone, Carlo; Luongo, Livio; Mancusi, Silvia; Papparella, Alfonso; Sturgeon, Craig; Fasano, Alessio; Nobili, Bruno; Perrone, Laura; Maione, Sabatino; del Giudice, Emanuele Miraglia

    2012-07-01

    Celiac disease (CD) is a chronic inflammatory disease of the small bowel that occurs with the ingestion of gluten, found in several grains products. Although HLA-DQ2 variant is required for the gluten-derived peptide gliadin presentation by antigen-presenting cells to T-cells, non-HLA genetic factors account for the majority of heritable risk. Several genome-wide association studies have identified susceptibility loci for CD on chromosome 1. Cells of the immune system express the cannabinoid receptor type 2 (CB2), a plasma-membrane receptor activated by both endogenous and exogenous cannabinoids. Consistent data evidence that CB2 is linked to a variety of immune functional events and that, in the course of an inflammatory process, an increased number of receptors becomes available for activation. The cannabinoid receptor type 2 gene (CNR2; GeneID1269) maps on 1p36.11. In order to investigate the possible involvement of CB2 in CD establishment, immunohistochemistry toward CB2 receptor and CD4+ cells in small bowel biopsies from celiac children and association analysis, through TaqMan assay, of a CNR2 common missense variant, rs35761398 (CAA/CGG), resulting in the aminoacidic substitution of Glutamine at codon 63 with Arginine (Q63R), in a cohort of 327 South Italian children have been performed. We observed in this study that CB2 is up-regulated in CD small bowel biopsies and CNR2 rs35761398 is significantly associated with CD (χ(2) = 37.064; d.f. 1; p = 1.14 × 10(-9)). Our findings suggest a role of CB2 in CD. The Q63R variant, increasing more than six-fold the risk for CD susceptibility, might eventually represent a novel molecular biomarker for CD risk stratification. Indeed, we provide here further evidence that CB2 receptor plays a critical role in autoimmunity susceptibility and indicates that it represents a molecular target to pharmacologically modulate the immune components in CD.

  8. The role of soluble tumor necrosis factor like weak inducer of apoptosis and interleukin-17A in the etiopathogenesis of celiac disease: A cross-sectional study.

    PubMed

    Yuksel, Mahmut; Kaplan, Mustafa; Ates, Ihsan; Kilic, Zeki Mesut Yaln; Kilic, Hasan; Suna, Nuretdin; Ates, Hale; Kayacetin, Ertugrul

    2016-06-01

    Our aim in this study was to determine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in celiac disease, and their association with the gluten diet and autoantibodies. Eighty patients with celiac diagnosis and 80 healthy control individuals with similar age, gender and body mass index to the patient group were included in the study. Serum sTWEAK and IL-17A levels were measured by the serum enzyme-linked immunosorbent assay kit. The median IL-17A (117.5 pg/mL vs. 56.7 pg/mL; P = 0.001) level in celiac patients was higher than in the control group, while the median sTWEAK (543 pg/mL vs. 643 pg/mL; P = 0.016) level in patients was determined to be lower. In the patient group, patients who complied with the gluten diet had a lower level of median IL-17A (98.1 pg/mL vs. 197.5 pg/mL; P = 0.034) and a higher level of sTWEAK (606 pg/mL vs. 522.8 pg/mL; P = 0.031) than those who did not adhere. Furthermore, the IL-17A level was higher and the sTWEAK level was lower in celiac patients with positive antibody than those with negative antibody. A positive correlation was determined among anti-gliadin antibody IgA, anti-gliadin antibody IgG, anti-tissue transglutaminase IgG levels and the IL-17A level, and a negative correlation was determined with the sTWEAK level. In celiac disease, the sTWEAK and IL-17A levels differ between patients who cannot adapt to the gluten diet and who are autoantibody positive, and patients who adapt to the diet and are autoantibody negative. We believe that sTWEAK and IL-17A are associated with the inflammation in celiac pathogenesis. PMID:27367991

  9. The role of soluble tumor necrosis factor like weak inducer of apoptosis and interleukin-17A in the etiopathogenesis of celiac disease

    PubMed Central

    Yuksel, Mahmut; Kaplan, Mustafa; Ates, Ihsan; Kilic, Zeki Mesut Yalın; Kilic, Hasan; Suna, Nuretdin; Ates, Hale; Kayacetin, Ertugrul

    2016-01-01

    Abstract Our aim in this study was to determine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in celiac disease, and their association with the gluten diet and autoantibodies. Eighty patients with celiac diagnosis and 80 healthy control individuals with similar age, gender and body mass index to the patient group were included in the study. Serum sTWEAK and IL-17A levels were measured by the serum enzyme-linked immunosorbent assay kit. The median IL-17A (117.5 pg/mL vs. 56.7 pg/mL; P = 0.001) level in celiac patients was higher than in the control group, while the median sTWEAK (543 pg/mL vs. 643 pg/mL; P = 0.016) level in patients was determined to be lower. In the patient group, patients who complied with the gluten diet had a lower level of median IL-17A (98.1 pg/mL vs. 197.5 pg/mL; P = 0.034) and a higher level of sTWEAK (606 pg/mL vs. 522.8 pg/mL; P = 0.031) than those who did not adhere. Furthermore, the IL-17A level was higher and the sTWEAK level was lower in celiac patients with positive antibody than those with negative antibody. A positive correlation was determined among anti-gliadin antibody IgA, anti-gliadin antibody IgG, anti-tissue transglutaminase IgG levels and the IL-17A level, and a negative correlation was determined with the sTWEAK level. In celiac disease, the sTWEAK and IL-17A levels differ between patients who cannot adapt to the gluten diet and who are autoantibody positive, and patients who adapt to the diet and are autoantibody negative. We believe that sTWEAK and IL-17A are associated with the inflammation in celiac pathogenesis. PMID:27367991

  10. Patients With Celiac Disease and B-Cell Lymphoma Have a Better Prognosis Than Those With T-Cell Lymphoma

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubio–Tapia, Alberto; Ristow, Kay M.; Habermann, Thomas M.; Murray, Joseph A.; Inwards, David J.

    2013-01-01

    Background & Aims Celiac disease (CD) is associated with an increased risk of lymphoma. However, relatively few studies have assessed the outcome of patients diagnosed with both CD and lymphoma. We evaluated the temporal association between lymphoma and CD, along with clinical presentation, response to therapy, and prognosis. Methods Patients diagnosed with both CD and lymphoma were identified retrospectively in a tertiary referral center. Clinical characteristics and survival were analyzed. Results Sixty-three patients (36 men) were identified who had been diagnosed with lymphoma and CD. Thirty-six (57%) were diagnosed with CD before they were diagnosed with lymphoma. The most common histologic entity was diffuse, large, B-cell lymphoma, which affected 18 (29%) patients. Complete information for staging was available in 59 patients; 24 (38%) had stage IV disease. Only chemotherapy or only radiation therapy was used for 43 (68%) and 11 (17%) patients, respectively. The 5- and 10-year cumulative survival rates for the entire cohort were 58% and 39%, respectively. Survival of patients with T-cell lymphoma was shorter than for all other lymphomas (119.4 vs 22.8 mo; P = .02). Conclusions CD is associated with B- and T-cell lymphomas. Patients with B-cell lymphomas had a better prognosis than those with T-cell lymphoma. Therapy is unsatisfactory for enteropathy-type T-cell lymphoma. PMID:20851210

  11. Mucosal Molecular Pattern of Tissue Transglutaminase and Interferon Gamma in Suspected Seronegative Celiac Disease at Marsh 1 and 0 Stages

    PubMed Central

    Ierardi, Enzo; Amoruso, Annacinzia; Giorgio, Floriana; Principi, Mariabeatrice; Losurdo, Giuseppe; Piscitelli, Domenico; Buffelli, Francesca; Fiore, Maria G.; Mongelli, Antonio; Castellaneta, Nicola M.; Giangaspero, Antonio; De Francesco, Vincenzo; Montenegro, Lucia; Di Leo, Alfredo

    2015-01-01

    Background/Aim: In celiac disease (CD), there is increased mRNA coding for tissue transglutaminase (tTG) and interferon gamma (IFNγ). In seronegative celiac patients, the mucosal immune complexes anti-tTG IgA/tTG are found. We assayed tTG- and IFNγ-mRNA in the mucosa of patients with a clinical suspicion of seronegative CD and correlated the values with intraepithelial CD3 lymphocytes (IELs). Materials and Methods: Distal duodenum specimens from 67 patients were retrieved and re-evaluated for immunohistochemically proven CD3 IELs. Five 10 μm sections were used for the extraction and assay of tTG and IFNγ coding mRNA levels using reverse transcriptase real-time polymerase chain reaction (RT-PCR). Samples from 15 seropositive CD patients and 15 healthy subjects were used as positive and negative controls. Results were expressed as fold-change. Results: Our series was divided into three groups based on IEL count: >25 (14 patients: group A), 15–25 (26 patients: group B), and 0–15 (27 patients: Group C). tTG-mRNA levels were (mean ± SD): CD = 9.8 ± 2.6; group A = 10.04 ± 4.7; group B = 4.99 ± 2.3; group C = 2.26 ± 0.8, controls = 1.04 ± 0.2 (CD = group A > group B > group C = controls). IFNα-mRNA levels were: CD = 13.4 ± 3.6; group A = 7.28 ± 3.6; group B = 4.45 ± 2.9; group C = 2.06 ± 1.21, controls = 1.04 ± 0.4. Conclusions: Our results suggest that tTG- and IFNγmRNA levels are increased in both seropositive and potential seronegative patients with CD, showing a strong correlation with the CD3 IEL count at stage Marsh 1. An increase in both molecules is found even when IELs are in the range 15–25 (Marsh 0), suggesting the possibility of a “gray zone” inhabited by patients which should be closely followed up in gluten-related disorders. PMID:26655133

  12. Antibodies against neo-epitope tTg complexed to gliadin are different and more reliable then anti-tTg for the diagnosis of pediatric celiac disease.

    PubMed

    Lerner, Aaron; Jeremias, Patricia; Neidhöfer, Sandra; Matthias, Torsten

    2016-02-01

    The neo-epitope tTg (tTg-neo) autoantibody, never challenged the anti-tissue transglutaminase (tTg) premiership, recommended by ESPGHAN, for celiac disease (CD) diagnosis. Pediatric CD (PCD), abdominal pains and normal children, normal adults, and rheumatoid arthritis patients, were tested using the following ELISAs detecting IgA, IgG or both IgA and IgG (check): AESKULISA® tTg (tTg; RUO) and AESKULISA® tTg-neo. Higher OD activity was detected for tTg-neo IgA, IgG and IgA+IgG than for tTg. tTg-neo IgA, IgG correlated better with intestinal damage than tTg. The tTg-neo combined IgA+IgG ELISA kit had higher sensitivity and a comparable specificity for the diagnosis of PCD. The drop in the % competition was much higher with the tTg-neo then the tTg antibodies. The false positivity of the tTg was significantly higher than the tTg-neo one. Serological diagnostic performances, reflection of intestinal damage, diverse epitopes and false positivity were better with the tTg-neo.

  13. Tumor necrosis factor-α and interleukin-6 gene polymorphism association with susceptibility to celiac disease in Italian patients.

    PubMed

    de Albuquerque Maranhão, R M; Martins Esteves, F A; Crovella, S; Segat, L; Eleutério Souza, P R

    2015-12-09

    The aim of this research was to study polymorphisms in the genes encoding cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with celiac disease (CD) antigens DQ2 (DQ2-positive) or DQ8 (DQ8-positive). We compared the results with healthy controls to determine whether any of the polymorphisms have a role in susceptibility to CD. A case-control of 192 patients with CD (96 DQ2-positive and 96 DQ8-positive) and 96 healthy controls from northeast Italy were included in the study. Analysis of single nucleotide polymorphisms (SNPs) was carried out using the polymerase chain reaction-restriction fragment length polymorphism method. Significant differences for the TNF-α(-308 G>A) polymorphism were observed when we compared the flowing groups: DQ2-positive with controls [odds ratio (OR) = 0.45, P = 0.0002]; DQ8-positive with controls (OR = 3.55, P < 0.0001); and DQ2-positive with DQ8-positive (OR = 0.12, P < 0.0001). We did not observe a statistically significant association between IL-6 (-174 G>C) polymorphism and CD (P > 0.05). Our results suggest that TNF-α(-308 G>A) polymorphism may play a role in susceptibility to CD in Italian patients.

  14. Variations and classification of toxic epitopes related to celiac disease among α-gliadin genes from four Aegilops genomes.

    PubMed

    Li, Jie; Wang, Shunli; Li, Shanshan; Ge, Pei; Li, Xiaohui; Ma, Wujun; Zeller, F J; Hsam, Sai L K; Yan, Yueming

    2012-07-01

    The α-gliadins are associated with human celiac disease. A total of 23 noninterrupted full open reading frame α-gliadin genes and 19 pseudogenes were cloned and sequenced from C, M, N, and U genomes of four diploid Aegilops species. Sequence comparison of α-gliadin genes from Aegilops and Triticum species demonstrated an existence of extensive allelic variations in Gli-2 loci of the four Aegilops genomes. Specific structural features were found including the compositions and variations of two polyglutamine domains (QI and QII) and four T cell stimulatory toxic epitopes. The mean numbers of glutamine residues in the QI domain in C and N genomes and the QII domain in C, N, and U genomes were much higher than those in Triticum genomes, and the QI domain in C and N genomes and the QII domain in C, M, N, and U genomes displayed greater length variations. Interestingly, the types and numbers of four T cell stimulatory toxic epitopes in α-gliadins from the four Aegilops genomes were significantly less than those from Triticum A, B, D, and their progenitor genomes. Relationships between the structural variations of the two polyglutamine domains and the distributions of four T cell stimulatory toxic epitopes were found, resulting in the α-gliadin genes from the Aegilops and Triticum genomes to be classified into three groups.

  15. Immune response to Hepatitis B vaccine in patients with celiac disease: A systematic review and meta-analysis

    PubMed Central

    Opri, R; Veneri, D; Mengoli, C; Zanoni, G

    2015-01-01

    It is debated whether patients with celiac disease (CD) have non-protective antibody responses to HBV vaccination more frequently than non-affected subjects. To perform a literature review and meta-analysis on protective response to HBV vaccination in CD patients. RCTs and observational controlled studies were eligible. Outcome of interest was an anti-HBs (HBsAb) titer ≥10 IU/L after last vaccine dose. Comparative index was rate ratio (RR). Heterogeneity between studies was addressed and funnel plots were analyzed. Meta-regression models were applied to investigate effect size due to study-specific variables. Twelve retrospective studies on a total of 1,447 participants and 4 prospective studies on 184 subjects were selected. The RR was 0.732 (95% C.I.: 0.664-0.808) and 0.777 (95% C.I.: 0.629-0.960) in the prospective and retrospective studies, respectively. The I2, indicating heterogeneity, was 51.1% in retrospective, 39.8% in prospective studies. Non-protective antibody responses occurred more frequently in patients than controls. Due to limitations in the available studies, additional trials to evaluate post-vaccination HBsAb titer in CD patients are needed. PMID:26378476

  16. Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species.

    PubMed

    Sánchez, Ester; De Palma, Giada; Capilla, Amalia; Nova, Esther; Pozo, Tamara; Castillejo, Gemma; Varea, Vicente; Marcos, Ascensión; Garrote, José Antonio; Polanco, Isabel; López, Ana; Ribes-Koninckx, Carmen; García-Novo, Maria Dolores; Calvo, Carmen; Ortigosa, Luis; Palau, Francesc; Sanz, Yolanda

    2011-08-01

    Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization of Bacteroides species in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). The Bacteroides species diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence of Bacteroides uniformis at 1 and 4 months of age, while formula-fed infants had a higher prevalence of B. intestinalis at all sampling times, of B. caccae at 7 days and 4 months, and of B. plebeius at 4 months. Infants with high genetic risk showed a higher prevalence of B. vulgatus, while those with low genetic risk showed a higher prevalence of B. ovatus, B. plebeius, and B. uniformis. Among breast-fed infants, the prevalence of B. uniformis was higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence of B. ovatus and B. plebeius was increased in those with low genetic risk, while the prevalence of B. vulgatus was higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process of Bacteroides species, and possibly the disease risk.

  17. Influence of Environmental and Genetic Factors Linked to Celiac Disease Risk on Infant Gut Colonization by Bacteroides Species▿

    PubMed Central

    Sánchez, Ester; De Palma, Giada; Capilla, Amalia; Nova, Esther; Pozo, Tamara; Castillejo, Gemma; Varea, Vicente; Marcos, Ascensión; Garrote, José Antonio; Polanco, Isabel; López, Ana; Ribes-Koninckx, Carmen; García-Novo, Maria Dolores; Calvo, Carmen; Ortigosa, Luis; Palau, Francesc; Sanz, Yolanda

    2011-01-01

    Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization of Bacteroides species in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). The Bacteroides species diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence of Bacteroides uniformis at 1 and 4 months of age, while formula-fed infants had a higher prevalence of B. intestinalis at all sampling times, of B. caccae at 7 days and 4 months, and of B. plebeius at 4 months. Infants with high genetic risk showed a higher prevalence of B. vulgatus, while those with low genetic risk showed a higher prevalence of B. ovatus, B. plebeius, and B. uniformis. Among breast-fed infants, the prevalence of B. uniformis was higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence of B. ovatus and B. plebeius was increased in those with low genetic risk, while the prevalence of B. vulgatus was higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process of Bacteroides species, and possibly the disease risk. PMID:21642397

  18. Health-related quality of life in children and adolescents with celiac disease: survey of a population from central Italy

    PubMed Central

    2013-01-01

    Background Celiac Disease (CD) is an increasingly common autoimmune disorder. It requires a strict lifelong adherence to a gluten-free diet (GFD) which can influence health-related quality of life (HRQOL). This study assesses HRQOL in children and adolescents with CD and explores how several demographic and clinical characteristics and GFD adherence affect their perceived health status. Methods We recruited 140 consecutive children and adolescents with CD confirmed by small bowel biopsy. HRQOL was assessed using the SF-12 questionnaire plus some CD-specific questions exploring wellbeing and lifestyle. Patients, aged 10 to 18 years, were identified by pediatric gastroenterologists and guided in filling out the questionnaire by trained psychologists. Parametric or non-parametric tests were applied to analyze continuous variables and frequencies as appropriate. Results The SF-12 mean mental component summary score (MCS12) was lower than in the general Italian population (p < 0.001), whereas differences in terms of physical health were not significant (p = 0.220). More than one third of those interviewed reported feeling angry “always” or “most of the time” about having to follow the GFD, and nearly 20% reported feeling different from others and misunderstood because of CD “always” or “most of the time”. Conclusions Our findings highlight the need for health professionals to identify adolescents with major disease-related problems. The food industry should improve its range of gluten-free food products and public bodies and institutions should promote informative campaigns and help promote the overall quality of life of children and adolescents with CD. PMID:24304679

  19. Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients

    PubMed Central

    Saadah, Omar I.; Shaik, Noor Ahmad; Banaganapalli, Babajan; Salama, Mohammed A.; Al-Harthi, Sameer E.; Wang, Jun; Shawoosh, Harbi A.; Alghamdi, Sharifa A.; Bin-Taleb, Yagoub Y.; Alhussaini, Bakr H.; Elango, Ramu; Al-Aama, Jumana Y.

    2015-01-01

    Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17–0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD. PMID:26843707

  20. Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

    PubMed

    Hoffmanová, I; Sánchez, D; Hábová, V; Anděl, M; Tučková, L; Tlaskalová-Hogenová, H

    2015-01-01

    Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

  1. Non-celiac wheat sensitivity: differential diagnosis, triggers and implications.

    PubMed

    Schuppan, Detlef; Pickert, Geethanjali; Ashfaq-Khan, Muhammad; Zevallos, Victor

    2015-06-01

    Non allergy-non-celiac wheat sensitivity (NCWS) has become a common and often overrated diagnosis. Skepticism mainly relates to patients with prominent intestinal symptoms in the absence of general or intestinal signs of inflammation. There is consensus that the major wheat sensitivities, celiac disease and wheat allergy, have to be ruled out which may be difficult for wheat allergy. The non-inflammatory intolerances to carbohydrates, mainly lactose and FODMAPs (fermentable oligi-, di-, monosaccharides and polyols), which cause bloating or diarrhoea, can usually be excluded clinically or by simple tests. Recent studies and experimental data strongly indicate that NCWS exists in a substantial proportion of the population, that it is an innate immune reaction to wheat and that patients often present with extraintestinal symptoms, such as worsening of an underlying inflammatory disease in clear association with wheat consumption. Wheat amylase-trypsin inhibitors (ATIs) have been identified as the most likely triggers of NCWS. They are highly protease resistant and activate the toll-like receptor 4 (TLR4) complex in monocytes, macrophages and dendritic cells of the intestinal mucosa. Non-gluten containing cereals or staples display no or little TLR4 stimulating activity. Wheat ATIs are a family of up to 17 similar proteins of molecular weights around 15 kD and represent 2-4% of the wheat protein. With oral ingestion they costimulate antigen presenting cells and promote T cell activation in celiac disease, but also in other immune-mediated diseases within and outside the GI tract.

  2. Cost-Effectiveness of Universal Serological Screening to Prevent Non-Traumatic Hip and Vertebral Fractures in Patients with Celiac Disease

    PubMed Central

    Park, KT; Tsai, Raymond; Wang, Louise; Khavari, Nasim; Bachrach, Laura; Bass, Dorsey

    2013-01-01

    Background & Aims Patients with asymptomatic or poorly managed celiac disease can experience bone loss, placing them at risk for hip and vertebral fractures. We analyzed the cost-effectiveness of universal serologic screening (USS) vs symptomatic at-risk screening (SAS) strategies for celiac disease, given the risk of non-traumatic hip and vertebral fractures if untreated or undiagnosed. Method We developed a lifetime Markov model of the screening strategies, each with male or female cohorts of 1000 patients, 12 years old when screening began. We screened serum samples for levels of immunoglobulin A (IgA), compared with tissue transglutaminase and total IgA, and findings were confirmed by mucosal biopsy. Transition probabilities and quality of life estimates were obtained from the literature. We used generalizable cost estimates and Medicare reimbursement rates, and ran deterministic and probabilistic sensitivity analyses. Result For men, the average life-time costs were $8532 and $8472 for USS and SAS strategies, respectively, corresponding to average quality adjusted life years (QALY) gains of 25.511 and 25.515. Similarly, for women, costs were $11,383 and $11,328 for USS and SAS strategies, corresponding to QALY gains of 25.74 and 25.75. Compared to the current standard of care (SAS), USS produced higher average lifetime costs and lower quality of life for each sex. Deterministic and probabilistic sensitivity analyses showed that the model was robust to realistic changes in all the variables, making USS cost ineffective, based on these outcomes. Conclusion USS and SAS are similar in lifetime costs and quality of life, although the current SAS strategy was overall more cost effective in preventing bone loss and fractures among patients with undiagnosed or subclinical disease. Based on best available supportive evidence, it is more cost effective to maintain the standard celiac screening practices, although future robust population-based evidence in other health

  3. Prudence is necessary in the application of the new ESPGHAN criteria for celiac disease omitting duodenal biopsy: a case report.

    PubMed

    Schirru, Enrico; Jores, Rita-Désirée; Congia, Mauro

    2014-06-01

    New guidelines for celiac disease (CD) diagnosis from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) propose the option to omit the duodenal biopsy in the diagnosis of CD. For this option, all four of the following criteria have to apply in children and adolescents: signs and symptoms suggestive of CD, anti-transglutaminase type 2 antibody (anti-TG2) levels more than 10 times the upper limit of normal, positive confirmation tests of anti-endomysium-IgA antibodies (EMA), and at-risk HLA-DQ2 or HLA-DQ8. Here, we report the case of a female patient, 2 years old, with chronic diarrhea that started after an acute viral gastroenteritis. The patient had anti-TG2 levels of more than 10 times the upper limit of normal, positivity for EMA, antigliadin IgA, and IgG (AGA-IgA, AGA-IgG, respectively), and the at-risk HLA-DRB1*0301, DQB1*0201/DRB1*10, DQB1*0501 genotype, thus fulfilling all criteria for the diagnosis of CD. Although the diarrhea disappeared after about 5 weeks, anti-TG2, EMA, and AGA-IgG remained positive. Therefore, a duodenal biopsy was performed and evidenced a normal mucosa (Marsh 0). After about 18 months, the antibody titer for AGA-IgG, anti-TG2, and EMA became negative. The patient was all the time on a normal, gluten-containing diet. This clinical case represents an exception to the new ESPGHAN guidelines for CD diagnosis. During 5 weeks, the new ESPGHAN criteria were all fulfilled, allowing to propose for this patient the diagnosis of CD without performing a duodenal biopsy. Therefore, a prudent approach is suggested when the pediatric gastroenterologist makes a diagnosis of CD without duodenal biopsy. PMID:24694761

  4. Increased Risk for Vitamin D Deficiency in Obese Children with Both Celiac Disease and Type 1 Diabetes

    PubMed Central

    Setty-Shah, Nithya; Nwosu, Benjamin Udoka

    2014-01-01

    Background. It is unknown whether the coexistence of type 1 diabetes (T1D) and celiac disease (CD) increases the risk for vitamin D deficiency. Aims. To determine the vitamin D status and the risk for vitamin D deficiency in prepubertal children with both T1D and CD compared to controls, TID, and CD. Subjects and Methods. Characteristics of 62 prepubertal children of age 2–13 y with either CD + T1D (n = 22, 9.9 ± 3.1 y), CD only (n = 18, 8.9 ± 3.3 y), or T1D only (n = 22, 10.1 ± 2.8 y) were compared to 49 controls of the age of 8.0 ± 2.6 years. Vitamin D deficiency was defined as 25(OH)D < 50 nmol/L, overweight as BMI of >85th but <95th percentile, and obesity as BMI > 95th percentile. Results. The 4 groups had no difference in 25(OH)D (ANOVA P = 0.123) before stratification into normal-weight versus overweight/obese subtypes. Following stratification, 25(OH)D differed significantly between the subgroups (F(3,98) = 10.109, ANOVA P < 0.001). Post-hoc analysis showed a significantly lower 25(OH)D in the overweight/obese CD + T1D compared to the overweight/obese controls (P = 0.039) and the overweight/obese CD (P = 0.003). Subjects with CD + T1D were 3 times more likely to be vitamin D deficient (OR = 3.1 [0.8–11.9], P = 0.098), compared to controls. Conclusions. The coexistence of T1D and CD in overweight/obese prepubertal children may be associated with lower vitamin D concentration. PMID:25548555

  5. Increased Risk of Systemic Lupus Erythematosus in 29,000 Patients with Biopsy-verified Celiac Disease

    PubMed Central

    LUDVIGSSON, JONAS F.; RUBIO-TAPIA, ALBERTO; CHOWDHARY, VAIDEHI; MURRAY, JOSEPH A.; SIMARD, JULIA F.

    2012-01-01

    Objective To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking. Methods We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden’s 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE. Results During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48–4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57–4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22–4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97–4.17). Conclusion Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low. PMID:22859356

  6. 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

  7. An impending rupture of a celiac artery aneurysm in a patient with Behçet's disease -- extra-anatomic aorto-common hepatic artery bypass: report of a case.

    PubMed

    Maeda, Hideaki; Umezawa, Hisaki; Goshima, Masakazu; Hattori, Tsutomu; Nakamura, Tetsuya; Negishi, Nana