... small intestine. People with celiac disease cannot eat gluten, a protein found in wheat, barley, and rye. ... Treatment Doctors treat celiac disease by prescribing a gluten-free diet. Symptoms significantly improve for most people ...
... 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 ...
Celiac disease is a genetically determined, permanent intolerance to gluten, a protein complex found in wheat, rye and barley. As many as 1:163 people are affected by it, but only a small percentage are aware of the condition, which begins either in infancy, with gastrointestinal symptoms, or in childhood and later years with non-Gl signs and symptoms, such as fatigue, depression, anxiety, anemia, stunted growth, and delayed puberty. A strong association with Type 1 diabetes and Down syndrome is also found, thus making screening mandatory for these subjects. Celiac disease is often entirely clinically silent, yet it must be detected in order to prevent long-term complications.
Green, Peter H R; Lebwohl, Benjamin; Greywoode, Ruby
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.
... of Pediatric Gastroenterology and Nutrition Nurses Print Share Celiac Disease Many kids have sensitivities to certain foods, ... protein found in wheat, rye, and barley. Pediatric Celiac Disease If your child has celiac disease, consuming ...
Scherer, John R
Celiac disease is an autoimmune disorder caused by the continued ingestion of gluten, a protein found in wheat, barley and rye, by predisposed individuals. With the development of highly sensitive serologic tests, this has become an increasingly recognized disease with prevalence as high as 1% in certain patient populations, such as Caucasian females. Almost all celiac patients carry the human leukocyte antigen DQ2/DQ8 gene. Much has recently been discovered about the role of the innate immune system in exposing genetically vulnerable patients to the pathogenic gliadin fraction of gluten. The "classical" presentation of chronic diarrhea and malabsorption is now a rarity. Due to earlier detection and increased awareness, celiac disease now presents with a myriad of "atypical" signs and symptoms such as iron-deficiency anemia and osteoporosis. Associated conditions include T-cell lymphoma, dermatitis herpetiformis, autoimmune thyroiditis and type 1 diabetes. Diagnosis requires serologic confirmation with either antiendomysial or antitransglutaminase antibodies as well as histologic confirmation from endoscopic small bowel biopsy. The only effective treatment necessitates a lifelong, continual adherence to a gluten-free diet.
Celiac disease (CD) is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-II antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 (tTG), appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the “gold standard” for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.
Celiac disease is an immunologically mediated enteropathy of the small intestine, characterized by lifelong intolerance to the gliadin and related prolamines from wheat and other cereals, that occurs in genetically predisposed individuals. Symptoms result from structural damage to the mucosa of the small intestine, which may cause malabsorption with positive autoantibodies in the sera. Normal mucosal architecture is restored after the use of a gluten-free diet and the normalization of the autoantibodies. Villous atrophy and high levels of autoantibodies reappear when gluten is reintroduced into the diet (gluten challenge).
... Disease How do doctors treat celiac disease? A gluten-free diet Doctors treat celiac disease with a ... absorb nutrients from food into the bloodstream normally. Gluten-free diet and dermatitis herpetiformis If you have ...
... gluten, a protein found in wheat, rye, and barley. Gluten is poison to people who have celiac ... free diet avoid all foods that contain wheat, barley, rye, spelt, and triticale products, including many breads, ...
... your provider if you have symptoms of celiac disease. Prevention Because the exact cause is unknown, there is no known way to prevent the development of celiac disease. However, being aware of the risk factors (such ...
Lecornu, M; David, L; François, R
In 4 children with celiac disease, aged 7 months to 11 years, serum somatomedin activities (SMA) were consistently low: less than 0.40 U/ml (N greater than 0.50 U/ml). Basal plasma growth hormone (GH) levels were not elevated and increased normally under arginine-insulin stimulation in 3 patients. Human GH administration at a dosage which usually determines an increase of serum SMA in children with GH deficiency (4 mg/day/2 days) did not modify significantly the low serum SMA. However, in 1 child a clear-cut increase of serum SMA (0.22-0.82 U/ml) was noted under a higher dosage of human GH (8 mg/day/2 days). In 3 patients serum SMA was studied 3 weeks to 4 months after starting the gluten-free diet and was found to be normal. A limitation of the somatomedin generation unrelated to a deficit in GH secretion and probably resistant to GH appears therefore to be present in celiac disease. The rapid normalization of serum SMA under gluten-free diet suggests that the low serum SMA is induced through some unknown hormonal or metabolic signal by the protein malabsorption and/or the nutritional deficiency present in celiac disease.
Hancock, Rebecca; Koren, Gideon
QUESTION: One of my patients was diagnosed with celiac disease and maintains a strict gluten-free diet. Is her fetus at risk of neural tube defects because she does not get folic acid from bread and other flour-based foods? ANSWER: A woman with celiac disease must supplement her diet with multivitamins, including folic acid. Most prenatal vitamins contain 0.8 to 0.9 mg of folic acid, double the amount recommended by Health Canada for prevention of neural tube defects. Without supplementation (eg, undiagnosed pregnancy), women with celiac disease might not take in enough folate to maintain protective levels. PMID:15526871
Lihabi, Abeer Ayad Al
Trichotillomania is an underreported and underdiagnosed condition associated with significant impairments in social and functional relationships. The connection between celiac disease and trichotillomania is not yet established clearly. Only a few cases of trichotillomania have been reported to date. Here, we report the case of a 22-year-old Saudi female, who presented with celiac disease and trichotillomania to the psychiatry clinic. This is the first report of its kind in Saudi Arabia. By reporting this case, I highlight the importance of psychiatric and comprehensive approaches in patients with celiac disease. PMID:27920650
Marasco, Giovanni; Di Biase, Anna Rita; Schiumerini, Ramona; Eusebi, Leonardo Henry; Iughetti, Lorenzo; Ravaioli, Federico; Scaioli, Eleonora; Colecchia, Antonio; Festi, Davide
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.
Garnier-Lengliné, Hélène; Cerf-Bensussan, Nadine; Ruemmele, Frank M
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.
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
Zanchetta, María Belén; Longobardi, Vanesa; Bai, Julio César
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.
Martins, Thiago Gonçalves dos Santos; Costa, Ana Luiza Fontes de Azevedo; Oyamada, Maria Kiyoko; Schor, Paulo; Sipahi, Aytan Miranda
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
Pelkowski, Timothy D; Viera, Anthony J
Celiac disease is an autoimmune disorder of the gastrointestinal tract. It is triggered by exposure to dietary gluten in genetically susceptible individuals. Gluten is a storage protein in wheat, rye, and barley, which are staples in many American diets. Celiac disease is characterized by chronic inflammation of the small intestinal mucosa, which leads to atrophy of the small intestinal villi and subsequent malabsorption. The condition may develop at any age. Intestinal manifestations include diarrhea and weight loss. Common extraintestinal manifestations include iron deficiency anemia, decreased bone mineral density, and neuropathy. Most cases of celiac disease are diagnosed in persons with extraintestinal manifestations. The presence of dermatitis herpetiformis is pathognomonic for celiac disease. Diagnosis is supported by a positive tissue transglutaminase serologic test but, in general, should be confirmed by a small bowel biopsy showing the characteristic histology associated with celiac disease. The presence of human leukocyte antigen alleles DQ2, DQ8, or both is essential for the development of celiac disease, and can be a useful genetic test in select instances. Treatment of celiac disease is a gluten-free diet. Dietary education should focus on identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. About 5% of patients with celiac disease are refractory to a gluten-free diet. These patients should be referred to a gastroenterologist for reconsideration of the diagnosis or for aggressive treatment of refractory celiac disease, which may involve corticosteroids and immunomodulators.
Perfetti, Vittorio; Baldanti, Fausto; Lenti, Marco Vincenzo; Vanoli, Alessandro; Biagi, Federico; Gatti, Marta; Riboni, Roberta; Dallera, Elena; Paulli, Marco; Pedrazzoli, Paolo; Corazza, Gino Roberto
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.
Camarca, Alessandra; Del Mastro, Andrea; Gianfrani, Carmen
Celiac disease is a common and lifelong food intolerance, affecting approximately 1% of the population. Because of a mechanism not completely understood, the ingestion of wheat gluten, and of homologue proteins of barley and rye, induces in genetically predisposed individuals pronounced inflammatory reactions mainly at the site of small intestine. Gluten, the triggering factor, is a complex protein mixture highly resistant to the gastrointestinal enzymatic proteolysis, and this results in the presence of large, and potentially immunogenic, peptides at the intestinal mucosa surface. During the last decade, several studies have defined gluten peptides able to stimulate adaptive T cells, of either CD4 or CD8 phenotype, and to activate innate (non T) immune cells. This review examines the complete repertoire of gluten peptides recognized by celiac T cells and discusses the several translational implications that the identification of these epitopes opens.
Kalra, K K; Jain, N; Mittal, S K
Celiac disease (CD), perceived as a rare cause of chronic diarrhea three decades ago, was diagnosed as a cause of diarrhea in 60 (7.5%) post weaned children among 800 cases of chronic diarrhea. The diagnosis was established on the basis of a detailed clinical history, histopathological studies on small bowel mucosa and a complete recovery on gluten free diets. Thirty four children were followed up for a period of 0.3 to 8.2 years (mean 3.45 +/- 2.28). Catch up growth was seen in all. A rapid gain in height and weight was observed in first year following exclusion of gluten from the diet. However, on subsequent follow up, flattening of growth curve was seen in 9 subjects which was attributed to non-compliance of gluten free diets and dietary inadequacies. Strict dietary compliance is difficult to adhere to with wheat being a staple cereal in India. Other factors affecting compliance include lack of awareness and non availability of gluten free diets as well as contamination of other items with wheat at grocery shops. A few cases may present as celiac crisis which is a medical emergency requiring aggressive management including use of corticosteroids to improve survival in this otherwise life threatening situation. Effective management of CD requires intense family cooperation as well as concerted national efforts to provide these patients easy access to gluten free diets. The evolution of Celiac Societies, and widespread dissemination of knowledge through all available media will greatly help in management of patients with this chronic disease.
McCarville, Justin L; Caminero, Alberto; Verdu, Elena F
Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten, characterized by immune responses toward gluten constituents and the autoantigen transglutaminase 2. The only current treatment available for celiac disease is a gluten-free diet, however there are a plethora of therapies in development for the treatment of celiac disease (e.g. vaccine), management of symptoms while consuming gluten (e.g. Necator americanus) or adjuvant therapies in conjunction with the gluten-free diet (e.g. larazotide acetate). Current approaches in development target barrier function, immune responses, detoxifying gluten or sequestering gluten. Developing therapies include those targeting environmental factors, such as the microbiota or proteases.
Diagnosis If antibody tests and symptoms suggest celiac disease, the physician needs to establish the diagnosis by obtaining tiny pieces of tissue from the upper small intestine to check for damage ...
... news/fullstory_164453.html Study Links Celiac Disease, Anorexia Chances of being diagnosed with eating disorder were ... face a heightened risk of being diagnosed with anorexia, a new study suggests. The Swedish researchers found ...
Urban-Kowalczyk, Małgorzata; Œmigielski, Janusz; Gmitrowicz, Agnieszka
Background Neuropsychiatric symptoms may represent an atypical manifestation of celiac disease that occur before a gastroenterological diagnosis is made. Some studies suggest that a gluten-free diet is effective in treating the depression, anxiety, and neurological complications associated with celiac disease. Method The article describes the case of a patient suffering from chronic, treatment-resistant symptoms of depression and anxiety. The diagnosis of celiac disease and introduction of an elimination diet caused a significant improvement in mental state and everyday functioning in the presenting patient. Conclusion The presence of persistent anxiety and depressive symptoms, with a poor reaction to pharmacological treatment, indicates a need to identify somatic reasons for the underlying condition. It is important to remember that celiac disease can occur at any age, not only in childhood. The presence of this somatic cause of persistent depressive and anxiety symptoms should be considered in the diagnostic process in adults. PMID:25342904
... Urodynamic Testing Virtual Colonoscopy Celiac Disease Testing (for Health Care Professionals) Serologic tests for celiac disease provide an ... 6332) or visit www.fda.gov . Consult your health care provider for more information. September 2013 Share Alternate ...
Gobbetti, Marco; Giuseppe Rizzello, Carlo; Di Cagno, Raffaella; De Angelis, Maria
Celiac disease (CD) is one of the most common food intolerance. The only effective treatment for CD is a strict adherence to a gluten-free diet throughout the patient's lifetime. Gluten-free products are not widely available and are usually more expensive than their gluten-containing counterparts. There is, therefore, an urgent need to develop safe and effective therapeutic alternatives, to develop high-quality gluten-free products and to investigate the potential of the bread making biotechnology following ancient protocols which include long-time fermentation by selected sourdough lactic acid bacteria. This review describes the most relevant results related to biotechnologies that use selected sourdough lactic acid bacteria and probiotics as starters for sourdough fermentation to investigate their potential to decrease the risk of gluten contamination in gluten-free products. As shown by studies in vitro on celiac intestinal tissue and in vivo on CD patients, the bacterial proteolytic activity is rather promising not only as currently demonstrated for eliminating traces of contaminant gluten but probably also in perspective for the manufacture of tolerated baked goods.
... Tract Imaging Urodynamic Testing Virtual Colonoscopy Celiac Disease Testing (for Health Care Professionals) Serologic tests for celiac ... MA, Loots CM, Salvatore S, Vandenplas Y, ESPGHAN EURO-PIG Working Group. Indications, methodology, and interpretation of combined ...
Pedrosa Delgado, M; Martín Muñoz, F; Polanco Allué, I; Martín Esteban, M
Cold urticaria can be associated with blood and thyroid disorders, drugs, or infections. Celiac disease is an autoimmune enteropathy caused by permanent gluten intolerance. It is often associated with other autoimmune diseases, such as chronic idiopathic urticaria. Nevertheless, association with cold urticaria has not yet been described. A boy aged 3 years 8 months presented local urticaria-angioedema when exposed to cold temperatures. An ice cube test was positive and iron deficiency anemia was demonstrated. He later developed legume intolerance, rhinoconjunctivitis related to pollen sensitization, and asthma. Due to persistence of cold urticaria symptoms and refractory anemia, a test for immunoglobulin A autoantibodies to tissue transglutaminase and an intestinal biopsy were performed. Results of both tests were compatible with celiac disease.A study of human leukocyte antigen indicated a high risk phenotype (HLA, DR6/DR7; DQA 0501, 0201; DQB 0301, 0201). After 7 months of a gluten-free diet, the boy's anemia resolved and he is free of symptoms when exposed to cold. This is a first description of the possibility of an association between celiac disease and cold urticaria. A poor course of cold urticaria in the absence of evidence of another underlying condition should lead to suspicion of celiac disease.
Lebwohl, Benjamin; Ludvigsson, Jonas F; Green, Peter H R
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.
Lebwohl, Benjamin; Ludvigsson, Jonas F
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
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.
Shannahan, Sarah; Leffler, Daniel A
Celiac disease is an autoimmune disorder induced by gluten in genetically susceptible individuals. It can result in intraintestinal and extraintestinal manifestations of disease including diarrhea, weight loss, anemia, osteoporosis, or lymphoma. Diagnosis of celiac disease is made through initial serologic testing and then confirmed by histopathologic examination of duodenal biopsies. Generally celiac disease is a benign disorder with a good prognosis in those who adhere to a gluten-free diet. However, in refractory disease, complications may develop that warrant additional testing with more advanced radiologic and endoscopic methods. This article reviews the current strategy to diagnose celiac disease and the newer modalities to assess for associated complications.
Girbovan, Anamaria; Sur, Genel; Samasca, Gabriel; Lupan, Iulia
Celiac disease remains one of the most challenging pathologies of the small intestine. It involves multiple pathogenic pathways and there are no disease-changing pharmacological agents available against it yet. The term microbiota refers to the community of microorganisms that inhabit a particular region of the body. Normal gut microbiota has a vital role in maintaining the intestinal homeostasis and promoting health. Celiac disease is associated with microbiota alteration, especially with an increase in the number of Gram-negative bacteria and a decrease in the number of Gram-positive bacteria. There is a strong relationship between intestinal dysbiosis and celiac disease, and recent studies are aimed at determining whether the celiac disease is a risk factor for dysbiosis or dysbiosis is for celiac disease. Therefore, the aim of this review was to assess the latest findings regarding the gut microbiota and its impact on the celiac disease, including therapeutic aspects.
Selimoğlu, Mukadder Ayşe; Karabiber, Hamza
Celiac disease is a common multisystemic disorder that may be diagnosed at any age. Owing to the increasing prevalence, prevention strategies, including encouragement of breastfeeding and introduction of small amounts of gluten whereas still on breastfeeding at fourth to sixth month of age, become more important than before. For avoiding complications of celiac disease, a strict gluten-free diet is essential. A lifelong gluten-free diet may bring about difficulties as avoiding gluten completely is problematic owing to the contamination with gluten of presumably gluten free foods. New therapeutic approaches include enzyme supplementation, correction of the intestinal barrier defect against gluten entry, blocking of gliadin presentation by human leukocyte antigen blockers and tissue transglutaminase inhibitors.
Tronconi, G M; Parma, B; Barera, G
It is known that celiac disease is characterized by a huge variety of clinical forms ranging from classical ones to silent forms, potential ones and to an increased number of cases of gluten-sensitivity. The latter is an abnormal non-allergic sensibility to gluten. Clinical manifestations can be very different without a severe intestinal damage (Marsh/Oberhuber 0-I) and this condition seems to benefit from a gluten free diet. Cases of gluten-sensitivity appear very interesting in the search of histological markers with elevated specificity, which are able to identify slight and early gluten dependent enteropathy, especially in at risk patients for celiac disease even before classical autoantibodies appear: for instance, this is the case of intraepithelial lymphocytes T-cell receptor gamma delta and mucosal deposits of class IgA anti transglutaminase antibodies. Other studies are investigating transglutaminase isoenzimes (different from tissue one), that can be identified in patients with gluten dependent symptoms without classical autoantibodies. Forms of gluten allergy have a different pathogenesis from celiac disease and are represented by "backer's asthma" or by classical allergy to wheat proteins. Clinical manifestations can vary from anaphylactic reactions to dermatological, respiratory and intestinal symptoms. Also in these cases the therapeutic approach is based on gluten free diet.
Abenavoli, L; Proietti, I; Leggio, L; Ferrulli, A; Vonghia, L; Capizzi, R; Rotoli, M; Amerio, PL; Gasbarrini, G; Addolorato, G
Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed. PMID:16521210
Simila, Seppo; Kokkonen, Jourma
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)
Recent diagnostic advances have demonstrated that celiac disease is relatively common although most patients have less florid symptoms than previously recognised. The mucosal lesion of this autoimmune disorder depends on both adaptive and innate immune responses. The characteristic antibodies to tissue transglutaminase-2 (tTG-2) and deamidated gliadin peptides may be produced in persons possessing the relevant HLA-DQ genotypes if intact gliadin peptides can penetrate the epithelial barrier to reach antigen presenting cells. Progression from celiac autoimmunity to overt disease may depend on innate immune mechanisms, not HLA-restricted, where IL-15 is generated within the epithelial compartment. A specific innate immune response previously thought restricted to invertebrates, the encapsulation reaction, may contribute to mucosal volume expansion through recruitment of syndecan-expressing leukocytes and stimulated matrix production. It is notable that tissue transglutaminase is critical in this reaction in insects, and that the very few insects that can predate wheat, possess specific salivary or intestinal enzymes that degrade gluten. Animal models in HLA-DQ transgenic mice suggest that the microbial flora of the intestine may play a role in host responses and modulate the evolution of the disease. This suggests that therapeutic modulation of the microbiome may contribute to management of celiac disease. In developing world countries, there is a potential difficulty in histological diagnosis because of the widespread incidence of environmental enteropathy amongst apparently healthy children. Thus, recognition of local patterns of enteropathy will be important for histopathologists, and high titre tTG-2 autoantibody titres may hold considerable diagnostic significance.
Simpson, Suzanne; Thompson, Tricia
The gluten-free diet is currently the only treatment for celiac disease, and patients should be monitored closely by a dietitian who is knowledgeable regarding this diet. Evaluation by a dietitian includes a comprehensive assessment of dietary history, with an emphasis on caloric and micronutrient intake. Patient knowledge of the gluten-free diet is assessed and interpretation of food labels is taught. Identification of micronutrient deficiencies or comorbid gastrointestinal conditions may occur during a comprehensive dietary assessment. In patients with evidence of gluten exposure, a thorough evaluation for cross-contamination is performed.
Casella, Giovanni; Orfanotti, Guido; Giacomantonio, Loredana; Bella, Camillo Di; Crisafulli, Valentina; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio
Celiac disease (CD) shows an increased prevalence in female, particularly during the fertile period. Celiac disease should be researched in infertility, spontaneous and recurrent abortions, delayed menarche, amenorrhea, early menopause, and children with low birth-weight. Celiac disease is still little considered during the evaluation of infertility. Up to 50% of women with untreated CD refer an experience of miscarriage or an unfavorable outcome of pregnancy. Celiac patients taking a normal diet (with gluten) have a shorter reproductive period. Women with undiagnosed CD had a higher risk of small for gestation age infants very small for gestational age infants and pre-term birth when compared with women with noted CD. The link between NCGS and infertility is actually unknown. The goal of our work is to perform an actual review about this topic and to increase the awareness in the medical population to research celiac disease in selected obstetric and gynecological disorders. PMID:27895849
Plugis, Nicholas M.; Khosla, Chaitan
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
... disease, dental enamel defects, and more. Gluten-free starches The following grains and starches are allowed on a gluten-free diet: Amaranth ... Rye Semolina Spelt Triticale Wheat Wheat Germ Wheat Starch Gluten Intolerance Group (GIG) 31214 – 124th Ave. S.E. ...
Devlin, Shane M.; Andrews, Christopher N.; Beck, Paul L.
OBJECTIVE: To review current understanding of the epidemiology, pathophysiology, diagnosis, and management of celiac disease. QUALITY OF EVIDENCE: Few recent randomized controlled trials (level I evidence) have studied treatments for celiac disease. There are recent comparative studies (level II evidence) and there is well established consensus (level III evidence) on diagnosis and treatment of celiac disease. MAIN MESSAGE: Celiac disease is an immune-mediated small bowel enteropathy caused by exposure to wheat gluten protein. The disease can be insidious and often presents with only subtle extraintestinal manifestations in a variety of organ systems. Recent epidemiologic surveys suggest celiac disease is much more common in North America than previously thought. Advances in immunology and screening have made diagnosis more reliable than in the past. Removing gluten from the diet is effective in most cases. CONCLUSION: Celiac disease manifests subtly and is an easy diagnosis to miss. Good laboratory screening tests and effective treatment are available. Family practitioners should consider celiac disease in patients who present with confounding symptoms. PMID:15171674
Tchidjou, Hyppolite K.; De Matteis, Arianna; Di Iorio, Laura; Finocchi, Andrea
Celiac disease (CD) is an inflammatory disease of the small intestine. A complete management and differential diagnosis of such disease includes food intolerances, intestinal infections, and irritable bowel syndrome. We describe an 8-years-old adoptive girl from Congo with negative medical history. Patient followed for recurrent abdominal pain and diarrhea associated to Giardia infection, unresponsive to antiparasitic therapy. Persistence of symptoms despite antiparasitic therapy, prompted us to perform: 1- Blood screening of Celiac disease, which was negative; 2- Genetic evaluation of celiac disease, which revealed the presence of HLA-DQ2 heterodimer; and 3- Esophagogastroduodenoscopy, which showed duodenal villous atrophy and crypt hyperplasia, associated with Helicobacter Pylori infection. The child was treated in accordance with international recommendations using a Gluten-free diet and specific antibiotics, which lead to the resolution of the symptoms. Our patient’s clinical history seems peculiar, considering that, recurrent Giardiasis may mimic the symptoms of Celiac disease and may simulate clinical and histological picture of active Celiac disease. Early diagnosis may help prevent the complications of untreated celiac disease. PMID:26309440
Tchidjou, Hyppolite K; De Matteis, Arianna; Di Iorio, Laura; Finocchi, Andrea
Celiac disease (CD) is an inflammatory disease of the small intestine. A complete management and differential diagnosis of such disease includes food intolerances, intestinal infections, and irritable bowel syndrome. We describe an 8-years-old adoptive girl from Congo with negative medical history. Patient followed for recurrent abdominal pain and diarrhea associated to Giardia infection, unresponsive to antiparasitic therapy. Persistence of symptoms despite antiparasitic therapy, prompted us to perform: 1- Blood screening of Celiac disease, which was negative; 2- Genetic evaluation of celiac disease, which revealed the presence of HLA-DQ2 heterodimer; and 3- Esophagogastroduodenoscopy, which showed duodenal villous atrophy and crypt hyperplasia, associated with Helicobacter Pylori infection. The child was treated in accordance with international recommendations using a Gluten-free diet and specific antibiotics, which lead to the resolution of the symptoms. Our patient's clinical history seems peculiar, considering that, recurrent Giardiasis may mimic the symptoms of Celiac disease and may simulate clinical and histological picture of active Celiac disease. Early diagnosis may help prevent the complications of untreated celiac disease.
Murray, J A
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.
Celiac disease develops from an autoimmune response to specific dietary grains that contain gluten. Diagnosis can be made based on the classical presentation of diarrhea, fatty stools, and abdominal bloating and cramping, as well as the presence of specific serum antibodies. In addition, gluten ingestion has increasingly been found to be associated with other conditions not usually correlated with gluten intolerance. The subsequent diversity of the clinical presentation in these cases can complicate decision-making and delay treatment initiation in conditions such as ataxia, headaches, arthritis, neuropathy, type 1 diabetes mellitus, and others. This review explores the etiology and pathology of celiac disease, presents support for the relationship between gluten and other diseases, and provides effective screening and treatment protocols.
Torres, MI; López Casado, MA; Ríos, A
Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA-DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. CD is caused by the lack of immune tolerance (oral tolerance) to wheat gluten. In this sense, the expression of soluble HLA-G in CD is of special interest because the molecule plays an important role in the induction of immune tolerance. The enhanced expression of soluble HLA-G found in CD may be part of a mechanism to restore the gluten intolerance. In this editorial, we review recent progress in understanding CD in relation to its prevalence, diagnosis and possible mechanisms of pathogenesis. PMID:17451193
Jones, B.; Bayless, T.M.; Fishman, E.K.; Siegelman, S.S.
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.
... is director of research at the University of Chicago's Celiac Disease Center. "However, the specific virus and ... 7 in the journal Science . SOURCE: University of Chicago, news release, April 6, 2017 HealthDay Copyright (c) ...
Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César
Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had
Freeman, Hugh James
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.
Freeman, Hugh James
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
Freeman, Hugh James
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
Dore, Maria Pina; Pes, Giovanni Mario; Rocchi, Chiara; Loria, Maria Francesca; Soro, Sara; Bassotti, Gabrio
Abstract Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated. Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous. 3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not. Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study. PMID:28151870
Stazi, Anna Velia; Trinti, Biagino
In the past, celiac disease (CD), or intolerance to gluten, was considered a rare disease of infancy characterized by chronic diarrhea with malabsorption and delayed growth. Besides the overt enteropathy, there are other clinic and subclinical forms which appear later in life. Target organs are not limited to the gut, but include liver, thyroid, skin and female and male reproductive systems. CD interference on reproduction is related to the multifactorial nature of the disease, whose pathological manifestations can be modulated, besides gluten, by different concurrent genetic and environmental factors. CD induces malabsorption with consequent deficiencies of micronutrients such as iron, folic acid and vitamin K, which are essential for organogenesis, and fat-soluble vitamins important for spermatogenesis. Regarding endocrine disorders, the deficiencies of specific trace elements on ovarian function could explain its involvement in the increased risk of female osteoporosis in CD patients. Affected males show a picture of tissue resistance to androgens; the increases of follicle-stimulating hormone and prolactin, not associated with infertility, may indicate an imbalance at hypothalamus-pituitary level, with general effects on health. Since reproductive alterations are reversible, adoption of a gluten-free diet supported by early diagnosis is important. Therefore, the detection of early biomarkers, such as deficiencies of vitamins and/or iron and andrological or endocrinological dysfunctions, should trigger timely strategies for prevention and treatment.
Qiao, Shuo-Wang; Iversen, Rasmus; Ráki, Melinda; Sollid, Ludvig M
Compared to other human leukocyte antigen (HLA)-associated diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, fundamental aspects of the pathogenesis in celiac disease are relatively well understood. This is mostly because the causative antigen in celiac disease-cereal gluten proteins-is known and the culprit HLA molecules are well defined. This has facilitated the dissection of the disease-relevant CD4+ T cells interacting with the disease-associated HLA molecules. In addition, celiac disease has distinct antibody responses to gluten and the autoantigen transglutaminase 2, which give strong handles to understand all sides of the adaptive immune response leading to disease. Here we review recent developments in the understanding of the role of T cells, B cells, and antigen-presenting cells in the pathogenic immune response of this instructive disorder.
... Field, with 40,000 seats) to watch the Chicago White Sox 55 times. • U.S. fans with celiac ... could fill Soldier Field, the home of the Chicago Bears, 37 times. • The number of people with ...
That celiac disease is a lifelong disorder was suggested by clinical case records and was considered to have been demonstrated through the widespread use of intestinal biopsies by the end of the 1950s. It was clear that the mucosal lesions observed in children and adults were identical and responded similarly to gluten withdrawal. In fact, in 1970 the European Society for Paediatric Gastroenterology and Nutrition instituted the practice of a challenge after diagnosis. A relapse of clinical symptoms and of the intestinal lesions after gluten was reintroduced into the diet demonstrated the "permanent" nature of sensitivity to gluten in children with celiac disease. Twenty-five years later, the permanence of the sensitivity of the intestinal mucosa to gluten is again a matter of debate. Several lines of evidence, gathered during recent years, show that celiac disease is not always a lifelong condition. First, the long-term follow-up of children with proven celiac disease shows that 10% to 20% of them become "tolerant" (defined on clinical, biological and histologic grounds) to gluten during adolescence. Second, it has also been shown, in individual cases, that the mucosal lesions typical of the disease may appear during adulthood. Our increasing knowledge of the long-term evolution of the disease suggests that celiac disease develops and, in some cases, fades in a predisposed group of people with intestinal sensitivity to gluten, which is probably a common condition. The factors leading to the appearance or disappearance of the disease, however, are still unknown.
Medical nutrition therapy is the only accepted treatment for celiac disease. This paper summarizes a review of scientific studies using the gluten-free diet, nutritional risk factors, controversial elements of the diet, and its implementation in treating celiac disease. Treatment for celiac disease requires elimination of the storage proteins found in wheat, rye, and barley. The inclusion of oats and wheat starch is controversial. Research supports that oats may be acceptable for patients with celiac disease and can improve the nutritional quality of the diet. However, use of oats is not widely recommended in the United States because of concerns of potential contamination of commercial oats. Studies assessing the contamination of commercial oats are limited. Research indicates no differences in patients choosing a strict wheat starch-containing, gluten-free diet vs. a naturally gluten-free diet. Factors other than trace gluten may be the cause of continued villous atrophy in some patients. The impact of nutrient malabsorption caused from untreated celiac disease is well documented. The diet and gluten-free products are often low in B vitamins, calcium, vitamin D, iron, zinc, magnesium, and fiber. Few gluten-free products are enriched or fortified, adding to the risk of nutrient deficiencies. Patients newly diagnosed or inadequately treated have low bone mineral density, imbalanced macronutrients, low fiber intake, and micronutrient deficiencies. Also troubling is the increased incidence of obesity seen in persons with celiac disease following a gluten-free diet. Because of the nutritional risks associated with celiac disease, a registered dietitian must be part of the health care team that monitors the patient's nutritional status and compliance on a regular basis.
Passananti, V.; Siniscalchi, M.; Zingone, F.; Bucci, C.; Tortora, R.; Iovino, P.; Ciacci, C.
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
... Quinoa Well Tolerated in Patients with Celiac Disease Quinoa Well Tolerated in Patients with Celiac Disease FOR ... 263-9000 Bethesda, Maryland (January 21, 2014) – Adding quinoa to the gluten-free diet of patients with ...
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
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
Rashid, Mohsin; Lee, Jennie
Abstract Objective To address the questions and challenges commonly faced by primary care physicians when ordering serologic tests for celiac disease (CD) and provide practical clinical tips to help in the interpretation of test results. Sources of information MEDLINE was searched from 2000 to 2015 for English-language guidelines on the diagnosis and management of CD published by professional gastroenterological organizations. Main message To screen patients for CD, measurement of the immunoglobulin A (IgA) tissue transglutaminase antibody is the preferred test. Total serum IgA level should be measured to exclude selective IgA deficiency and to avoid false-negative test results. Patients with positive serologic test results should be referred to a gastroenterologist for endoscopic small intestinal biopsies to confirm the diagnosis. Testing for human leukocyte antigens DQ2 and DQ8 can help exclude the diagnosis. A gluten-free diet should not be started before confirming the diagnosis of CD. Conclusion Serologic testing is very useful for screening patients with suspected CD. Early diagnosis is essential to prevent complications of CD. PMID:26796833
Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H
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.
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…
León, Alberto J; Garrote, José A; Arranz, Eduardo
Celiac disease is manifested by an enteropathy caused by intolerance to gluten, a family of proteins found in wheat and other cereals. Following intestinal T-cell activation in predisposed individuals, different inflammatory mechanisms are triggered under the control of the cytokine balance including those with a pro-inflammatory Th1 pattern such as IFNgamma, TNFalpha, IL-15 and IL-18; and regulatory cytokines such as TGFbeta and IL-10. These cytokines, besides increasing the intensity of the activation and the number of immune cells within the intestinal mucosa, regulate the activity of epithelial growth factors and metalloproteinases, a group of molecules involved in the maintenance and turnover of the intestinal mucosa structure; in inflammatory conditions, they also induce the intestinal lesion responsible for malabsorption syndrome.
Tjon, Jennifer May-Ling; van Bergen, Jeroen; Koning, Frits
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.
Cappello, Maria; Morreale, Gaetano C.; Licata, Anna
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
LeBoff, Meryl S.; Cobb, Haley; Gao, Lisa Y.; Hawkes, William; Yu-Yahiro, Janet; Kolatkar, Nikheel S.; Magaziner, Jay
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
Due to the increased immune activation in the intestinal tract of people with celiac disease, the digestive and absorptive processes of those affected may be compromised. Individuals with celiac disease are more susceptible to pancreatic insufficiencies, dysbiosis, lactase insufficiencies, and folic acid, vitamin B12, iron, and vitamin D deficiencies, as well as accelerated bone loss due to an increase in inflammatory signaling molecules. Beyond strict maintenance of a gluten-free diet, research has shown benefit with additional nutritional supplementation to assist in regulation of several of these complications.
Adriaanse, Marlou; Leffler, Daniel A
The advent of highly reliable noninvasive celiac diagnostic tests has transformed the field of celiac disease, from diagnosis, to evaluation of epidemiology, to clinical and translational research. Serologic tests in their modern forms are highly sensitive and specific for diagnosis, allowing for consideration of avoidance of diagnostic intestinal biopsy in some settings. On the other hand, as predictors of intestinal damage and for use in monitoring disease activity, currently available noninvasive tests have been disappointing. Serologic tests, while a measure of disease activity, do not correlate well with histology or symptomatology, and it is unclear if they predict long-term risk. Additionally, while the many clinically available tests have improved accessibility, they can have widely different cutoff levels and overall performance, making the comparison of levels in individual patients over time and across populations quite difficult. In the future, we can expect to see improvement in the currently available serologic tests including tissue transglutaminase and deamidated gliadin peptide with expansion of the dynamic range of the tests, and the celiac care community should push for a standardization of assays that would simplify research and patient care. Additionally, current serologic tests are measures of the adaptive immune response in celiac disease but do not directly measure intestinal inflammation. Promising work on intestinal fatty acid-binding protein and other assays which directly measure intestinal damage may complement traditional serologic tests and further improve our ability to noninvasively diagnose and monitor celiac disease. The coming years hold promise for the continuing evolution of serum-based tests in celiac disease with the possibility of substantial improvement of patient care and clinical research.
Cârdei, E; Moraru, D; Trandafir, Laura; Bozomitu, Laura; Mihăilă, Doina
Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune enteropathy caused by the ingestion of gluten-containing grains in susceptible subjects. The authors present a 3 years and 5 months old girl diagnosed with celiac disease at 1 year and 5 months old. Initially, the evolution after gluten-free diet was favorable. After 2 years the child presented abdominal pain and anorexia. The IgA antigliadin antibodies had normal values. The gastric biopsy found Helicobacter pylori gastritis. After treatment for Helicobacter pylori eradication the symptoms disappeared.
Comino, Isabel; Moreno, María de Lourdes; Sousa, Carolina
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.
Comino, Isabel; Moreno, María de Lourdes; Sousa, Carolina
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
Horvath, K; Mehta, D I
Celiac disease and dermatitis herpetiformis are caused by the alcohol soluble fractions of wheat, barley, and rye. Reliable serological tests are available for both mass and risk group screening and recent epidemiological studies on celiac disease suggest that the prevalence varies between 1:100-300 in different continents. The clinical manifestations of the disease has changed in the West and the classical symptomatic cases represent only approximately 1/7th of all diagnosed cases. Symptoms such as, anemia, short stature, dental enamel defect or osteoporosis can be the only manifestations of the atypical disease. There is an increased prevalence of celiac disease in patients with autoimmune diseases. Recent data suggest that there is a correlation between the prevalence of autoimmune diseases and the number of years that an individual consumes gluten-containing foods. Genetic studies revealed a high prevalence of certain HLA antigens in celiac patients, however, there is likelihood that non-HIA genes are also important in the pathomechanism. An interesting new development is the recognition of tissue transglutaminase (tTG), an enzyme that probably forms an autoantigen with gluten. It is generally accepted that antibodies to tTG are identical to the previously described antiendomysium antibodies. Whether or not tTG is responsible for the initiation of an immunoreaction against prolamines or just exacerbates the immune response is a subject of further investigations.
Diamanti, Antonella; Capriati, Teresa; Basso, Maria Sole; Panetta, Fabio; Di Ciommo Laurora, Vincenzo Maria; Bellucci, Francesca; Cristofori, Fernanda; Francavilla, Ruggiero
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.
Harpreet, Singh; Deepak, Jain; Kiran, B
Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.
Harpreet, Singh; Kiran, B.
Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren’s syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients. PMID:28115785
Kagnoff, Martin F.
Celiac disease is characterized by small-intestinal mucosal injury and nutrient malabsorption in genetically susceptible individuals in response to the dietary ingestion of wheat gluten and similar proteins in barley and rye. Disease pathogenesis involves interactions among environmental, genetic, and immunological factors. Although celiac disease is predicted by screening studies to affect approximately 1% of the population of the United States and is seen both in children and in adults, 10%–15% or fewer of these individuals have been diagnosed and treated. This article focuses on the role of adaptive and innate immune mechanisms in the pathogenesis of celiac disease and how current concepts of immunopathogenesis might provide alternative approaches for treating celiac disease. PMID:17200705
Bul, Vadim; Sleesman, Brett; Boulay, Brian
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
Ströhle, Alexander; Wolters, Maike; Hahn, Andreas
Celiac disease is an autoimmune disorder resulting from gluten intolerance and is based on a genetically predisposition. Symptoms occur upon exposure to prolamin from wheat, rye, barley and related grain. The pathogenesis of celiac disease has not yet been sufficiently elucidated but is being considered as an autoimmune process. At its core are the deamidation of prolamin fragments, the building of specific antibodies and the activation of cytotoxic T-cells. The immunological inflammatory process is accompanied by structural damages of the enterocytes (villous atrophy, colonization and crypt hyperplasia). The symptoms and their extent depend on the type of the celiac disease; classic and non-classic forms are being distinguished (atypical, oligosymptomatic, latent and silent celiac disease). Characteristics of the classic presentation are malabsorption syndrome and intestinal symptoms such as mushy diarrhea and abdominal distension. The diagnosis of celiac disease is based on four pillars: Anamnesis and clinical presentation, serological evidence of coeliac specific antibodies (IgA-t-TG; IgA-EmA), small intestine biopsy and improvement of symptoms after institution of a gluten-free diet. The basis of the therapy is a lifelong gluten-free diet, i. e. wheat, rye, barley, spelt, green-core, faro-wheat, kamuth and conventional oats as well as food items obtained therefrom. Small amounts of up to 50 mg gluten per day are usually tolerated by most patients; amounts of > or = 100 mg/day lead mostly to symptoms. Gluten-free foods contain < or = 20 ppm or 20 mg/kg (Sign: symbol of the 'crossed ear' or label 'gluten-free'). At the beginning of the therapy the fat and lactose intake may need to be reduced; also the supplementation of single micronutrients (fat-soluble vitamins, folic acid, B12, iron, and calcium) may be required. Alternative therapies are being developed but have not yet been clinically tested.
In most patients the clinical course of celiac disease is unproblematic after the diagnosis has been made and a strict gluten-free diet is established. However, in rare cases complications like refractory sprue or lymphoma can occur. Individual management is required since the clinical presentation of celiac disease can be very heterogeneous. For example, it is a matter of controversy if asymptomatic patients, who have the same typical histological changes in their small bowel like patients with symptomatic celiac disease, should adhere to a gluten-free diet. A major problem is the compliance and the unintentional intake of gluten. A 100 % gluten-free diet is not possible since most food components are contaminated with trace amounts of gluten. Fortunately most patients tolerate these contaminations. Furthermore, the threshold for gluten contamination can differ highly among patients. One central point in patient care is the monitoring of a gluten-free diet and the timely recognition of complications. Therefore, the role of antibodies and duodenal histology in monitoring the course of the disease will be discussed.
Campbell, J. A.
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
Mulder, C J; Wierdsma, N J; Berkenpas, M; Jacobs, M A J M; Bouma, G
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.
Bul, Vadim; Sleesman, Brett; Boulay, Brian
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).
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…
Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa
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.
Picarelli, Antonio; Libanori, Valerio; De Nitto, Daniela; Saponara, Annarita; Di Tola, Marco; Donato, Giuseppe
Anti-endomysial and anti-transglutaminase antibodies can be produced in vitro by the intestinal mucosa of celiac disease (CD) patients in clinical remission, when the culture is performed in the presence of gliadin peptides. Our aim was to use this organ culture system as a means to detect the pathognomonic antibodies of celiac disease (CD) in the culture supernatants. Organ culture was performed in the presence of three different activators to evaluate which one induced the strongest antibody response in intestinal mucosa from patients in clinical remission of CD. Our data confirm the high efficiency of synthetic peptide 31-43 as a specific immunological activator in CD and demonstrate its capability to stimulate production/secretion of CD-specific antibodies. We envision that this organ culture system may prove to be useful as a new technique for CD diagnosis.
Isasi, Carlos; Tejerina, Eva; Morán, Luz M
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.
Niewinski, Mary M
Celiac disease is becoming an increasingly recognized autoimmune enteropathy caused by a permanent intolerance to gluten. Once thought to be a rare disease of childhood characterized by diarrhea, celiac disease is actually a multisystemic disorder that occurs as a result of an immune response to ingested gluten in genetically predisposed individuals. Screening studies have revealed that celiac disease is most common in asymptomatic adults in the United States. Although considerable scientific progress has been made in understanding celiac disease and in preventing or curing its manifestations, a strict gluten-free diet is the only treatment for celiac disease to date. Early diagnosis and treatment, together with regular follow-up visits with a dietitian, are necessary to ensure nutritional adequacy and to prevent malnutrition while adhering to the gluten-free diet for life. The purpose of this review is to provide clinicians with current updated information about celiac disease, its diverse clinical presentation and increased prevalence, the complex pathophysiology and strong genetic predisposition to celiac disease, and its diagnosis. This review focuses in detail on the gluten-free diet and the importance of intense expert dietary counseling for all patients with celiac disease. Recent advances in the gluten-free diet include food allergen labeling as well as the US Food and Drug Administration's proposed definition of the food-labeling term gluten-free. The gluten-free diet is complex and patients need comprehensive nutrition education from a skilled dietitian.
Zwolińska-Wcisło, Małgorzata; Galicka-Latała, Danuta; Rozpondek, Piotr; Rudnicka-Sosin, Lucyna; Mach, Tomasz
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.
Jandaghi, Elahe; Hojatnia, Mona; Vahedi, Homayoon; Shahbaz-Khani, Bijan; Kolahdoozan, Shadi; Ansari, Reza
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
Datta Gupta, S
Celiac disease is a gluten or prolamine-induced immunological disorder primarily affecting the intestines. Celiac disease is often missed since not only are clinical findings 'not typical' but also because many cases are asymptomatic. The diagnosis is based on a constellation of clinical, serological and histological findings in a duodenal biopsy, in addition to HLA genotype.and response to a gluten-free diet.Although some guidelines suggest that histology may not mandatory in every case, by and large changes in mucosal biopsies of the duodenum still remain an important diagnostic tool. The evaluation of a duodenal biopsy requires a properly oriented and satisfactory hematoxylin & eosin stained paraffin section. A poorly oriented and technically suboptimal biopsy is not uncommonly the reason for erroneous interpretation. An increase in intraepithelial lymphocytes [IELs] and an alteration of the crypt: villus ratio forms the basis of diagnosis. These are semiquantitavely classified. Despite varying opinions related to the cut-off values of IELs and findings that recommend appropriate site, number and size of the biopsy specimens, the sensitivity of biopsies vary from 90%-100%. Interpretation of histological findings require correlation with other evidences since the changes in duodenal biopsy may be similar to those seen in a host of other diseases including tropical sprue. It must also be mentioned that in the Indian subcontinent is that reference values for normal duodenal biopsies are lacking, making interpretation difficult especially when changes are mild. Histological changes in the duodenal mucosa often take months to normalize after clinical remission. This is a review of various aspects related to the histological changes in duodenal mucosal biopsies that aid in the diagnosis and follow-up of cases of celiac disease.
Rubio-Tapia, Alberto; Hill, Ivor D; Kelly, Ciarán P; Calderwood, Audrey H; Murray, Joseph A
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
Nadhem, Omar N; Azeez, Ghassan; Smalligan, Roger D; Urban, Steven
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%.
... 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 ...
Bertini, Ivano; Calabrò, Antonio; De Carli, Valeria; Luchinat, Claudio; Nepi, Stefano; Porfirio, Berardino; Renzi, Daniela; Saccenti, Edoardo; Tenori, Leonardo
Celiac disease (CD) is a multifactorial disorder involving genetic and environmental factors, thus, having great potential impact on metabolism. This study aims at defining the metabolic signature of CD through Nuclear Magnetic Resonance (NMR) of urine and serum samples of CD patients. Thirty-four CD patients at diagnosis and 34 healthy controls were examined by (1)H NMR of their serum and urine. A CD patients' subgroup was also examined after a gluten-free diet (GFD). Projection to Latent Structures provided data reduction and clustering, and Support Vector Machines provided pattern recognition and classification. The classification accuracy of CD and healthy control groups was 79.7-83.4% for serum and 69.3% for urine. Sera of CD patients were characterized by lower levels (P < 0.01) of several metabolites such as amino acids, lipids, pyruvate and choline, and by higher levels of glucose and 3-hydroxybutyric acid, while urines showed altered levels (P < 0.05) of, among others, indoxyl sulfate, meta-[hydroxyphenyl]propionic acid and phenylacetylglycine. After 12 months of GFD, all but one of the patients were classified as healthy by the same statistical analysis. NMR thus reveals a characteristic metabolic signature of celiac disease. Altered serum levels of glucose and ketonic bodies suggest alterations of energy metabolism, while the urine data point to alterations of gut microbiota. Metabolomics may thus provide further hints on the biochemistry of the disease.
Dos Santos, Stéphanie; Lioté, Frédéric
Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg. The diagnosis is confirmed by positive specific antibody, anti-transglutaminase or anti-endomysium, specific lesions of the small intestine and a response to strict gluten-free diet. The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia. In the absence of risk factor, osteoporosis, in a premenopausal women or in a man less than 55 years, more is if it is severe and refractory to medications, need to rheumatologists on the track of celiac disease in the absence of digestive symptoms. Osteomalacia is related to secondary hypovitaminosis D malabsorption. Supplementation by calcifediol, water-soluble vitamin D, may be indicated. Celiac disease is associated with an autoimmune disease in almost 1/3 of the cases. Knowing these potential associations allows earlier diagnosis in patients whose only manifestation, a concomitant disease. Anemia, chronic fatigue or unexplained polyarthralgia are symptoms associated with celiac disease to look for specific antibodies. The aim of early diagnosis is to prevent the emergence of other systemic disorders and avoid complications such as bone fractures and cancer, especially intestinal lymphoma. Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out, among patients without specific antibodies and without intestinal lesion of celiac disease. This entity is a cause, at
Basso, M S; Luciano, R; Ferretti, F; Muraca, M; Panetta, F; Bracci, F; Ottino, S; Diamanti, A
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.
Schuppan, Detlef; Dennis, Melinda D; Kelly, Ciaran P
Celiac disease (CD) is an inflammatory small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. It is triggered by the gluten proteins of wheat, barley, and rye. All patients express the antigen-presenting molecules human leukocyte antigen-DQ2 (HLA-DQ2) and/or HLA-DQ8, which bind gluten peptides and thus activate destructive intestinal T cells. Patients with untreated CD have circulating IgA autoantibodies to the enzyme tissue transglutaminase (tTG), a component of endomysium. Testing for serum IgA tTG has a high predictive value. Therapy of CD is a lifelong gluten-free diet. Counseling by an expert dietitian and association with a celiac support group are important in helping the patient embark on a healthy gluten-free diet. Current research focuses on non-dietary therapies and treatment of refractory (diet-unresponsive) CD.
Singh, Nishant K; Baker, Brian M
Recognition of antigens by T cell receptors (TCRs) underlies cellular immunity. By comparing how different TCRs recognize the key antigens associated with celiac disease, Petersen et al. (2016), in this issue of Structure, show how celiac antigen properties select immunologically distinct yet structurally and physically compatible TCRs, ultimately driving autoimmunity.
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
Samsel, Anthony; Seneff, Stephanie
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
Mulder, Christopher J; Cardile, Anthony P; Dickert, Judith
The authors describe a unique presentation of celiac disease as multiple non-traumatic fractures in a young male without gastrointestinal complaints. A 29-year-old man presented with back pain and was found to have a non-traumatic compression fracture of the lumbar and thoracic spine on plain X-ray. Dual-energy x-ray absorptiometry (DXA) confirmed osteoporosis at the L3/L4 vertebral bodies. Parathyroid hormone (PTH), calcium, and vitamin D levels were normal. He had no gastrointestinal complaints, but serologic studies were positive to include an elevated gliadin IgA Ab, gliadin IgG Ab, and an elevated tissue transglutaminase IgA Ab. He was treated with a gluten-free diet, calcium, and vitamin D supplementation as well as teriparatide. Follow up bone density showed improvement and has no further fractures to date. Primary care physicians, gastroenterologists, and endocrinologists must have a high index of clinical suspicion for celiac disease in any patient who presents with low bone density regardless of the serum 25-OH vitamin D levels or presence of gastrointestinal complaints.
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
Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.
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.
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
McAllister, Christopher S; Kagnoff, Martin F
Celiac disease is a T cell-mediated autoimmune inflammatory disease of the small intestine that is activated by gluten. The diagnosis of celiac disease is challenging as patients display a wide range of symptoms and some are asymptomatic. A lifelong gluten-free diet is the only currently approved treatment of celiac disease. Although the diet is safe and effective, the compliance rates and patient acceptance vary. Furthermore, many patients treated with a gluten-free diet continue to be mildly to severely symptomatic with persistent histological abnormalities, and a small number of patients develop refractory celiac disease. New therapeutic adjuncts and potential alternatives to the gluten-free diet could improve the treatment options for these patients. Advances in understanding the immunopathogenesis of celiac disease have suggested several types of therapeutic strategies that may augment or supplant the gluten-free diet. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to celiac disease-specific antigen-presenting molecules. Strategies that limit T cell migration to the small intestine or that reestablish mucosal homeostasis and tolerance to gluten antigens are also being explored. Additionally, it is vital to develop new therapeutic options for refractory celiac disease patients. This review highlights therapeutic strategies that may ultimately improve the health and well-being of individuals with celiac disease.
Castillo, Natalia E.; Theethira, Thimmaiah G.; Leffler, Daniel A.
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
Samasca, Gabriel; Bruchental, Manuela; Butnariu, Angela; Pirvan, Alexandru; Andreica, Mariana; Cristea, Victor; Dejica, Doru
Diagnosis of celiac disease in a patient with lactose intolerance has special importance having implications for the treatment of both diseases. The authors present the case of a 2 years old girl, first diagnosed with enterocolitis, but her clinical evolution revealed a complex situation: both celiac disease and secondary lactose intolerance. We present the case as a special situation in clinical pediatric practice that must be taken into account more often.
Bharadia, Lalit; Shivpuri, Deepak
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.
Moheb-Alian, Ali; Forouzesh, Flora; Rostami-Nejad, Mohammad; Rostami, Kamran
As a chronic immune complication, celiac disease has a broad spectrum of clinical manifestations and gluten ingestion as an external trigger will induce the onset of this disease in genetically predisposed individuals. Because of the complex nature of celiac disease and various cascades of immunological pathways, therapies which are tend to target a single pathway or factor, often have unsatisfactory results. Thus, it should be considered that the new emerging area of cellular therapy by targeting multiple pathways may hold the key for treating celiac affected patients with complicated forms of this disease. The aim of this review is to discuss different pathways which are affected by celiac disease and to compare how various strategies, mainly cellular therapies, can regulate these pathways. PMID:28224021
Casella, Giovanni; Viganò, Davide; Romano Settanni, Carlo; Morelli, Olivia; Villanacci, Vincenzo; Baldini, Vittorio; Bassotti, Gabrio
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
Usai, P; Cherchi, M V; Boy, M F; Cogoni, G; Santa Cruz, G; Balestrieri, A
The authors describe two cases of celiac disease that simulated mesangial IgA nephropathy (Berger's disease). In both cases, gluten-free diet rapidly abated the histological and clinical picture, renal as well as intestinal. The authors conclude that all patients with Berger's disease should be tested systematically for antigliadin antibodies of the IgA class with a view to more accurate clinical classification and therapeutic planning.
Petrecca, S; Giammaria, G; Giammaria, A F
Twenty-nine patients (of both sexes aged between 8 and 18 years old) were referred to our attention with a probable history of celiac disease; intestinal biopsy was positive for the said pathology. Biopsies were compared to a second group of 29 age- and sex-matched control subjects not suffering from gastrointestinal diseases and/or disorders of the phosphocalcium metabolism. The aim of the study was to highlight the possible presence, frequency and extent of oral alterations in confirmed celiac subjects in order to evaluate their greater or lesser incidence compared to controls. The results obtained confirm that celiac patients are more likely to manifest oral pathologies.
Paolella, Gaetana; Lepretti, Marilena; Barone, Maria Vittoria; Nanayakkara, Merlin; Di Zenzo, Marina; Sblattero, Daniele; Auricchio, Salvatore; Esposito, Carla; Caputo, Ivana
Type 2 transglutaminase (TG2) has an important pathogenic role in celiac disease (CD), an inflammatory intestinal disease that is caused by the ingestion of gluten-containing cereals. Indeed, TG2 deamidates specific gliadin peptides, thus enhancing their immunogenicity. Moreover, the transamidating activity seems to provoke an autoimmune response, where TG2 is the main autoantigen. Many studies have highlighted a possible pathogenetic role of anti-TG2 antibodies, because they modulate TG2 enzymatic activity and they can interact with cell-surface TG2, triggering a wide range of intracellular responses. Autoantibodies also alter the uptake of the alpha-gliadin peptide 31-43 (p31-43), responsible of the innate immune response in CD, thus partially protecting cells from p31-43 damaging effects in an intestinal cell line. Here, we investigated whether anti-TG2 antibodies protect cells from p31-43-induced damage in a CD model consisting of primary dermal fibroblasts. We found that the antibodies specifically reduced the uptake of p31-43 by fibroblasts derived from healthy subjects but not in those derived from CD patients. Analyses of TG2 expression and enzymatic activity did not reveal any significant difference between fibroblasts from healthy and celiac subjects, suggesting that other features related to TG2 may be responsible of such different behaviors, e.g., trafficking or subcellular distribution. Our findings are in line with the concept that a "celiac cellular phenotype" exists and that TG2 may contribute to this phenotype. Moreover, they suggest that the autoimmune response to TG2, which alone may damage the celiac mucosa, also fails in its protective role in celiac cells.
Edling, Lars; Rathsman, Sandra; Eriksson, Sune; Bohr, Johan
When investigating a patient with suspected celiac disease (CD), several other conditions must be considered, including potential infection with Giardia lamblia. Although giardiasis is rare, its histopathological and serological picture may resemble that of CD. We report the case of a young man with diabetes mellitus and a family history of CD referred to our hospital because of diarrhoea and weight loss. Investigation showed, among other factors, partial villous atrophy in duodenal biopsies and elevated immunoglobulin A antitissue transglutaminase antibodies. The patient was diagnosed with CD and recommended a gluten-free diet. At the same time, faecal tests were conducted, indicating the presence of G. lamblia. The patient was treated and improved, even after discontinuing the gluten-free diet. Subsequent follow-up after 6 months showed total regression of mucosal histopathology and a normal antitissue transglutaminase antibodies level.
Makharia, Govind K
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.
Makharia, Govind K.
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
Cronin, C C; Shanahan, F
Celiac disease (gluten sensitive enteropathy) is a condition affecting the small bowel, characterized by permanent intolerance to dietary gluten, and giving rise to varying degrees of malabsorption and diarrhea. With the advent of sensitive screening tests, the condition is being increasingly diagnosed. Celiac disease is more common in the Irish and in those of Irish descent. Simoons (1978, 1981) hypothesized that the present-day prevalence of celiac disease across Europe is related to the interaction between genetic gradients, largely determined by the advance of agriculture, and historical patterns of cereal ingestion. This essay examines Simoons' hypothesis as it relates to Ireland, reviews the ethnic and genetic mix of those living on the island of Ireland and aspects of Irish dietary history, and considers how these factors may have combined to result in a high frequency of celiac disease.
... People With Celiac Disease Need to Know About Osteoporosis Publication available in: PDF (98 KB) Related Resources ... Management Strategies Resources For Your Information What Is Osteoporosis? Osteoporosis is a condition in which the bones ...
Mostowy, Joanna; Montén, Caroline; Gudjonsdottir, Audur H.; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel
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
Rondonotti, Emanuele; Villa, Federica; Saladino, Valeria; de Franchis, Roberto
Esophagogastroduodenoscopy (EGD) with 3 to 6 biopsies in the descending duodenum is the gold standard for the diagnosis of celiac disease. At the time of the first diagnosis of celiac disease, an extensive evaluation of the small bowel is not recommended. However, video capsule endoscopy, because of its good sensitivity and specificity in recognizing the Endoscopic features of celiac disease, can be considered a valid alternative to EGD in patients unable or unwilling to undergo EGD with biopsies. Capsule endoscopy is also a possible option in selected cases with strong suspicion of celiac disease but negative first-line tests. In evaluating patients with refractory or complicated celiac disease, in whom a complete evaluation of the small bowel is mandatory (at least in refractory celiac disease type II patients) because of the possible presence of complications beyond the reach of conventional endoscopes, both capsule endoscopy and balloon-assisted enteroscopy have been found to be helpful. In these patients, capsule endoscopy offers several advantages: it is well tolerated, it allows inspection of the entire small bowel, and it is able to recognize subtle mucosal changes. However, in this setting, capsule endoscopy should ideally be coupled with imaging techniques that provide important information about the thickness of the wall of the intestine and about extraluminal abnormalities. Although deep enteroscopy (such as balloon enteroscopy) is expensive, time-consuming, and potentially risky in these frail patients, they may have a key role, because they make it possible to take tissue samples from deep in the small intestine.
Uibo, Raivo; Tian, Zhigang; Gershwin, M Eric
Celiac sprue remains a model autoimmune disease for dissection of genetic and environmental influences on disease progression. The 2010 Congress of Autoimmunity included several key sessions devoted to genetics and environment. Several papers from these symposia were selected for in-depth discussion and publication. This issue is devoted to this theme. The goal is not to discuss genetic and environmental interactions, but rather to focus on key elements of diagnosis, the inflammatory response and the mechanisms of autoimmunity.
Uibo, Raivo; Tian, Zhigang; Gershwin, M Eric
Celiac sprue remains a model autoimmune disease for dissection of genetic and environmental influences on disease progression. The 2010 Congress of Autoimmunity included several key sessions devoted to genetics and environment. Several papers from these symposia were selected for in-depth discussion and publication. This issue is devoted to this theme. The goal is not to discuss genetic and environmental interactions, but rather to focus on key elements of diagnosis, the inflammatory response and the mechanisms of autoimmunity. PMID:21317918
Galicka-Latała, Danuta; Zwolińska-Wcisło, Małgorzata; Sosin-Rudnicka, Lucyna; Rozpondek, Piotr
Celiac disease is the status of the autoimmune answer provoked by gluten ingestion in genetically predisposed people. Recently gluten entheropathy was considered as a rare clinical problem in adults. Celiac disease is an autoimmune disorder that can coexist with other diseases, such as diabetes mellitus type 1 (DMID), thyroid gland diseases. The aim of our study was evaluation of the frequency of coexistence of celiac disease with DMID using the level of anti tissue transglutaminase antibodies (IgA- tTG) and mucosal biopsy from the distal part of the duodenum. An attempt was made to estimate the influence of celiac disease on the intensity of clinical symptoms and metabolic balance in patients with DMID. Our study included 109 patients with DMID, aged 18-52 years. The frequency of the incidence of celiac disease in DMID patients was 9.71%. Gastric symptoms, such as diarrhea, abdominal pain were more frequent in patients with villous atrophy in the intestine. Hyperglycemia and problems with glucose balance in the serum were observed. Introduction of the gluten free diet led to improvement quality of life, less frequent hypoglycemic episodes and disappearance of diarrhea, increase of serum iron and decrease of IgA-tTG level in the serum. It is necessary to measure the level of IgA- tTG in patients with DMID. Diagnosis of celiac disease in patients with DMID and its treatment with gluten free diet causes the clinical, histological and biochemical improvement in these patients.
Lauret, Eugenia; Rodrigo, Luis
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
Lauret, Eugenia; Rodrigo, Luis
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.
Dore, Maria Pina; Pes, Giovanni Mario; Rocchi, Chiara; Loria, Maria Francesca; Soro, Sara; Bassotti, Gabrio
Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated.Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous.3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not.Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study.
Celiac disease (CD) is a T-cell mediated immune disease in which gliadin-derived peptides activate lamina propria effector CD4+ T cells. This activation leads to the release of cytokines, compatible with a Th1-like pattern, which play a crucial role in the pathogenesis of CD, controlling many aspects of the inflammatory immune response. Recent studies have shown that a novel subset of effector T cells, characterized by expression of high levels of IL-17A, termed Th17 cells, plays a pathogenic role in CD. While these effector T cell subsets produce proinflammatory cytokines, which cause substantial tissue injury in vivo in CD, recent studies have suggested the existence of additional CD4(+) T cell subsets with suppressor functions. These subsets include type 1 regulatory T cells and CD25(+)CD4(+) regulatory T cells, expressing the master transcription factor Foxp3, which have important implications for disease progression.
Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR
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
Kumar, Vijay; Rajadhyaksha, Manoj; Wortsman, Jacobo
Celiac disease (CD) is an autoimmune disorder induced by gluten intake in genetically susceptible individuals. It is characterized by the presence of serum antibodies to endomysium, reticulin, gliadin, and tissue transglutaminase. The incidence of CD in various autoimmune disorders is increased 10- to 30-fold in comparison to the general population, although in many cases CD is clinically asymptomatic or silent. The identification of such cases with CD is important since it may help in the control of type I diabetes or endocrine functions in general, as well as in the prevention of long-term complications of CD, such as lymphoma. It is believed that CD may predispose an individual to other autoimmune disorders such as type I diabetes, autoimmune thyroid, and other endocrine diseases and that gluten may be a possible trigger. The onset of type I diabetes at an early age in patients with CD, compared to non-CD, and the prevention or delay in onset of diabetes by gluten-free diet in genetically predisposed individuals substantiates this antigen trigger hypothesis. Early identification of CD patients in highly susceptible population may result in the treatment of subclinical CD and improved control of associated disorders. PMID:11427410
Lindfors, Katri; Rauhavirta, Tiina; Stenman, Satumarja; Mäki, Markku; Kaukinen, Katri
In genetically predisposed individuals, dietary gluten in wheat, rye and barley triggers celiac disease, a systemic autoimmune disorder hallmarked by an extensive small-bowel mucosal immune response. The current conception of celiac disease pathogenesis is that it involves components of both innate and adaptive immunity whose activation typically leads to small-bowel villous atrophy with crypt hyperplasia. Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet excluding all wheat-, rye- and barley-containing food products. During the diet, the clinical symptoms improve and the small-bowel mucosal damage recovers, while re-introduction of gluten into the diet leads to re-appearance of the symptoms and deterioration of the small-bowel mucosal architecture. In view of the restricted nature of the diet, alternative treatment is warranted. Improved understanding of the molecular basis of celiac disease has enabled researchers to suggest other therapeutic approaches. Although there is no animal model reproducing all features of celiac disease, the use of in vitro approaches including a variety of cell lines and the celiac patient small-bowel mucosal biopsy organ culture has generated knowledge about pathogenesis of celiac disease. In these culture systems, gluten induces different effects that can be quantified, thus also enabling studies concerning the efficacy of candidate therapeutic compounds for celiac disease. This review describes the intestinal epithelial cell models, celiac patient T-cell lines and clones, as well as the small-bowel mucosal organ culture methods widely used in studies of celiac disease, and summarizes the major findings obtained with these systems.
There has been considerable interest in celiac disease both in specialized and lay audiences during the past two decades, after it was shown to be much more prevalent in general population than previously thought. This disease can have a wide variety of clinical presentations, ranging from a silent form to a full-blown, sometimes severe disease. The diagnosis of celiac disease requires a high degree of suspicion, is fraught with potential pitfalls, and is a very rigorous process, given the protean nature of the disease. Clinicians should perform appropriate serum testing and conclude with the diagnostic gold standard: documenting the hallmark histological findings in a small bowel biopsy. This paper reviews potential causes of celiac disease misdiagnosis.
Catamo, Eulalia; Zupin, Luisa; Segat, Ludovica; Celsi, Fulvio; Crovella, Sergio
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.
Huang, Shi-Qi; Zhang, Na; Zhou, Zi-Xing; Huang, Chui-Can; Zeng, Cheng-Li; Xiao, Di; Guo, Cong-Cong; Han, Ya-Jing; Ye, Xiao-Hong; Ye, Xing-Guang; Ou, Mei-Ling; Zhang, Bao-Huan; Liu, Yang; Zeng, Eddy Y.; Yang, Guang; Jing, Chun-Xia
Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22–1.30) and 1.17 (95% CI: 1.14–1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease. PMID:28208589
Mearin, Fermín; Montoro, Miguel
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.
Caruso, Roberta; Pallone, Francesco; Stasi, Elisa; Romeo, Samanta; Monteleone, Giovanni
Reduced levels of iron, folate, vitamin B12, vitamin D, zinc, and magnesium are common in untreated celiac disease (CD) patients probably due to loss of brush border proteins and enzymes needed for the absorption of these nutrients. In the majority of patients, removal of gluten from the diet leads to histological recovery and normalization of iron, vitamin, and mineral levels. Iron deficiency anemia is the most common extra-intestinal sign of CD and usually resolves with adherence to a gluten-free diet. However, deficiencies of both folate and vitamin B12 may persist in some patients on a gluten-free diet, thus requiring vitamin supplementation to improve subjective health status. Similarly, exclusion of gluten from the diet does not always normalize bone mineral density; in these cases, supplementation of vitamin D and calcium is recommended. Resolution of mucosal inflammation may not be sufficient to abrogate magnesium deficiency. Since gluten-free cereal products have a lower magnesium content as compared with gluten-containing counterparts, a magnesium-enriched diet should be encouraged in CD patients. In this article we discuss the frequency and clinical relevance of nutrient deficiency in CD and whether and when nutrient supplementation is needed.
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
Park, Kt; Harris, Merissa; Khavari, Nasim; Khosla, Chaitan
Patients with celiac disease (CD) are increasingly interconnected through social media, exchanging patient experiences and health-tracking information between individuals through various web-based platforms. Social media represents potentially unique communication interface between gastroenterologists and active social media users - especially young adults and adolescents with celiac disease-regarding adherence to the strict gluten-free diet, gastrointestinal symptoms, and meaningful discussion about disease management. Yet, various social media platforms may be underutilized for research purposes to collect patient-reported outcomes data. In this commentary, we summarize the scientific rationale and potential for future growth of social media in patient-reported outcomes research, focusing on college freshmen with celiac disease as a case study and provide overview of the methodological approach. Finally, we discuss how social media may impact patient care in the future through increasing mobile technology use.
Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto
The association between celiac disease and primary biliary cirrhosis is well established. The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. In celiac disease, immunologically active molecules generated from the cross-linking between tissue transglutaminase and food/bacterial antigens reach the liver through the portal circulation owing to the increased intestinal permeability. A molecular mimicry between bacterial antigens and the pyruvate dehydrogenase E2 component, recognized by antimitochondrial autoantibodies, may have a role in primary biliary cirrhosis pathogenesis. An aberrant intestinal T lymphocyte homing to the liver may contribute to trigger immune hepatic damage. Both celiac disease and primary biliary cirrhosis share several features, including a higher prevalence in females, autoimmune comorbidities and specific autoantibodies. Reciprocal screening for both diseases is recommended, as an early diagnosis with the appropriate treatment can improve the outcome of these patients.
Kumar, Praveen; Mishra, Kirtisudha; Singh, Preeti; Rai, Kiran
The clinical features of severe acute malnutrition (SAM) often overlap with the common manifestations of celiac disease. In this observational pilot study, 76 children fulfilling the case definition of SAM were investigated for celiac disease, tuberculosis and HIV. Celiac disease was diagnosed in 13.1% of SAM children while tuberculosis and HIV were diagnosed in 9.3% and 4%, respectively.
Gluten, a complex protein group in wheat, rye, and barley, causes celiac disease (CD), an autoimmune enteropathy of the small intestine, in genetically susceptible individuals. CD affects about 1% of the general population and causes significant health problems. Adverse inflammatory reactions to gluten are mediated by inappropriate T-cell activation leading to severe damage of the gastrointestinal mucosa, causing atrophy of absorptive surface villi. Gluten peptides bind to the chemokine receptor, CXCR3, and induce release of zonulin, which mediates tight-junction disassembly and subsequent increase in intestinal permeability. Proinflammatory cytokine IL-15 also contributes to the pathology of CD, by driving the expansion of intra-epithelial lymphocytes that damage the epithelium and promote the onset of T-cell lymphomas. There is no cure or treatment for CD, except for avoiding dietary gluten. Current gluten thresholds for food labeling have been established based on the available analytical methods, which show variation in gluten detection and quantification. Also, the clinical heterogeneity of celiac patients poses difficulty in defining clinically acceptable gluten thresholds in gluten-free foods. Presently, there is no bioassay available to measure gluten-induced immunobiological responses. This review focuses on various aspects of CD, and the importance of gluten thresholds and reference material from an immunological perspective.
Kumar, Jitendra; Kumar, Manoj; Pandey, Rajesh; Chauhan, Nar Singh
Proline- and glutamine-rich gluten proteins are one of the major constituents of cereal dietary proteins, which are largely resistant to complete cleavage by the human gastrointestinal (GI) digestive enzymes. Partial digestion of gluten generates approximately 35 amino acids (aa) immunomodulatory peptides which activate T-cell-mediated immune system, followed by immunological inflammation of mucosa leading to the onset of celiac disease (CD). CD is an autoimmune disease associated with HLA-DQ2/DQ8 polymorphism and dysbiosis of gut microbiota. CD is either diagnosed using duodenal mucosal biopsis or serological testing for transglutaminase 2 (TG2) specific antibodies (IgA and IgG). Current therapy for CD management is gluten-free diet, while other therapies like glutenase, probiotics, immunomodulation, jamming of HLA-DQ2, inhibition of TG2, and gluten tolerance aided by gluten tolerizing vaccines are being developed.
Saccone, Gabriele; Berghella, Vincenzo; Sarno, Laura; Maruotti, Giuseppe M; Cetin, Irene; Greco, Luigi; Khashan, Ali S; McCarthy, Fergus; Martinelli, Domenico; Fortunato, Francesca; Martinelli, Pasquale
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
Ferranti, Pasquale; Mamone, Gianfranco; Picariello, Gianluca; Addeo, Francesco
In recent years, scientific research on wheat gluten proteins has followed three main directions aimed at (1) finding relationships between individual genetic alleles coding for gliadins, high or low molecular weight glutenin subunits, and the viscoelastic dough properties of flour-derived products such as pasta and bread; (2) identifying prolamins and derived peptides involved in celiac disease, a pathological condition in which the small intestine of genetically predisposed individuals is reversibly damaged; and (3) developing and validating sensitive and specific methods for detecting trace amounts of gluten proteins in gluten-free foods for celiac disease patients. In this review, the main aspects of current and perspective applications of mass spectrometry and proteomic technologies to the structural characterization of gliadins are presented, with focus on issues related to detection, identification, and quantification of intact gliadins, as well as gliadin-derived peptides relevant to the biochemical, immunological, and toxicological aspects of celiac disease.
Turck, D.; Ythier, H.; Maquet, E.; Deveaux, M.; Marchandise, X.; Farriaux, J.P.; Fontaine, G.
(/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.
Roy, Abhik; Pallai, Michele; Lebwohl, Benjamin; Taylor, Annette K; Green, Peter H
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.
Grande, Elisabetta; Ferranti, Silvia; Gaggiano, Carla; Di Virgilio, Nicola; Vascotto, Marina
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.
van der Pals, Maria; Ivarsson, Anneli; Norström, Fredrik; Högberg, Lotta; Svensson, Johan; Carlsson, Annelie
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.
Rossi, Mauro; Bot, Adrian
The current issue of the International Reviews of Immunology is dedicated entirely to Celiac Disease (CD). Recent development of additional biomarkers and diagnostics resulted in a sharp revision of the prevalence of this condition, with a previously unrecognized subclinical occurrence in the adult population. This was paralleled by groundbreaking progress in understanding its molecular pathogenesis: while gluten-derived peptides activate the innate immunity, post-translationally modified gluten elicits an adaptive immunity. These arms amplify each other, resulting in a self- perpetuating autoimmune condition, influenced by disturbances of the gut flora and mucus chemistry. The process evolves dramatically in a subset of patients with vulnerable immune homeostasis (eg. Treg cells) explaining the progressive, aggravating syndrome in the clinically overt version of CD. In depth understanding of the pathogenesis of CD thus creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.
Sherman, Andrea; Zamulko, Alla
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.
Jackson, Jessica R; Eaton, William W; Cascella, Nicola G; Fasano, Alessio; Kelly, Deanna L
Celiac Disease (CD) is an immune-mediated disease dependent on gluten (a protein present in wheat, rye or barley) that occurs in about 1% of the population and is generally characterized by gastrointestinal complaints. More recently the understanding and knowledge of gluten sensitivity (GS), has emerged as an illness distinct from celiac disease with an estimated prevalence 6 times that of CD. Gluten sensitive people do not have villous atrophy or antibodies that are present in celiac disease, but rather they can test positive for antibodies to gliadin. Both CD and GS may present with a variety of neurologic and psychiatric co-morbidities, however, extraintestinal symptoms may be the prime presentation in those with GS. However, gluten sensitivity remains undertreated and underrecognized as a contributing factor to psychiatric and neurologic manifestations. This review focuses on neurologic and psychiatric manifestations implicated with gluten sensitivity, reviews the emergence of gluten sensitivity distinct from celiac disease, and summarizes the potential mechanisms related to this immune reaction.
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
Arroyo, Hugo A; De Rosa, Susana; Ruggieri, Victor; de Dávila, María T G; Fejerman, Natalio
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.
Villa, Giorgio La; Pantaleo, Pietro; Tarquini, Roberto; Cirami, Lino; Perfetto, Federico; Mancuso, Francesco; Laffi, Giacomo
We reported a female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy, thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet. PMID:12800261
Zamanian Azodi, Mona; Peyvandi, Hassan; Rostami-Nejad, Mohammad; Safaei, Akram; Rostami, Kamran; Vafaee, Reza; Heidari, Mohammadhossein; Hosseini, Mostafa; Zali, Mohammad Reza
Aim: The aim of this study is to investigate the Protein-Protein Interaction Network of Celiac Disease. Background: Celiac disease (CD) is an autoimmune disease with susceptibility of individuals to gluten of wheat, rye and barley. Understanding the molecular mechanisms and involved pathway may lead to the development of drug target discovery. The protein interaction network is one of the supportive fields to discover the pathogenesis biomarkers for celiac disease. Material and methods: In the present study, we collected the articles that focused on the proteomic data in celiac disease. According to the gene expression investigations of these articles, 31 candidate proteins were selected for this study. The networks of related differentially expressed protein were explored using Cytoscape 3.3 and the PPI analysis methods such as MCODE and ClueGO. Results: According to the network analysis Ubiquitin C, Heat shock protein 90kDa alpha (cytosolic and Grp94); class A, B and 1 member, Heat shock 70kDa protein, and protein 5 (glucose-regulated protein, 78kDa), T-complex, Chaperon in containing TCP1; subunit 7 (beta) and subunit 4 (delta) and subunit 2 (beta), have been introduced as hub-bottlnecks proteins. HSP90AA1, MKKS, EZR, HSPA14, APOB and CAD have been determined as seed proteins. Conclusion: Chaperons have a bold presentation in curtail area in network therefore these key proteins beside the other hub-bottlneck proteins may be a suitable candidates biomarker panel for diagnosis, prognosis and treatment processes in celiac disease. PMID:27895852
Cárdenas, Andrés; Kelly, Ciarán P
Celiac sprue, celiac disease, or gluten-sensitive enteropathy, is a malabsorption disorder of the small intestine that occurs after ingestion of wheat gluten in genetically susceptible individuals. This disease is characterized by intestinal malabsorption associated with villous atrophy of the small intestinal mucosa, clinical and histological improvement after adherence to strict gluten free diet, and relapse when gluten is reintroduced. Celiac sprue has a high prevalence in Western Europe and North America where it is estimated to affect 1:120 to 1:300 individuals. The pathogenesis of celiac sprue is related to inappropriate intestinal T-cell activation in HLA-DQ2 positive individuals triggered by antigenic peptides from wheat gluten or prolamins from barley and rye. Although previously thought to be mainly a disease of childhood onset, the diagnosis is increasingly being made in adults. There are a wide variety of presentations, which range from asymptomatic forms to severe diarrhea, weight loss and nutritional deficiencies. Extraintestinal manifestations including anemia, osteopenia or neurological disorders and associated conditions such as diabetes or hypothyroidism are commonly present. The availability of highly sensitive and specific serologic markers has dramatically facilitated the diagnosis of celiac sprue. However, the demonstration of characteristic histological abnormalities in a biopsy specimen of the small intestine remains the mainstay of diagnosis. Treatment consists of life-long avoidance of dietary gluten to control symptoms and to prevent both immediate and long-term complications.
Kergaravat, Silvina V; Beltramino, Luis; Garnero, Nidia; Trotta, Liliana; Wagener, Marta; Fabiano, Silvia N; Pividori, Maria Isabel; Hernandez, Silvia R
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.
Jansen, Henning; Willenborg, Christina; Schlesinger, Sabrina; Ferrario, Paola G; König, Inke R; Erdmann, Jeanette; Samani, Nilesh J; Lieb, Wolfgang; Schunkert, Heribert
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.
Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción
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.
Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción
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
van Bergen, Jeroen; Mulder, Chris J; Mearin, M Luisa; Koning, Frits
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.
Eberman, Lindsey E; Cleary, Michelle A
Objective: To present the case of an elite female volleyball player who complained of diarrhea and fatigue after preseason training. Background: The athlete lost 8.1 kg during the first 20 days of training, and we initially suspected an eating disorder. The sports medicine team interviewed the athlete and found she did not have psychological symptoms indicative of an eating disorder. The results of routine blood tests revealed critically high platelet counts; in conjunction with the physical findings, the athlete was referred to a gastroenterologist. Differential Diagnosis: Our initial suggestion was an eating disorder. Therefore, the differential diagnosis included anorexia athletica, anorexia nervosa, and bulimia nervosa. On referral, the differential diagnosis was anemia, gastrointestinal dysfunction, lymphoma, or bowel adenocarcinoma. Diarrhea, weight loss, and blood test results were suggestive of active celiac disease, and a duodenal biopsy specimen confirmed this diagnosis. Treatment: The athlete was treated with a gluten-free diet, which excludes wheat, barley, and rye. Dietary substitutions were incorporated to maintain adequate caloric intake. Uniqueness: The presence of active celiac disease may not be uncommon. However, elite athletes who face celiac disease present a new challenge for the athletic trainer. The athletic trainer can help guide the athlete in coping with the lifestyle changes associated with a gluten-free diet. Conclusions: One in every 200 to 400 individuals has celiac disease; many of these individuals are asymptomatic and, therefore, their conditions are undiagnosed. Undiagnosed, untreated celiac disease and patients who fail to follow the gluten-free diet increase the risk of further problems. PMID:16404459
Pinto-Sanchez, Maria Ines; Bercik, Premysl; Verdu, Elena F
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.
Hardy, Melinda Y; Tye-Din, Jason A; Stewart, Jessica A; Schmitz, Frederike; Dudek, Nadine L; Hanchapola, Iresha; Purcell, Anthony W; Anderson, Robert P
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.
Abadie, Valérie; Jabri, Bana
Summary Interleukin-15 (IL-15) exerts many biological functions essential for the maintenance and function of multiple cell types. Although its expression is tightly regulated, IL-15 upregulation has been reported in many organ-specific autoimmune disorders. In celiac disease, an intestinal inflammatory disorder driven by gluten exposure, the upregulation of IL-15 expression in the intestinal mucosa has become a hallmark of the disease. Interestingly, because it is overexpressed both in the gut epithelium and in the lamina propria, IL-15 acts on distinct cell types and impacts distinct immune components and pathways to disrupt intestinal immune homeostasis. In this article, we review our current knowledge of the multifaceted roles of IL-15 with regards to the main immunological processes involved in the pathogenesis of celiac disease. PMID:24942692
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.
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
Cupi, Maria Laura; Sarra, Massimiliano; De Nitto, Daniela; Franzè, Eleonora; Marafini, Irene; Monteleone, Ivan; Del Vecchio Blanco, Giovanna; Paoluzi, Omero Alessandro; Di Fusco, Davide; Gentileschi, Paolo; Ortenzi, Angela; Colantoni, Alfredo; Pallone, Francesco; Monteleone, Giovanni
Celiac disease (CD) is a gluten sensitive enteropathy characterized by a marked infiltration of the mucosa with immune cells, over-production of inflammatory cytokines and epithelial cell damage. The factors/mechanisms that sustain and amplify the ongoing mucosal inflammation in CD are not however fully understood. Here, we have examined whether in CD there is a defective clearance of apoptotic cells/bodies, a phenomenon that helps promote tolerogenic signals thus liming pathogenic responses. Accumulation of apoptotic cells and bodies was more pronounced in the epithelial and lamina propria compartments of active CD patients as compared to inactive CD patients and normal controls. Expression of scavenger receptors, which are involved in the clearance of apoptotic cells/bodies, namely thrombospondin (TSP)-1, CD36 and CD61, was significantly reduced in active CD as compared to inactive CD and normal mucosal samples. Consistently, lamina propria mononuclear cells (LPMC) of active CD patients had diminished ability to phagocyte apoptotic cells. Interleukin (IL)-15, IL-21 and interferon-γ, cytokines over-produced in active CD, inhibited the expression of TSP-1, CD36, and CD61 in normal intestinal LPMC. These results indicate that CD-related inflammation is marked by diminished clearance of apoptotic cells/bodies, thus suggesting a role for such a defect in the ongoing mucosal inflammation in this disorder.
Cupi, Maria Laura; Sarra, Massimiliano; De Nitto, Daniela; Franzè, Eleonora; Marafini, Irene; Monteleone, Ivan; Del Vecchio Blanco, Giovanna; Paoluzi, Omero Alessandro; Di Fusco, Davide; Gentileschi, Paolo; Ortenzi, Angela; Colantoni, Alfredo; Pallone, Francesco; Monteleone, Giovanni
Celiac disease (CD) is a gluten sensitive enteropathy characterized by a marked infiltration of the mucosa with immune cells, over-production of inflammatory cytokines and epithelial cell damage. The factors/mechanisms that sustain and amplify the ongoing mucosal inflammation in CD are not however fully understood. Here, we have examined whether in CD there is a defective clearance of apoptotic cells/bodies, a phenomenon that helps promote tolerogenic signals thus liming pathogenic responses. Accumulation of apoptotic cells and bodies was more pronounced in the epithelial and lamina propria compartments of active CD patients as compared to inactive CD patients and normal controls. Expression of scavenger receptors, which are involved in the clearance of apoptotic cells/bodies, namely thrombospondin (TSP)-1, CD36 and CD61, was significantly reduced in active CD as compared to inactive CD and normal mucosal samples. Consistently, lamina propria mononuclear cells (LPMC) of active CD patients had diminished ability to phagocyte apoptotic cells. Interleukin (IL)-15, IL-21 and interferon-γ, cytokines over-produced in active CD, inhibited the expression of TSP-1, CD36, and CD61 in normal intestinal LPMC. These results indicate that CD-related inflammation is marked by diminished clearance of apoptotic cells/bodies, thus suggesting a role for such a defect in the ongoing mucosal inflammation in this disorder. PMID:24971453
Escudero-Hernández, Celia; Peña, Amado Salvador; Bernardo, David
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.
Alventosa Mateu, Carlos; Larrey Ruiz, Laura; Pérez Zahonero, Maria Dolores; Navarro Gonzales, Atilio Javier; Canelles Gamir, Pilar; Huguet Malavés, José María; Luján Sanchís, María Soledad; Martorell Cebollada, Miguel Ángel; Medina Chuliá, Enrique
Collagenous sprue is a rare disease that goes with persistent diarrhea, weight loss and bad absortion, because it affects the small intestine, mainly duodenum and proximal jejunum. Diagnosis is made by having clinical signs and histological proof of atrophy and subepitelial deposit of collagenous material. Its etiology is not known completely, it is proposed that the origin is autoimmune because its relationship with celiac disease. Also there is a proposal that is a celiac evolution to gluten free diet. Is because this is not clear that we present a case of a patient with bad absorptive diarrhea and a clinical expression of collagenous sprue, that had a great clinical response to corticosteroids with home parenteral nutrition center.
Agarwal, Shreya; Kovilam, Oormila; Zach, Terence L; Agrawal, Devendra K
Celiac Disease is an autoimmune enteropathy with increasing incidence worldwide in both adults and children. It occurs as an inflammatory condition with destruction of the normal architecture of villi on consumption of gluten and related protein products found in wheat, barley and rye. However, the exact pathogenesis is not yet fully understood. A gluten-free diet remains the main modality of therapy to date. While some patients continue to have symptoms even on a gluten-free diet, adherence to this diet is also difficult, especially for the children. Hence, there is continued interest in novel methods of therapy and the current research focus is on the promising novel non-dietary modalities of treatment. Here, we critically reviewed the existing literature regarding the pathogenesis of celiac disease in children including the role of in-utero exposure leading to neonatal and infant sensitization and its application for the development of new therapeutic approaches for these patients.
Kim, Sangman Michael; Mayassi, Toufic; Jabri, Bana
Celiac disease is a T cell mediated immune disorder characterized by the loss of oral tolerance to dietary gluten and the licensing of intraepithelial lymphocytes to kill intestinal epithelial cells, leading to villous atrophy. Innate immunity plays a critical role in both of these processes and cytokines such as interleukin-15 and interferon-α can modulate innate processes such as polarization of dendritic cells as well as intraepithelial lymphocyte function. These cytokines can be modulated by host microbiota, which can also influence dendritic cell function and intraepithelial lymphocyte homeostasis. We will elaborate on the role of interleukin-15, interferon-α, and the microbiota in modulating the processes that lead to loss of tolerance to gluten and tissue destruction in celiac disease.
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Eid, Wael E
Hypovitaminosis D and its consequences are significant complications in the course of untreated celiac disease (CD). We report a case that illustrates the natural evolution of osteomalacia in an adult patient with untreated CD and his response to vitamin D supplementation. In patients with complicated CD and hypovitaminosis D, vitamin D-2 replacement in high enough doses is important to improving functional performance and for the treatment of osteomalacia.
Ciccocioppo, Rachele; Kruzliak, Peter; Cangemi, Giuseppina C.; Pohanka, Miroslav; Betti, Elena; Lauret, Eugenia; Rodrigo, Luis
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
Rashid, Mohsin; Butzner, Decker; Burrows, Vernon; Zarkadas, Marion; Case, Shelley; Molloy, Mavis; Warren, Ralph; Pulido, Olga; Switzer, Connie
The treatment of celiac disease is a strict adherence to a gluten-free diet for life. In the past, oats were considered to be toxic to individuals with celiac disease and were not allowed in a gluten-free diet. However, recent evidence suggests that oats that are pure and uncontaminated with other gluten-containing grains, if taken in limited quantities, are safe for most individuals with celiac disease. For adults, up to 70 g (1/2 to 3/4 cup) of oats per day and for children, up to 25 g (1/4 cup) per day are safe to consume. These oats and oat products must fulfill the standards for a gluten-free diet set by the Canadian Food Inspection Agency and Health Canada. The Canadian Celiac Association, in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats. These strategies have led to the production of pure, uncontaminated oats for the first time in Canada. Oats and oat products that are safe for consumption by individuals with celiac disease and dermatitis herpetiformis are now commercially available in Canada.
De Re, Valli; Caggiari, Laura; Tabuso, Maria; Cannizzaro, Renato
The link between the gluten component of wheat and celiac disease (CD) was discovered in 1952 by a team of physicians from Birmingham, England. Villous atrophy was described by John W. Paulley in 1954. During the 1960s, other features of CD were elucidated; its hereditary nature was recognized in 1965, and in 1966, dermatitis herpetiformis was linked to gluten sensitivity. Following the discovery of a link between gluten and CD, it was demonstrated that gliadin, one of the two principal protein groups comprising gluten, plays a critical role in CD. It has since become clear that the different and crucial roles of gliadin in CD result from its ability to activate multiple signaling pathways that modulate CD pathology. Most of these pathways involve the host innate and adaptive immune responses, but some pathways are activated when gliadin interacts with the intestinal cellular compartment. This review covers the current knowledge of the role of gliadin peptides in CD disorders that are characterized by intraepithelial T-cells infiltration (IEL), production of autoantibodies, endosomal trafficking, alteration of intestinal barrier function and intestinal cell proliferation. In addition, it examines the ability of these characteristics to determine the main clinicopathological features of gluten sensitivity for the purpose of identifying new strategies, other than maintaining a gluten-free diet, to improve the management of CD patients in the future.
Kelly, Ciarán P.; Bai, Julio C.; Liu, Edwin; Leffler, Daniel A.
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
Rostami Nejad, M; Rostami, K; Emami, MH; Zali, MR; Malekzadeh, R
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
Rostami Nejad, M; Rostami, K; Emami, Mh; Zali, Mr; Malekzadeh, R
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.
Mocan, Oana; Dumitraşcu, Dan L
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.
MOCAN, OANA; DUMITRAŞCU, DAN L.
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
Cabrera-Chávez, Francisco; de la Barca, Ana María Calderón
Celiac disease is an autoimmune disease triggered mainly by ingestion of wheat gluten proteins. However, some other dietary proteins, such as those of cow's milk, induce celiac disease-like symptoms in some patients with celiac disease. Different approaches have been done to detect the component responsible for this problem, including the possibility of gluten peptides present in cow's milk.
Lerner, Aaron; Matthias, Torsten
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.
Rajpoot, Preeti; Makharia, Govind K
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.
Utiyama, Shirley Ramos da Rosa; Ribas, João Luis Coelho; Nisihara, Renato Mitsunori; Kotze, Lorete Maria da Silva; de Messias-Reason, Iara José
Background: Celiac disease has been described in populations from around the world, with recent data emphasizing the occurrence of the disease in ethnic minorities. There are only a few studies evaluating celiac disease in native Indians. Aims: This study aimed to screen the anti-endomysial antibody (IgA-EmA) in Kaingang and Guarani Indians from southern Brazil, in order to establish a clinical serological evaluation of celiac disease in these individuals. Material and Methods: Serum samples from 321 individuals (125 male and 196 female; 4-86 years old) from Mangueirinha Indigenous Reserve, State of Parana, Brazil, and 180 non-Indigenous healthy individuals (62 male and 118 female; 2-81 years old) were analysed to the presence of anti-endomysial antibody class IgA by indirect immunofluorescence assay. Amongst the Indians, 158 were Kaingang, 98 Guarani and 65 of mixed race. Indians presenting complaints of diarrhea (N=12) were also evaluated to the IgG class of anti-endomisyal antibody. Results: None of the individuals showed positive results either to IgA or IgG anti-endomysial antibodies. Conclusions: Although the results indicate an absence of celiac disease in Kaingang and Guarani Indians, the authors call attention to the importance of following up indigenous children or adults presenting gastrointestinal complaints or other symptoms related to the disease. Consideration should be given to the genetic background of these individuals, allied to the inter ethnic marriages and the changing habits or occupational activities, that have gradually introduced diseases previously not described in indigenous populations. PMID:22624128
Matoori, Simon; Fuhrmann, Gregor; Leroux, Jean-Christophe
Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten's omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a gluten-free diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with CD.
Pulido, Olga M; Gillespie, Zoe; Zarkadas, Marion; Dubois, Sheila; Vavasour, Elizabeth; Rashid, Mohsin; Switzer, Connie; Godefroy, Samuel Benrejeb
Celiac disease is an immune-mediated disease, triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. The only treatment for celiac disease is a strict gluten-free diet for life. This paper presents a systematic review of the scientific literature on the safety of pure oats for individuals with celiac disease, which historically has been subject to debate. Limitations identified within the scientific database include: limited data on long-term consumption, limited numbers of participants in challenge studies, and limited reporting about the reasons for withdrawals from study protocols. Furthermore, some evidence suggests that a small number of individuals with celiac disease may be intolerant to pure oats and some evidence from in vitro studies suggests that an immunological response to oat avenins can occur in the absence of clinical manifestations of celiac disease as well as suggesting that oat cultivars vary in toxicity. Based on the majority of the evidence provided in the scientific database, and despite the limitations, Health Canada and the Canadian Celiac Association (CCA) concluded that the majority of people with celiac disease can tolerate moderate amounts of pure oats. The incorporation of oats into a gluten-free diet provides high fiber and vitamin B content, increased palatability, and beneficial effects on cardiovascular health. However, it is recommended that individuals with celiac disease should have both initial and long-term assessments by a health professional when introducing pure oats into a gluten-free diet.
Rubio-Tapia, Alberto; Hill, Ivor D; Kelly, Ciarán P; Calderwood, Audrey H; Murray, Joseph A
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
Sezer, Taner; Balcı, Oya; Özçay, Figen; Bayraktar, Nilufer; Alehan, Füsun
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.
Silano, Marco; Vincentini, Olimpia; De Vincenzi, Massimo
Celiac disease (CD) is an increasingly diagnosed, permanent autoimmune enteropathy, triggered, in susceptible individuals, by the ingestion of gluten, the alcohol - soluble protein fraction of some cereals, such as wheat, rye and barley. The main protein of wheat gluten is called gliadin, the similar proteins of rye and barley are secalin and hordein, respectively. Approximately 96% of CD patients express the HLA molecule DQ2, while the remainder mostly express the less common haplotype DQ8, reflecting the pivotal role of these molecules in the pathogenesis of CD. Because of their aminoacid sequence and tri-dimensional structure, gluten peptides selectively bind to these HLA alleles present on the surface of antigen presenting cells and then they are presented to the T lymphocytes in intestinal mucosa, thus starting the inflammatory immune response. CD is defined by the characteristic histological changes of small bowel mucosa: villous atrophy, crypts hyperplasia and T cells infiltration of the lamina propria, along with the increase of the number of intra-epithelial lymphocytes. The withdrawal of the gluten- containing food from the diet determines a complete recovery of the intestinal mucosa, whereas the reintroduction causes a relapse of the disease. This review focuses on the description of gluten peptides that elicit the mucosal immune response via the activation of innate and adaptive immunity in CD. It also describes the antagonist gluten peptides, obtained by artificial modification of gluten T epitopes or naturally occurring in the alcohol protein fraction of a cultivar of durum wheat, able to immuno-modulate the pathogenic immune response of CD.
Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.
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
This is a selective review of the literature concerning the methods of celiac disease treatment, which can be an alternative to a gluten-free diet. The most advanced studies are devoted to the larazotide acetate (AT-1001, human zonulin inhibitor) and prolyl-endopeptidases degrading toxic gluten peptides (ALV003, AN-PEP). It is estimated that they will be registered within a few years. They will not become an alternative to the gluten-free diet but rather a supplement to it, which will enable patients to ease the nutritional restrictions. PMID:25960809
Sabel'nikova, E A
The prevalence of celiac disease is about 1% in the population and is growing due to the wide use of immunological methods of diagnosis. In recent years, in-depth research of the celiac disease has led not only to an increase in the number of patients with celiac disease, but also to the emergence of a broad spectrum of diseases associated with the ingestion of gluten. In this regard, a new pathology, known as "gluten intolerance or gluten sensitivity", attracted special attention of researchers. Studies in recent years have established that patients with this pathology may have both gastrointestinal symptoms and extraintestinal manifestations. Examinations of such patients usually do not find histological changes of the mucous membrane of the small intestine and autoimmune antibodies (to tissue transglutaminase (tTG) and endomysial (EMA)); however an increased level of gliadin antibodies (AGA) is often observed. Allergy to gluten is also absent. A gluten-free diet for such patients, like in case of the celiac disease, leads to the disappearance of clinical symptoms. Exact criteria for the diagnosis of this nosology have not been identified so far, but most researchers believe that prevalence of "gluten intolerance" is much higher than that of celiac disease.
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Peräaho, Markku; Collin, Pekka; Kaukinen, Katri; Kekkonen, Leila; Miettinen, Sanna; Mäki, Markku
Finnish celiac disease and dermatitis herpetiformis patients have used oat-containing gluten-free diets since 1997. The aim of this study was to evaluate how the use of oats has been adopted. The use of oats and the effect of oats on symptoms and quality of life were investigated in 1,000 randomly selected members of the Celiac Society. Altogether, 710 patients responded: 423 (73%) with celiac disease and 70 (55%) with dermatitis herpetiformis were currently consuming oats. Patients appreciated the taste, the ease of use, and the low costs; 94% believed that oats diversified the gluten-free diet; 15% of celiac disease and 28% of dermatitis herpetiformis patients had stopped eating oats. The most common reasons for avoiding oats were fear of adverse effects or contamination. There is a market demand for oats, and celiac societies and dietitians should make efforts to promote the development of products free of wheat contamination.
Rostami Nejad, Mohammad; Ishaq, Sauid; Al Dulaimi, David; Zali, Mohammad Reza; Rostami, Kamran
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.
Qiao, Shuo-Wang; Ráki, Melinda; Gunnarsen, Kristin S; Løset, Geir-Åge; Lundin, Knut E A; Sandlie, Inger; Sollid, Ludvig M
Posttranslational modification of Ag is implicated in several autoimmune diseases. In celiac disease, a cereal gluten-induced enteropathy with several autoimmune features, T cell recognition of the gluten Ag is heavily dependent on the posttranslational conversion of Gln to Glu residues. Evidence suggests that the enhanced recognition of deamidated gluten peptides results from improved peptide binding to the MHC and TCR interaction with the peptide-MHC complex. In this study, we report that there is a biased usage of TCR Vβ6.7 chain among TCRs reactive to the immunodominant DQ2-α-II gliadin epitope. We isolated Vβ6.7 and DQ2-αII tetramer-positive CD4(+) T cells from peripheral blood of gluten-challenged celiac patients and sequenced the TCRs of a large number of single T cells. TCR sequence analysis revealed in vivo clonal expansion, convergent recombination, semipublic response, and the notable conservation of a non-germline-encoded Arg residue in the CDR3β loop. Functional testing of a prototype DQ2-α-II-reactive TCR by analysis of TCR transfectants and soluble single-chain TCRs indicate that the deamidated residue in the DQ2-α-II peptide poses constraints on the TCR structure in which the conserved Arg residue is a critical element. The findings have implications for understanding T cell responses to posttranslationally modified Ags.
Vitaliti, Giovanna; Praticò, Andrea Domenico; Cimino, Carla; Di Dio, Giovanna; Lionetti, Elena; La Rosa, Mario; Leonardi, Salvatore
Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.
El-Hodhod, Mostafa Abdel-Aziz; El-Agouza, Iman Ali; Abdel-Al, Hala; Kabil, Noha Samir; Bayomi, Khaled Abd El-Moez
Background. Dental enamel defects (DEDs) are seen in celiac disease (CD). Aim was to detect frequency of CD among such patients. Methods. This study included 140 children with DED. They were tested for CD. Gluten-free diet (GFD) was instituted for CD patients. A cohort of 720, age and sex-matched, normal children represented a control group. Both groups were evaluated clinically. Serum calcium, phosphorus, alkaline phosphatase, serum IgA, and tissue transglutaminase (tTG) IgG and IgA types were measured. Results. CD was more diagnosed in patients with DEDs (17.86%) compared to controls (0.97%) (P < 0.0001). Majority of nonceliac patients showed grade 1 DED compared to grades 1, 2, and 3 DED in CD. Five children had DED of deciduous teeth and remaining in permanent ones. After 1 year on GFD, DED improved better in CD compared to nonceliac patients. Gastrointestinal symptoms did not vary between celiac and nonceliac DED patients. Lower serum calcium significantly predicted CD in this cohort. Conclusion. CD is more prevalent among children with DED than in the general population. These DEDs might be the only manifestation of CD; therefore, screening for CD is highly recommended among those patients especially in presence of underweight and hypocalcemia. PMID:22720168
Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro
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.
Socorro, A. B.; Corres, J. M.; Del Villar, I.; Matias, I. R.; Arregui, F. J.
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.
Merra, Giuseppe; Lago, Antonio Dal; Roccarina, Davide; Gasbarrini, Giovanni; Gasbarrini, Antonio; Ghirlanda, Giovanni
Celiac disease (CD) is an autoimmune disorder of the small bowel that occurs in genetically predisposed people of all ages, from middle infancy, and is caused by a reaction to gliadin, a gluten protein. Some patients are diagnosed with symptoms related to the decreased absorption of nutrients or with various symptoms which, although statistically linked, have no clear relationship with the malfunctioning bowel. Classic symptoms of CD include diarrhea, weight loss, and fatigue; bowel symptoms may be limited or even absent. In this article we describe the case of a young woman with CD who presents with myointimal proliferation. However multiple cases of vessel thrombosis have been reported in patients with CD. Despite the fact that no definitive relationship between these diseases could be explained, we think this association must be remembered especially in cases of young and tenuous women with these vascular abnormalities. PMID:21897789
Danus, O; Larraín, F; Urbina, A M
A review of 81 children with celiac disease over a period of 5 years is presented. These cases were seen at the Gastroenterological Unit of the Hospital de Nińos Roberto del Río, during years 1970 through 1972. 62% of the patients (50) were placed under control of their disease, the rest were studied and diagnosed only for other centers. The short term evolution was good in 48 children (96%), while the medium and long term evolution, 2 to 5 years, was good only in 56% of the patients. This evolution was in direct relationship to the fulfillment of the dietary indications. The therapeutic test was positive among the studied group. A delay was observed in 80% of the cases that lasted from 1 to 6 months. The clinical and laboratory features of the group are analyzed, and the working method is described.
Buoli Comani, Gaia; Panceri, Roberto; Dinelli, Marco; Biondi, Andrea; Mancuso, Clara; Meneveri, Raffaella; Barisani, Donatella
Celiac disease is an intestinal disease which shows different symptoms and clinical manifestations among pediatric and adult patients. These variations could be imputable to age-related changes in gut architecture and intestinal immune system, which could be characterized by gene expression differences possibly regulated by miRNAs. We analyzed a panel of miRNAs and their target genes in duodenal biopsies of Marsh 3AB and 3C pediatric celiac patients, compared to controls. Moreover, to assess variation of expression in plasma samples, we evaluated circulating miRNA levels in controls and patients at diagnosis or on gluten-free diet. We detected a decreased miR-192-5p expression in celiac patients, but no variations in NOD2 and CXCL2, targets previously identified in adults. Conversely, we detected a significant increase in mRNA and protein levels of another target, MAD2L1, protein related to cell cycle control. miR-31-5p and miR-338-3p were down-regulated and their respective targets, FOXP3 and RUNX1, involved in Treg function, resulted up-regulated in celiac patients. Finally, we detected, in celiac patients, an increased expression of miR-21-5p, possibly caused by a regulatory loop with its putative target STAT3, which showed an increased activation in Marsh 3C patients. The analysis of plasma revealed a trend similar to that observed in biopsies, but in presence of gluten-free diet we could not detect circulating miRNAs values comparable to controls. miRNAs and their gene targets showed an altered expression in duodenal mucosa and plasma of celiac disease pediatric patients, and these alterations could be different from adult ones.
Tuhan, Hale; Işık, Sakine; Abacı, Ayhan; Şimşek, Erdem; Anık, Ahmet; Anal, Özden; Böber, Ece
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
Collin, Pekka; Reunala, Timo
In celiac disease, the ingestion of gluten-containing cereals, such as wheat, rye, and barley, results in small-bowel mucosal inflammation and villous atrophy with crypt hyperplasia. The prevalence of the condition may be as high as 1% in the adult population. The disease can also embrace various extraintestinal manifestations, of which dermatitis herpetiformis is the best known. Earlier, dermatitis herpetiformis was considered a skin disease occurring often concomitantly with celiac disease. At present, a body of evidence shows that dermatitis herpetiformis is a cutaneous manifestation of celiac disease, and affects approximately 25% of patients with celiac disease. Both conditions can appear in the same family and are closely linked to HLA class II locus in chromosome 6; 90% of patients have HLA DQ2 and, almost all the remainder, HLA DQ8. All patients with dermatitis herpetiformis have at least some-degree of mucosal inflammation or lesion consistent with celiac disease. The etiology of celiac disease in not fully understood, but tissue transglutaminase seems to be the predominant autoantigen both in the intestine and the skin. Serum antibodies against tissue transglutaminase can be used in the serologic screening and follow-up of dietary compliance of patients with celiac disease. Gluten-free diet is essential in the treatment of both conditions, and oral dapsone is usually needed in newly detected dermatitis herpetiformis in order to alleviate symptoms. Oral mucosal lesions, alopecia areata, and vitiligo probably occur more frequently in patients with dermatitis herpetiformis than in the general population. By contrast, the reported association of celiac disease with psoriasis seems to be coincidental.
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.
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
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.
Abenavoli, L; Delibasic, M; Peta, V; Turkulov, V; De Lorenzo, A; Medić-Stojanoska, M
Celiac disease (CD) is a chronic immune-mediated gluten dependent enteropathy induced by ingestion of gluten, characterized by intestinal malabsorption and subtotals or total atrophy of intestinal villi. The predominant consequence of CD in untreated patients, is malnutrition as a result of malabsorption. Moreover, several and increasing extra-intestinal clinical manifestations have been described in the CD patients. Strict adherence to a gluten-free diet (GFD) improves nutritional status, inducing an increase in fat and bone compartments, but does not completely normalize body composition and nutritional deficiencies. An early and accurate evaluation of nutritional status can be of the pivotal step in the clinical management of the adult CD patients. The aim of this review is to present the most important and recent data on nutritional and metabolic features in the CD adult patients, the related implications and the effects of the GFD on these conditions.
Newton, Kimberly P; Singer, Shereen A
Although there are many commonalities between adult and pediatric celiac disease (CD), special considerations must be taken into account when working with children and adolescents. In this patient population, there are unique aspects of the epidemiology, pathogenesis, presentation, diagnosis, and management of CD. In terms of management, early and timely recognition of CD can maximize childhood and adolescent development and prevent complications. This requires insight into the unique presentations of CD in the pediatric population. Furthermore, health care providers must use proper screening methods and continue surveillance of at-risk individuals throughout childhood. Potential interventions for primary prevention of CD in children, although not completely understood, may offer some benefit. The goals of this article are to discuss in detail these special considerations when dealing with pediatric CD.
Celiac disease (CD) is an intestinal disorder caused by an intolerance to gluten, proteins in wheat. CD is an HLA-associated disease: virtually all patients express HLA-DQ2 or HLA-DQ8. Recent work has shown that these disease-predisposing HLA-DQ molecules bind enzymatically modified gluten peptides and these HLA-DQ peptide complexes trigger inflammatory T-cell responses in the small intestine that lead to disease. In addition, gluten induces innate immune responses that contribute to the tissue damage that is characteristic for CD. Thus, CD patients are caught between a rock and a hard place: the disease is caused by a combination of adaptive and innate immune responses that both are triggered by gluten. These findings explain the disease-inducing properties of gluten and provide valuable clues for the development of alternative treatment modalities for patients. They also may be of relevance for our understanding of other multifactorial disorders including IBD and HLA-associated autoimmune diseases.
Mitea, Cristina; Salentijn, Elma M J; van Veelen, Peter; Goryunova, Svetlana V; van der Meer, Ingrid M; van den Broeck, Hetty C; Mujico, Jorge R; Montserrat, Veronica; Monserrat, Veronica; Gilissen, Luud J W J; Drijfhout, Jan Wouter; Dekking, Liesbeth; Koning, Frits; Smulders, Marinus J M
Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the α-gliadins. It has been shown that α-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from α-gliadins. We have analyzed over 3,000 expressed α-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived α-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the α-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations α-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients.
Ouseph, Madhu M.; Simons, Malorie; Treaba, Diana O.; Yakirevich, Evgeny; Green, Peter H.; Bhagat, Govind; Moss, Steven F.
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
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
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
Caruso, C; Candore, G; Lio, D; Modica, M A; Cataldo, F; Maltese, I; Marino, V; Albeggiani, A
We studied the role of the immunoglobulin heavy-chain allotypes in the evolution of celiac disease. Particularly the Gm(fb) phenotype was investigated since this phenotype is able to determine the breadth of immune response against alpha-gliadin antigen. The results show that weight percentiles and intestinal absorption as assessed by xylose test are influenced by Gm(fb) phenotype suggesting that Gm(fb) genes contribute to the determination of clinical aspects and evolution of celiac disease.
Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo Lucca
Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress. PMID:28223722
Dehghani, Seyed Mohsen; Ehsaei, Zahra; Honar, Naser; Javaherizadeh, Hazhir
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.
Sdepanian, V L; de Morais, M B; Fagundes Neto, U
In the recent past, some celiac disease features have been discussed in literature specially related to genetic susceptibility, pathogenesis, clinical presentation and diagnostic criteria. Immunological abnormalities characteristic of celiac disease, such as circulating antibodies and increased numbers of intra-epithelial lymphocytes containing a high percentage of gamma-delta T cells have been demonstrated. Other pictures of clinical presentation besides the classical one deserve attention namely short stature, iron-resistant anaemia, enamel hypoplasia, constipation, neurological manifestation and osteoporosis, among others. Asymptomatic presentation has been recognized since development of serological markers such as anti-gliadin, anti-reticulin and anti-endomysium antibodies. Up to now, small intestinal biopsy is the only decisive diagnostic approach. A Federal law has recently imposed food manufactures to place labels informing the presence of gluten in industrialized foods in Brazil. Lately there has been an increase in celiac disease patients registered in the Brazilian Celiac Association.
Lebwohl, Benjamin; Murray, Joseph A; Verdú, Elena F; Crowe, Sheila E; Dennis, Melinda; Fasano, Alessio; Green, Peter H R; Guandalini, Stefano; Khosla, Chaitan
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.
Among the adverse reactions caused by wheat, celiac disease (CD) is the longest studied and best-known pathology. The more recently defined non-celiac gluten sensitivity (NCGS) presents with symptoms which are often indistinguishable from CD. Diagnosis of CD is based on serologic, molecular, and bioptic testing. The IgA anti-transglutaminase (tTG) test is considered highly important, as it shows high sensitivity and specificity and its levels correlate to the degree of intestinal damage. Small bowel biopsy can be avoided in symptomatic patients with IgA anti-tTG levels above 10× the manufacturer's cut-off. Recently, tests of anti-deamidated peptides of gliadin (DGP) have replaced classic anti-native gliadin (AGA) tests. DGP assays have a considerably higher diagnostic accuracy than AGA assays, especially in the IgG class, and can replace anti-tTG tests in patients with selective IgA deficiency. The combination of IgG anti-DGP plus IgA anti-tTG assays show greater sensitivity than a single test, with very high specificity. EMA tests have great diagnostic accuracy but are not recommended by all the latest guidelines because they are observer dependent. Biopsy must still be considered the gold standard for CD diagnosis. HLA-DQ genotyping can be used to screen asymptomatic children and in cases of histology/serology disagreement. About half of NCGS patients are DQ2 positive and have IgG AGA. To diagnose NCGS, first CD and wheat allergy must be excluded; then the wheat dependence of symptoms must be verified by a gluten-free diet and subsequent gluten challenge.
Dydensborg Sander, Stine; Størdal, Ketil; Plato Hansen, Tine; Nybo Andersen, Anne-Marie; Murray, Joseph A; Lillevang, Søren Thue; Husby, Steffen
Purpose The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. Patients and methods We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. Results We identified 2,247 children who were registered in the Danish National Patient Register with celiac disease. Duodenal biopsies for 1,555 of the children (69%) were registered in the Patobank; 1,127 (50%) had a biopsy that was compatible with celiac disease (ie, Marsh 2–3). We accessed the medical records of 95% of the children who were registered in the Danish National Patient Register with celiac disease. We found that 1,510 (67%) had one or more positive antibody-test results; 1,120 (50%) had anti-tissue transglutaminase 2, IgA at tenfold or greater the upper limit of the normal range and/or positive endomysial antibody results. The positive predictive value depended on the criteria used for validation and the types and numbers of registrations that were included in the analysis and ranged from 62% (95% confidence interval: 60%–64%) to 86% (95% confidence interval: 84%–87%). Conclusion Our findings indicate that the Danish National Patient Register is a valuable source to identify patients who have been diagnosed with celiac disease. However, validation of the diagnoses is warranted before data on the
Lerner, Aaron; Matthias, Torsten
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.
La Vieille, Sébastien; Pulido, Olga M; Abbott, Michael; Koerner, Terence B; Godefroy, Samuel
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.
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
Isaac, Daniela Migliarese; Wu, Jessica; Mager, Diana R; Turner, Justine M
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.
Pozo-Rubio, Tamara; Olivares, Marta; Nova, Esther; De Palma, Giada; Mujico, Jorge R.; Ferrer, Maria Desamparados; Marcos, Ascensión; Sanz, Yolanda
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
Isaac, Daniela Migliarese; Wu, Jessica; Mager, Diana R; Turner, Justine M
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
Medrano, Luz María; García-Magariños, Manuel; Dema, Bárbara; Espino, Laura; Maluenda, Carlos; Polanco, Isabel; Figueredo, M. Ángeles; Fernández-Arquero, Miguel; Núñez, Concepción
Th17 cells are known to be involved in several autoimmune or inflammatory diseases. In celiac disease (CD), recent studies suggest an implication of those cells in disease pathogenesis. We aimed at studying the role of genes relevant for the Th17 immune response in CD susceptibility. A total of 101 single nucleotide polymorphisms (SNPs), mainly selected to cover most of the variability present in 16 Th17-related genes (IL23R, RORC, IL6R, IL17A, IL17F, CCR6, IL6, JAK2, TNFSF15, IL23A, IL22, STAT3, TBX21, SOCS3, IL12RB1 and IL17RA), were genotyped in 735 CD patients and 549 ethnically matched healthy controls. Case-control comparisons for each SNP and for the haplotypes resulting from the SNPs studied in each gene were performed using chi-square tests. Gene-gene interactions were also evaluated following different methodological approaches. No significant results emerged after performing the appropriate statistical corrections. Our results seem to discard a relevant role of Th17 cells on CD risk. PMID:22359581
Chick, Kay A.
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…
Taghdir, Maryam; Honar, Naser; Mazloomi, Seyed Mohammad; Sepandi, Mojtaba; Ashourpour, Mahkameh; Salehi, Musa
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
Doğan, Murat; Peker, Erdal; Cagan, Eren; Akbayram, Sinan; Acikgoz, Mehmet; Caksen, Huseyin; Uner, Abdurrahman; Cesur, Yasar
Celiac disease (CD) is manifested by a variety of clinical signs and symptoms that may begin either in childhood or adult life. Neurological symptoms without signs of malabsorption have been observed for a long time in CD. In this report, an 8-year-old girl with CD presented with rarely seen dilated cardiomyopathy and stroke. The girl was admitted with left side weakness. Her medical history indicated abdominal distention, chronic diarrhea, failure to thrive, and geophagia. On physical examination, short stature, pale skin and a grade 2 of 6 systolic murmur were detected. Muscle strength was 0/5 on the left side, and 5/5 on the right side. Coagulation examinations were normal. Tests for collagen tissue diseases were negative. Factor V Leiden and prothrombin GA20210 mutations were negative. Tandem mass spectrophotometry and blood carnitine profiles were normal. Brain magnetic resonance imaging and cerebral angiography showed an infarction area at the basal ganglia level. Examinations of serologic markers and intestinal biopsy revealed CD. We emphasize that in differential diagnosis of ischemic stroke, CD should be kept in mind. PMID:20458770
Pruimboom, Leo; de Punder, Karin
Gluten-containing cereals are a main food staple present in the daily human diet, including wheat, barley, and rye. Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could "mask" its own toxicity by exorphins that are produced through gluten protein digestion.
Brancaglioni, Bianca de Cássia Alvarez; Rodrigues, Grasiele Caroline; Damião, Elaine Buchhorn Cintra; Queiroz, Márcia Silva; Nery, Márcia
Objective To understand the experience of children and adolescents living with type 1 diabetes and celiac disease. Method This is a qualitative exploratory-descriptive study. The participants were 3 children and 2 adolescents. The data were collected by means of semi-structured interviews between January and September 2012 at the participant's residence or at the diabetic outpatient clinic of the Hospital das Clinicas, Faculty of Medicine, University of Sao Paulo in São Paulo, Brazil. The content analysis technique was used to process the data. Results The key aspect of the illness experience of the patients was their diet, but with different meanings. The children had difficulty following the diet, while the adolescents reported that they had greater difficulty coping with the social and affective aspects of their diet. Conclusion The results reinforce the importance of nurses who seek strategies, together with the patients and their families, that help minimize the difficulties of these patients, especially with regard to managing the diet imposed by both diseases.
Jiang, Ling-ling; Zhang, Bing-ling; Liu, You-shi
Celiac disease (CD) is a type of intestinal malabsorption syndrome, in which the patients are intolerant to the gliadin in dietary gluten, resulting in chronic diarrhea and secondary malnutrition. The disease is common in Europe and the United States, but only sporadic reports are found in East Asia including China. Is CD really rare in China? We examined 62 patients by capsule endoscopy for chronic diarrhea from June 2003 to March 2008. Four patients with chronic diarrhea and weight loss were diagnosed to have CD. Under the capsule endoscopy, we observed that the villi of the proximal small bowel became short, and that the mucous membrane became atrophied in these four patients. Duodenal biopsies were performed during gastroscopy and the pathological changes of mucosa were confirmed to be Marsh 3 stage of CD. A gluten free diet significantly improved the conditions of the four patients. We suspect that in China, especially in the northern area where wheat is the main food, CD might not be uncommon, and its under-diagnosis could be caused by its clinical manifestations that could be easily covered by the symptoms from other clinical situations, particularly when it came to subclinical patients without obvious symptom or to patients with extraintestinal symptoms as the initial manifestations. PMID:19283870
Garner, C.P.; Murray, J.A.; Ding, Y.C.; Tien, Z.; van Heel, D.A.; Neuhausen, S.L.
Celiac disease is a common disease with a prevalence of ∼1%. A recent genome-wide association study (GWAS) and follow-up study identified eight loci significantly associated with celiac disease risk. We genotyped the top 1020 non-HLA single nucleotide polymorphisms (SNPs) from the GWAS study that were genotyped in the previous follow-up study. After quality control assessments, 975 SNPs were analyzed for association with 906 celiac disease cases and 3819 controls, using logistic regression. Additional genotype data were generated by imputation and analyzed across the regions showing the strongest statistical evidence for association. Twenty SNPs were associated with celiac disease with P < 0.01 in the current study as well as in the previous follow-up study, of which 16 had P < 0.001 and 11 had P < 1 × 10−11. Five of eight regions identified in the follow-up study were strongly associated with celiac disease, including regions on 1q31, 3q25, 3q28, 4q27 and 12q24. The strongest associations were at 4q27, the region most strongly associated in the GWAS and follow-up study and containing IL2 and IL21, and at 3q28 harboring LPP. In addition, we provide new evidence for an association, not previously reported, on 2q31 harboring a strong candidate gene, ITGA4. In conclusion, in this first follow-up study of celiac cases from the USA, we provide additional evidence that five of eight previously identified regions harbor risk alleles for celiac disease, and new evidence for an association on 2q31. The underlying functional mutations responsible for these replicated associations need to be identified. PMID:19648293
Capriati, T; Francavilla, R; Ferretti, F; Castellaneta, S; Ancinelli, M; Diamanti, A
We describe the nutritional status of a cohort of celiac disease (CD) children at presentation and during follow-up on gluten-free diet (GFD). Two Italian centers (Rome and Bari) prospectively enrolled 445 biopsy-confirmed CD children, diagnosed between 2009 and 2013. Body Mass Index was used as a measure of nutritional status according to Italian growth charts of Cacciari. The overweight/obese subject was 7.8% at onset and did not significantly increase during follow-up (9.8% at final assessment). The prevalence of overweight/obesity was significantly higher among males than females. Furthermore, overweight/obesity children as compared with those with normal weight were significantly older and had significantly lower levels of tTG antibodies. This study shows that some CD children are obese/overweight at diagnosis; therefore, overweight/obesity can be considered a rare but a possible mode of CD presentation. Thus, CD diagnosis must be considered even in overweight/obese children where this diagnosis can be easily missed.
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.
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
Krom, Hilde; Sprangers, Fleur; van den Berg, René; Benninga, Marc Alexander; Kindermann, Angelika
We present a 17-month-old girl with rapidly progressive unwillingness to sit, stand, play, and walk. Furthermore, she lacked appetite, vomited, lost weight, and had an iron deficiency. Physical examination revealed a cachectic, irritable girl with a distended abdomen, dystrophic legs with paraparesis, disturbed sensibility, and areflexia. An MRI scan revealed abnormal high signal intensity on T2-weighted images in the cord on the thoracic level, without cerebral abnormalities, indicating transverse myelitis (TM). Laboratory investigations revealed elevated immunoglobulin A antibodies against gliadin (1980.0 kU/L; normal, 0-10.1 kU/L) and tissue transglutaminase (110.0 kU/L; normal, 0-10.1 kU/L). Gastroscopy revealed villous atrophy in the duodenal biopsies and lymphocytic gastritis according to Marsh IIIb, compatible with celiac disease (CD). After the start of a gluten free diet and methylprednisolone, she recovered completely. To our knowledge, this is the first pediatric case of TM as manifestation of CD. We suggest that all children with TM or other neurologic manifestations of unknown origin should be screened for CD.
Leonard, Maureen M; Camhi, Stephanie; Huedo-Medina, Tania B; Fasano, Alessio
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.
Leonard, Maureen M.; Camhi, Stephanie; Huedo-Medina, Tania B.; Fasano, Alessio
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
Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran
Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636
Scanlon, Samantha A; Murray, Joseph A
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
Branchi, Federica; Locatelli, Martina; Tomba, Carolina; Conte, Dario; Ferretti, Francesca; Elli, Luca
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.
Sharma, Taral R; Kline, Daniel B; Shreeve, Daniel F; Hartman, David W
Celiac disease (CD) is a unique autoimmune disorder that occurs in genetically susceptible individuals after the ingestion of gluten, a protein found in wheat and some other cereals. The immunologically based inflammation induces atrophy of the villous structure of the jejunum, leading to malabsorption of variable severity. Subclinical and nonspecific forms of CD have been found to be increasingly common with a classic presentation of malabsorption syndrome (reference A). We present a case of OCD (obsessive compulsive disorder) in combination with depressive symptoms with the further complication of eating disorder not otherwise specified, in an adolescent male, for whom psychiatry was consulted because of treatment-refractory weight loss. We compare the elements of the case to other descriptions in the current, English language professional literature. Our literature review includes multiple search terms for the professional journals including, but not limited to, psychiatric comorbidities in celiac disease, behavioral disturbances of celiac disease, celiac disease in psychiatry, etc., to establish a possible association of psychiatric disorders, especially obsessive compulsive disorder and Celiac disease.
Masoodi, Mohsen; Mokhtare, Marjan; Agah, Shahram; Sina, Mohammad; Soltani-Kermanshahi, Mojtaba
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.
Gell, Gyöngyvér; Kovács, Krisztina; Veres, Gábor; Korponay-Szabó, Ilma R.; Juhász, Angéla
Brachypodium distachyon, a small annual grass with seed storage globulins as primary protein reserves was used in our study to analyse the toxic nature of non-prolamin seed storage proteins related to celiac disease. The main storage proteins of B. distachyon are the 7S globulin type proteins and the 11S, 12S seed storage globulins similar to oat and rice. Immunoblot analyses using serum samples from celiac disease patients were carried out followed by the identification of immune-responsive proteins using mass spectrometry. Serum samples from celiac patients on a gluten-free diet, from patients with Crohn’s disease and healthy subjects, were used as controls. The identified proteins with intense serum-IgA reactivity belong to the 7S and 11–12S seed globulin family. Structure prediction and epitope predictions analyses confirmed the presence of celiac disease-related linear B cell epitope homologs and the presence of peptide regions with strong HLA-DQ8 and DQ2 binding capabilities. These results highlight that both MHC-II presentation and B cell response may be developed not only to prolamins but also to seed storage globulins. This is the first study of the non-prolamin type seed storage proteins of Brachypodium from the aspect of the celiac disease. PMID:28051174
Cielo, Donatella; Morelli, Marinita; Gambino, Giuseppina; Zanzi, Delia; Strisciuglio, Caterina; Sperandeo, Maria Pia; Greco, Luigi; Auricchio, Renata
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
Szaflarska-Popławska, Anna; Chełchowska, Magdalena; Hozyasz, Kamil K.
Introduction Consumption of gluten proteins leads to an enteropathy characterised by lymphocytic infiltration of mucous membrane, crypts hypertrophy, and atrophy of villi. Enteropathy leads to disturbances in the immune system as well as secondary deficiency of vitamin E. Aim Analysis of the concentration of vitamin E in erythrocytes of patients with celiac disease. Material and methods Three experimental groups were distinguished among 77 patients with histologically confirmed celiac disease (mean age: 17 years): those who strictly respected gluten-free diet (group I, n = 48), patients breaking dietary recommendations (group II, n = 22), and those with newly diagnosed disease (group III, n = 7). Additionally, a control group consisting of healthy individuals with negative serological markers of celiac disease was formed (group IV, n = 20). Vitamin E concentration was determined by high performance liquid chromatography with ultraviolet detector. Results Significantly lower average concentration of vitamin E was demonstrated in erythrocytes in all examined groups of patients with celiac disease compared to the control group. Among the patients with celiac disease, the highest average concentration of vitamin E in erythrocytes was observed in the group who respected the gluten-free diet, a little lower in patients who violated dietary recommendations, and lowest among patients with newly diagnosed disease. These relationships, however, were not statistically significant. Conclusions Patients with celiac disease are at risk of vitamin E deficiency irrespective of their diet. Vitamin supplementation should be considered in their case, especially immediately after diagnosis of the disease and in case of breaking a gluten-free diet regime. PMID:28053684
Tagle, Martín; Nolte, Cecilia; Luna, Eduardo; Scavino, Yolanda
The case of a patient who was initially diagnosed with Systemic Lupus Erythematosus, with subsequent documentation of Celiac Disease histologically and serologically is reported. The patient presented elevation of the aminotransferases, upon detection of the Celiac Disease which was initially attributed to the underlying disease. However, despite the complete resolution of her articular symptoms with a gluten-free diet, the liver chemistry abnormalities persisted. This led to consider an autoimmune hepatitis as the cause which was documented with a liver biopsy three months after the diagnosis of the celiac disease and under a strict gluten-free diet. Treatment with prednisone and azathioprine was initiated with complete normalization of aminotransferase levels. We present the sequence of events with the results and a review of the literature.
Rodrigo, Luis; Hernández-Lahoz, Carlos; Lauret, Eugenia; Rodriguez-Peláez, Maria; Soucek, Miroslav; Ciccocioppo, Rachele; Kruzliak, Peter
Gluten ataxia (GA) has customarily been considered to be the main neurological manifestation of celiac disease (CD). In recent years, the condition of non-celiac gluten sensitivity (NCGS) has been defined, which includes some patients who are not considered "true celiacs." We performed a comparative clinicopathological study of these three entities. We studied 31 GA, 48 CD and 37 NCGS patients, prospectively in the same center for a period of 7 years. The protocol study included two serological determinations for gluten sensitivity [anti-gliadin IgA and IgG (AGA) and anti-tissue transglutaminase IgA (TG) antibodies], HLA-DQ2 typing, and duodenal histological assessment. Demographics and investigative findings were compared. Females were 55 % in GA, 75 % in CD (p < 0.001), and 47 % in NCGS (N.S.). GA patients were older (59 ± 14 years) than CD (43 ± 13 years) and NCGS (41 ± 8 years) groups (p < 0.001). AGA positivity was higher in GA (100 %) than in CD (48 %) groups (p < 0.001), but similar to NCGS patients (89 %; N.S.); TG positivity was lower in GA (3.2 %) than in CD (33.3 %; p < 0.001), but similar to NCGS (2.7 %; N.S.). DQ2 (+) was lower in GA (32.2 %) than in CD (89.6 %; p < 0.001), but similar to NCGS (29.7 %; N.S.). Lymphocytic enteritis (Marsh type 1) was lower in GA (9.6 %) than in CD (66.7 %; p < 0.001), but similar to NCGS (10.8 %; N.S.). The other gluten sensitivity-related characteristics measured were different to CD patients, but very close to NCGS. We conclude that GA patients are better classified within the NCGS group, than within CD.
Celiac disease is usually diagnosed by demonstrating gluten enteropathy in small bowel biopsy. Celiac specific antibodies are used as an initial screening test. The goal of this study is to test the relationship of the anti-tTG titer and severity of histological changes in Jordanian children with celiac disease. Method. The medical records of 81 children who had elevated anti-tTG titer and had duodenal biopsies available were retrospectively reviewed. Result. Assessing the association of anti-tTG titer with duodenal histopathological changes, 94% of those with high anti-tTG titer (≥180 U/mL) had histological evidence of celiac disease. There was statistically significant positive association between high anti-tTG titer and Marsh grading as 82% of patients with Marsh III had high anti-tTG titer (Chi2 18.5; P value 0.00; Odds Ratio 8.5). The fraction of patients with Marsh III who were correctly identified as positive by anti-tTG titer ≥ 180 U/mL was high (sensitivity = 81.6). Moreover, the fraction of patients with anti-tTG titer ≥ 180 U/mL who had Marsh III was also high (positive predictive value = 78.4). Conclusion. Anti-tTG titer ≥ 180 U/mL had significant positive association with Marsh III histopathological changes of celiac disease. PMID:27867394
Valitutti, Francesco; Trovato, Chiara Maria; Montuori, Monica; Cucchiara, Salvatore
The follow-up of celiac disease (CD) is challenging due to the scarcity of published data and the lack of standardized evidence-based protocols. The worldwide frequency and methods of CD follow-up appear to be heavily influenced by expert opinions of the individual physicians who assess children with CD. The aim of this review was to summarize the available studies on CD follow-up in children. We conducted a literature search with the use of PubMed, Medline, and Embase (from 1900 to 15 December 2016) for terms relevant to this review, including CD, follow-up, dietary adherence or dietary compliance, nutrition, comorbidities, complications, and quality of life. The aims of follow-up are as follows: to ensure strict adherence to a gluten-free diet, to ensure nutritional adequacy, to improve quality of life, and to prevent disease complications. For the correct evaluation of children with CD at follow-up, a clinical and biochemical evaluation is necessary on a regular basis. It is advisable to assess compliance, nutrition, comorbidities, or possible complications once a year at the referral center. Laboratory tests might be useful for a thorough evaluation of any patient with CD to rule out a micronutrient deficiency (full blood count, ferritin, folic acid, vitamin B-6, and vitamin B-12) and possible cardiovascular risk factors (glucose, LDL cholesterol, triglycerides). Biochemical evaluation is essential when there are clinical problems and should be customized on the basis of the specific clinical suspicion. Associated autoimmune thyroiditis should also be screened for yearly by measuring thyroid-stimulating hormone and thyroid autoantibody concentrations, regardless of symptoms, because hypothyroidism is often subtle and methods for early treatment are available and desirable. Although evidence-based recommendations for follow-up of pediatric patients with CD have not yet been established, we advise a yearly follow-up visit as the safest approach.
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
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
Fric, Premysl; Gabrovska, Dana; Nevoral, Jiri
Oats in a gluten-free diet increase the diet's nutritional value, but their use remains controversial. Contamination with prolamins of other cereals is frequent, and some clinical and experimental studies support the view that a subgroup of celiac patients may be intolerant to pure oats. Thus, this issue is more complex than previously suggested. In order to produce oats that are safe for all celiac patients, the following topics should be addressed: selection of oat cultivars with low avenin content, research on such recombinant varieties of oats, development of assay methods to detect avenins in oat products, guidelines for the agricultural processing of oats and the manufacture of oat products, as well as guidelines for following up with celiac patients who consume oats.
Wang, Da-Wei; Li, Da; Wang, Junjun; Zhao, Yue; Wang, Zhaojun; Yue, Guidong; Liu, Xin; Qin, Huanju; Zhang, Kunpu; Dong, Lingli; Wang, Daowen
Gliadins, specified by six compound chromosomal loci (Gli-A1/B1/D1 and Gli-A2/B2/D2) in hexaploid bread wheat, are the dominant carriers of celiac disease (CD) epitopes. Because of their complexity, genome-wide characterization of gliadins is a strong challenge. Here, we approached this challenge by combining transcriptomic, proteomic and bioinformatic investigations. Through third-generation RNA sequencing, full-length transcripts were identified for 52 gliadin genes in the bread wheat cultivar Xiaoyan 81. Of them, 42 were active and predicted to encode 25 α-, 11 γ-, one δ- and five ω-gliadins. Comparative proteomic analysis between Xiaoyan 81 and six newly-developed mutants each lacking one Gli locus indicated the accumulation of 38 gliadins in the mature grains. A novel group of α-gliadins (the CSTT group) was recognized to contain very few or no CD epitopes. The δ-gliadins identified here or previously did not carry CD epitopes. Finally, the mutant lacking Gli-D2 showed significant reductions in the most celiac-toxic α-gliadins and derivative CD epitopes. The insights and resources generated here should aid further studies on gliadin functions in CD and the breeding of healthier wheat.
Wang, Da-Wei; Li, Da; Wang, Junjun; Zhao, Yue; Wang, Zhaojun; Yue, Guidong; Liu, Xin; Qin, Huanju; Zhang, Kunpu; Dong, Lingli; Wang, Daowen
Gliadins, specified by six compound chromosomal loci (Gli-A1/B1/D1 and Gli-A2/B2/D2) in hexaploid bread wheat, are the dominant carriers of celiac disease (CD) epitopes. Because of their complexity, genome-wide characterization of gliadins is a strong challenge. Here, we approached this challenge by combining transcriptomic, proteomic and bioinformatic investigations. Through third-generation RNA sequencing, full-length transcripts were identified for 52 gliadin genes in the bread wheat cultivar Xiaoyan 81. Of them, 42 were active and predicted to encode 25 α-, 11 γ-, one δ- and five ω-gliadins. Comparative proteomic analysis between Xiaoyan 81 and six newly-developed mutants each lacking one Gli locus indicated the accumulation of 38 gliadins in the mature grains. A novel group of α-gliadins (the CSTT group) was recognized to contain very few or no CD epitopes. The δ-gliadins identified here or previously did not carry CD epitopes. Finally, the mutant lacking Gli-D2 showed significant reductions in the most celiac-toxic α-gliadins and derivative CD epitopes. The insights and resources generated here should aid further studies on gliadin functions in CD and the breeding of healthier wheat. PMID:28300172
Nacaroglu, Hikmet Tekin; Sandal, Ozlem Sarac; Bag, Ozlem; Erdem, Semiha Bahceci; Bekem Soylu, Ozlem; Diniz, Gulden; Ozturk, Aysel; Can, Demet
Introduction: Idiopathic Pulmonary Hemosiderosis (IPH) is a rare cause of alveolar hemorrhage, which is seen primarily in childhood. Celiac disease is defined as a chronic, immune-mediated enteropathy of the small intestine, caused by exposure to dietary gluten in genetically pre-disposed individuals. Association of IPH and celiac disease is known as Lane Hamilton syndrome. There are limited number of case reports of this syndrome in literature. Case Presentation: Although there were no growth and developmental delay and gastrointestinal symptoms like chronic diarrhea, chronic constipation, vomiting, abdominal bloating and pain in the two patients with IPH, they were diagnosed with Lane Hamilton Syndrome. After initiation of gluten-free diet, their IPH symptoms disappeared and hemoglobin levels were observed to return to normal. Conclusions: Even if there were no gastrointestinal symptoms in a patient with IPH, celiac disease should be investigated. These patients may benefit from gluten free diet and IPH symptoms may disappear. PMID:26495097
Ullery, Brant W; Pochettino, Alberto; Wang, Grace J; Jackson, Benjamin M; Fairman, Ronald M; Woo, Edward Y
Behçet's disease is a chronic, relapsing multisystemic inflammatory disorder characterized by recurrent orogenital aphthous ulcers, uveitis, and skin lesions. Vascular involvement occurs in up to 38% of these patients. Herein, we report a 19-year-old male who initially presented with an isolated celiac artery aneurysm that was treated with open surgical repair. The patient was subsequently diagnosed with Behçet's disease after the development of oral aphthous ulcers and multiple recurrent postoperative deep venous thromboses and thoracoabdominal arterial aneurysms. Ultimately, a hybrid approach was undertaken. This is the fifth celiac artery aneurysm ever reported in this patient group and the first to present with an isolated celiac artery aneurysm as the initial manifestation of Behçet's disease.
Biesiekierski, Jessica R; Muir, Jane G; Gibson, Peter R
The avoidance of wheat- and gluten-containing products is a worldwide phenomenon. While celiac disease is a well-established entity, the evidence base for gluten as a trigger of symptoms in patients without celiac disease (so-called 'non-celiac gluten sensitivity' or NCGS) is limited. The problems lie in the complexity of wheat and the ability of its carbohydrate as well as protein components to trigger gastrointestinal symptoms, the potentially false assumption that response to a gluten-free diet equates to an effect of gluten withdrawal, and diagnostic criteria for coeliac disease. Recent randomized controlled re-challenge trials have suggested that gluten may worsen gastrointestinal symptoms, but failed to confirm patients with self-perceived NCGS have specific gluten sensitivity. Furthermore, mechanisms by which gluten triggers symptoms have yet to be identified. This review discusses the most recent scientific evidence and our current understanding of NCGS.
Kaukinen, Katri; Collin, Pekka; Huhtala, Heini; Mäki, Markku
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.
Card, Tim; Ciclitira, Paul J; Swift, Gillian L; Nasr, Ikram; Sanders, David S; Ciacci, Carolina
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
Çekin, Ayhan Hilmi; Arslan, Şakir; Çağırcı, Göksel; Küçükseymen, Selçuk; Çay, Serkan; Harmandar, Ferda Akbay; Yeşil, Bayram
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
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.)...
Chiarioni, G; Bassotti, G; Germani, U; Battaglia, E; Brentegani, M T; Morelli, A; Vantini, I
The mechanisms responsible for bowel disturbances in celiac disease are still relatively unknown. Recent reports suggested that small bowel motor abnormalities may be involved in this pathological condition; however, there are no studies addressing small bowel transit in celiac disease before and after a gluten-free diet. We studied the mouth-to-cecum transit time of a caloric liquid meal in a homogeneous group of celiac patients presenting with clinical and biochemical evidence of malabsorption and complaining of diarrhea. Sixteen patients were recruited and investigated by means of hydrogen breath test through ingestion of 20 g lactulose together with an enteral gluten-free diet formula. A urinary D-xylose test was also done in each patient. Both breath tests and D-xylose tests were carried out basally and after a period of gluten-free diet. Twenty healthy volunteers were recruited as a control group and underwent the same breath testing. At the time of the diagnosis, mouth-to-cecum transit time was significantly prolonged in celiacs with respect to controls (243 +/- 10 vs 117 +/- 6 min, P = 0.0001). The D-xylose test was also abnormal (average urinary concentration 2.8 +/- 0.25 g, normal values >4.5). No correlation was found in patients between mouth-to-cecum transit time and urinary D-xylose output (r = 0.22). After the gluten-free diet period, mouth-to-cecum transit time in celiacs was significantly reduced compared to prediet transit (134 +/- 8 vs 243 +/- 10 min, P = 0.0001) and did not show statistical difference when compared to that found in controls (P = 0.1). The D-xylose test reverted to normal in all but two subjects, who were found to be noncompliant with the diet. Mouth-to-cecum transit time is significantly prolonged in patients affected by untreated celiac disease when compared to healthy controls. This alteration might not be correlated to intestinal malabsorption, and the prolonged orocecal transit could be due to impaired small bowel function
Moroz, S P; Hadorn, B; Rossi, T M; Haworth, J C
We report on a 40-yr-old man with both primary enteropeptidase deficiency and celiac disease. He suffered from severe intestinal malabsorption and growth failure as a child. Enteropeptidase deficiency was found and pancreatic enzyme replacement therapy resulted in a growth spurt. Enteropeptidase levels in his intestinal mucosa and intraluminal fluid remained very low throughout childhood and early adult life. Celiac disease was confirmed by characteristic abnormalities in tests of intestinal function and in mucosal biopsies, which recovered when he instituted a gluten-free diet. He remains clinically intolerant to gluten as an adult. Enteropeptidase levels have remained abnormally low whether or not his intestinal mucosa has been normal in response to gluten restriction. Enteropeptidase levels have previously been shown to be normal in untreated celiac patients. The relationship between the two disorders remains unclear.
Papadatou, B; Ferretti, F; Colistro, F; Castellucci, G; Lucidi, V; Ricci, S; Cerminara, R; Bella, S; Colombo, A M; Gambarara, M
IgA antigliadin antibodies (IgA-AGA) have been determined with an enzyme immunoassay in 2.141 pediatric patients. High levels of IgA were found in 98% of 53 celiac patients (1st biopsy), in 81% of 16 celiac patients after gluten challenge, while high levels of these antibodies were not found in 200 patients on gluten-free diet. Moreover high levels of IgA-AGA were found in 29% of 48 patients with normal jejunal biopsy and in 4% of 1.824 patients with gastrointestinal problems other than celiac disease. Our results confirm the data report in literature about the sensibility and the specificity of the IgA-AGA dosage as a screening test for celiac disease, but the possibility of false pathological and false normal values confirms the intestinal biopsy, as the main procedure for the diagnosis of celiac disease.
Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto
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
Pietzak, Michelle Maria
Celiac disease is the only autoimmune condition for which we know the environmental trigger: gluten. Complete removal of gluten from the diet in a patient with celiac disease should result in symptomatic, serologic, and histologic remission. However, compliance with the gluten-free diet, especially in the United States, is extremely challenging. Compliance can be measured both noninvasively, by dietary history and measurement of serum antibodies, and invasively, by using endoscopic and histologic criteria. The advantages and disadvantages of these various modalities are discussed. The highest rates of compliance are reported in patients who are diagnosed as young children, whereas adolescents and those diagnosed via mass serologic screening have the most transgressions. Barriers to compliance include the poor palatability of gluten-free foods, confusing food-labeling practices, and common comorbid psychologic burdens such as anxiety and depression. Because celiac disease is a multisystemic disorder, physicians need to be aware of the potential autoimmune, nutritional, and malignant complications. An algorithm for the follow-up and management of the newly diagnosed celiac disease patient is presented, which includes regular follow-up; measurement of serum antibodies; eliciting a detailed dietary history; and examination for signs and symptoms of nutritional deficiencies, malignancy, and other autoimmune diseases. Ideally, a team approach to the follow-up of the newly diagnosed patient should include regular supervision by an interested physician, medical nutritional counseling by a registered dietician, and access to local and national support groups knowledgeable about this condition.
Rodríguez-Sánchez, Joaquín; Martín-Dávila, Francisco; López-Viedma, Bartolomé; Galván-Fernández, M D; Alonso-Lablanca, María; Olmedo-Camacho, José; García-Rojo, Marcial; Rodríguez-Sánchez, Eduardo
Among the many complications of celiac disease, mesenteric lymph node syndrome cavitated is considered one of the rarest, there is few case series published in the literature. The etiology and pathophysiology are unknown but because of its high mortality rate, estimated to be around 50%, it should recognize at an early stage in order to institute appropriate therapy as soon as possible.
Niederhofer, Helmut; Pittschieler, Klaus
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…
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...
Weizman, Z; Hamilton, J R; Kopelman, H R; Cleghorn, G; Durie, P R
A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac disease. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immuno-reactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.
Cataldo, Francesco; Montalto, Giuseppe
In the past, celiac disease was believed to be a chronic enteropathy, almost exclusively affecting people of European origin. The availability of new, simple, very sensitive and specific serological tests (anti-gliadin, anti-endomysium and anti-transglutaminase antibody assays) have shown that celiac disease is common not only in Europe and in people of European ancestry but also in the developing countries where the major staple diet is wheat (Southern Asia, the Middle East, North West and East Africa, South America), both in the general population and in the groups at risk. Gluten intolerance thus appears to be a widespread public health problem and an increased level of awareness and clinical suspicion are needed in the New World where physicians must learn to recognize the variable clinical presentations (classical, atypical and silent forms) of celiac disease. In the developing countries, both serological screening in the general population and serological testing in groups at risk are necessary for an early identification of celiac patients. The gluten-free diet poses a challenging public health problem in the developing countries, especially since commercial gluten-free products are not available. PMID:17465493
Ameratunga, Rohan; Barker, Russell William; Steele, Richard Henderson; Deo, Maneka; Woon, See-Tarn; Yeong, Mee Ling; Koopmans, Wikke
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.
Munera-Picazo, Sandra; Ramírez-Gandolfo, Amanda; Burló, Francisco; Carbonell-Barrachina, Angel Antonio
Celiac disease is an autoimmune disease that affects the villi of the small intestine causing abdominal pain, gas, diarrhea, or bad absorption due to gluten intolerance. The only treatment for this disease consists of a lifelong gluten free diet; this is, celiac people cannot consume products containing gluten, such as wheat, barley, and rye, but they can use rice and corn. Thus, rice flour is mainly used for the manufacturing of the basic products of this population. Unfortunately, rice can contain high contents of total (t-As) and inorganic (i-As) arsenic. The current study demonstrated that products for celiac children with a high percentage of rice contained high concentrations of arsenic (256 and 128 μg kg⁻¹). The daily intake of i-As ranged from 0.61 to 0.78 μg kg⁻¹ body weight (bw) in children up to 5 y of age; these values were below the maximum value established by the EFSA Panel (8.0 μg kg⁻¹ bw per day), but it should be considered typical of populations with a high exposure to this pollutant. Finally, legislation is needed to improve the labeling of these special rice-based foods for celiac children; label should include information about percentage, geographical origin, and cultivar of the used rice.
Bodé, S; Weile, B; Krasilnikoff, P A; Gudmand-Høyer, E
Serum gliadin antibodies (IgA/IgG) were determined in 191 consecutive children (median age, 2.75 years; range, 0.33-15.5 years) admitted for a small-intestinal biopsy on suspicion of celiac disease. The test was a diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). Of these 191, 14 (7.3%) appeared to have untreated celiac disease. Depending on the choice of cut-off value of the test (combined determination of IgA and IgG), the sensitivity was 86-100%, the specificity was 97-99%, and the positive/negative predictive values were 70-92% and 99-100%, respectively. No variation according to age was found. Gliadin antibodies were determined in 47 children who had well-treated celiac disease. Fourteen of these children were also investigated when challenged with gluten. Gliadin antibodies (IgA or IgG) decreased significantly in 13 of 13 cases when the patients shifted from a gluten-containing diet to a gluten-free one. During the gluten challenge, the IgG and IgA increased in 14 of 14 and 11 of 14 cases, respectively (two patients suffered from IgA deficiency). In eight patients who later appeared to be free of celiac disease, the gliadin antibodies were determined on gluten-free diet and during gluten challenge; no significant differences in gliadin antibodies were found. We conclude that this test is useful in selecting patients with symptoms suggesting celiac disease for a small-intestinal biopsy. The test seems to be of some value in monitoring the effects of a gluten-free diet and during gluten challenge.
Meyts, Isabelle; Jansen, Katrien; Renard, Marleen; Bossuyt, Xavier; Roelens, Filip; Régal, Luc; Lagae, Lieven; Buyse, Gunnar
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.
Kergaravat, Silvina V; Beltramino, Luis; Garnero, Nidia; Trotta, Liliana; Wagener, Marta; Isabel Pividori, Maria; Hernandez, Silvia R
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%.
van Beurden, Yvette H; van Gils, Tom; van Gils, Nienke A; Kassam, Zain; Mulder, Chris J J; Aparicio-Pagés, Nieves
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.
López Cruz, M C; Martín Mateos, M A; Giner Muñoz, M T; Plaza Martín, A M; Sierra Martínez, J I
Common variable immunodeficiency is a disorder characterised by hypogammaglobulinemia with B-lymphocytes in peripheral blood and repeated infections. We report a child with a diagnosis of diabetes mellitus and celiac disease during lactation, and in whom common variable immunodeficiency was diagnosed at the age of 5. During evolution of the disease he presented multiple respiratory infections in spite of substitution therapy with gamma globulins. He presented pulmonary fibrosis with a pulmonary volume reduced, and a spirometric restrictive patron. Immunologically, he presents reduction in CD4 lymphoid population. He expresses the alleles DQ2 A1 0501 and B1 which are strongly associated with susceptibility to insulin-dependent diabetes mellitus and celiac disease, but don't express antigens HLA class II DR3 and DR4 that are more frequent in these entities. The main disease and all the complications had affected his curve pondostatural.
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
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
Passera, Andrea Helena; Passera, Mario Luis; Higa, Antonio Luis; Nuñez, Maria; Armando, Lucas; Barzón, Silvia
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.
Brown, Amy C
Gluten sensitivity appears to be emerging as a separate condition from celiac disease, yet no clear definition or diagnosis exists. As a result, patients with gluten sensitivity experience delayed diagnosis and continuing symptoms if they consume gluten. This emerging medical problem may involve human genetics, plant genetic modifications, gluten as a food additive, environmental toxins, hormonal influences, intestinal infections and autoimmune diseases. The treatment is similar to that for celiac disease - a gluten-free diet. The use of a gluten-free diet or an elimination diet is encouraged in assisting people to determine whether or not they are gluten sensitive. It is time to not only recognize, but to treat and further research gluten sensitivity, as unconfirmed environmental factors continue to spread this problem further into the general population.
Egberg, Matthew; Nelson, Catherine; Eickoff, Jens
Background: A gap exists in the literature on celiac disease populations and the response to hepatitis B vaccination. Objective: To identify pediatric patients with celiac disease who received the primary hepatitis B vaccination and investigate their response to vaccine. Design/Methods: Patients underwent blood draw for hepatitis B surface antibody titers. Patients with undetectable or non-protective HBsAb titers were contacted. Study outcome measures and patient characteristics variables were summarized by means, standard deviations, medians, and ranges. A two-sample t-test was used to compare normally distributed continuous variables between responders and non-responders. Results: In all, 58% of patients did not meet the threshold for “protective” antibody titers. The mean time between completion of hepatitis B vaccination and diagnosis of celiac disease was 8.1 years for responders versus 10.5 years for non-responders. In a multivariate analysis, time between completion of vaccine and diagnosis of celiac disease was statistically significant predictor of response with an adjusted odds ratio of 0.69 (95% confidence interval: 0.50–0.95; p = 0.021). Conclusion: Our celiac disease population shows a high hepatitis B vaccine failure. The time between completion of vaccine series and diagnosis of celiac disease is an independent predictor for response. PMID:26770758
Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.
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.
Emilsson, Louise; Murray, Joseph A.; Leffler, Daniel A.; Ludvigsson, Jonas F.
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
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.
Giménez, María J; Real, Ana; García-Molina, M Dolores; Sousa, Carolina; Barro, Francisco
Some studies have suggested that the immunogenicity of oats depends on the cultivar. RP-HPLC has been proposed as a useful technique to select varieties of oats with reduced immunogenicity. The aim of this study was to identify both the avenin protein patterns associated with low gluten content and the available variability for the development of new non-toxic oat cultivars. The peaks of alcohol-soluble avenins of a collection of landraces and cultivars of oats have been characterized based on the RP-HPLC elution times. The immunotoxicity of oat varieties for patients with celiac disease (CD) has been tested using a competitive ELISA based on G12 monoclonal antibody. The oat lines show, on average, seven avenin peaks giving profiles with certain similarities. Based on this similarity, most of the accessions have been grouped into avenin patterns. The variability of RP-HPLC profiles of the collection is great, but not sufficient to uniquely identify the different varieties of the set. Overall, the immunogenicity of the collection is less than 20 ppm. However, there is a different distribution of toxicity ranges between the different peak patterns. We conclude that the RP-HPLC technique is useful to establish groups of varieties differing in degree of toxicity for CD patients.
Giménez, María J.; Real, Ana; García-Molina, M. Dolores; Sousa, Carolina; Barro, Francisco
Some studies have suggested that the immunogenicity of oats depends on the cultivar. RP-HPLC has been proposed as a useful technique to select varieties of oats with reduced immunogenicity. The aim of this study was to identify both the avenin protein patterns associated with low gluten content and the available variability for the development of new non-toxic oat cultivars. The peaks of alcohol-soluble avenins of a collection of landraces and cultivars of oats have been characterized based on the RP-HPLC elution times. The immunotoxicity of oat varieties for patients with celiac disease (CD) has been tested using a competitive ELISA based on G12 monoclonal antibody. The oat lines show, on average, seven avenin peaks giving profiles with certain similarities. Based on this similarity, most of the accessions have been grouped into avenin patterns. The variability of RP-HPLC profiles of the collection is great, but not sufficient to uniquely identify the different varieties of the set. Overall, the immunogenicity of the collection is less than 20 ppm. However, there is a different distribution of toxicity ranges between the different peak patterns. We conclude that the RP-HPLC technique is useful to establish groups of varieties differing in degree of toxicity for CD patients. PMID:28209962
Tye-Din, Jason A; Stewart, Jessica A; Dromey, James A; Beissbarth, Tim; van Heel, David A; Tatham, Arthur; Henderson, Kate; Mannering, Stuart I; Gianfrani, Carmen; Jewell, Derek P; Hill, Adrian V S; McCluskey, James; Rossjohn, Jamie; Anderson, Robert P
Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible.
Selek, Ozgur; Memisoglu, Kaya; Selek, Alev
Bilateral non traumatic femoral neck fatigue fracture is a rare condition usually occurring secondary to medical conditions such as pregnancy, pelvic irradiation, corticosteroid exposure, chronic renal failure and osteomalacia. In this report, we present three young female patients with bilateral femoral neck fracture secondary to osteomalacia. The underlying cause of osteomalacia was Celiac disease in all patients. The patients were treated with closed reduction and internal fixation with cannulated lag screws. They were free of pain and full weight bearing was achieved at three months. There were no complications, avascular necrosis and nonunion during the follow up period. In patients with bone pain, non traumatic fractures and muscle weakness, osteomalacia should be kept in mind and proper diagnostic work-up should be performed to identify the underlying cause of osteomalacia such as celiac disease.
Serena, Gloria; Camhi, Stephanie; Sturgeon, Craig; Yan, Shu; Fasano, Alessio
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.
Ambrosetto, G; Antonini, L; Tassinari, C A
We report the electroclinical ictal findings of four epileptic patients with clinically asymptomatic celiac disease (CD). Celiac disease diagnosis was suspected by past history and/or computed tomography (CT) findings in all patients and confirmed by laboratory tests and jejunal biopsy. All patients had paroxysmal visual manifestations and ictal EEG discharges arising from the occipital lobe. Epilepsy evolution was favorable in two patients and severe in 2, regardless of CT evidence of occipital corticosubcortical calcifications in 2 patients. Occipital lobe seizures may be characteristic of the epilepsy related to CD, and epileptic patients with these seizures of unknown etiology should be carefully investigated for malabsorption. If past history and/or laboratory tests suggest gastrointestinal (GI) dysfunction they should also undergo small intestinal biopsy even if they do not have GI tract symptoms.
Gasbarrini, Giovanni; Miele, Luca; Corazza, Gino R; Gasbarrini, Antonio
A case of a young woman died in Italy during the first century AD is presented. She had short height (140 cm), clinical history of anemia, and a decreased bone mass with evidence of osteoporosis and bone fragility. The archeologic artifacts from the tomb and with the quality of burial architecture suggest that the tomb was built for a rich person in an area with extensive culture of wheat. The wellness of the area is supported by the lack of other bodies found with signs of malnutrition. Clinical presentation and the possible continuous exposure to wheat seem to suggest a case of celiac disease. This case could be the first case of this condition since that one described by Areteus of Cappadocia in 250 BC and could be helpful to clarify the phylogenetic tree of celiac disease.
Parfenov, A I; Bykova, S V; Sabel'nikova, E A; Maev, I V; Baranov, A A; Bakulin, I G; Krums, L M; Bel'mer, S V; Borovik, T E; Zakharova, I N; Dmitrieva, Yu A; Roslavtseva, E A; Kornienko, E A; Khavkin, A I; Potapov, A S; Revnova, M O; Mukhina, Yu G; Shcherbakov, P L; Fedorov, E D; Belousova, E A; Khalif, I L; Khomeriki, S G; Rotin, D L; Vorob'eva, N G; Pivnik, A V; Gudkova, R B; Chernin, V V; Vokhmyanina, N V; Pukhlikova, T V; Degtyarev, D A; Damulin, I V; Mkrtumyan, A M; Dzhulai, G S; Tetruashvili, N K; Baranovsky, A Yu; Nazarenko, L I; Kharitonov, A G; Loranskaya, I D; Saifutdinov, R G; Livzan, M A; Abramov, D A; Osipenko, M F; Oreshko, L V; Tkachenko, E I; Sitkin, S I; Efremov, L I
The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.
Bizzaro, N; Tozzoli, R; Villalta, D; Fabris, M; Tonutti, E
Celiac disease (CD) is a gluten-dependent immune-mediated disease with a prevalence in the general population estimated between 0.3% and 1.2%. Large-scale epidemiological studies have shown that only 10-20% of cases of CD are identified on the basis of clinical findings and that laboratory tests are crucial to identify subjects with subtle or atypical symptoms. The correct choice and clinical use of these diagnostic tools may enable accurate diagnosis and early recognition of silent CD cases. In this review, we have considered some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase-gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD.
Vereckei, Edit; Mester, Adám; Hodinka, László; Temesvári, Péter; Kiss, Emese; Poór, Gyula
There have been only scattered reports suggesting that musculoskeletal manifestations including back pain and sacroiliac joint involvement may be associated with celiac disease. In order to confirm this issue in a larger cohort, rheumatic manifestations were analyzed in 21 adult celiac patients using a comprehensive clinical, laboratory and radiological analysis. The diagnosis of celiac disease was based on the histopathology of jejunal biopsy specimens. The mean duration of celiac disease was 15 (0-31) years. All patients were currently on gluten-free diet and none of the patients had gastrointestinal symptoms at the time of the study. Using various imaging techniques, involvement of the sacroiliac joints was confirmed in 70% of celiac patients. Imaging revealed different morphological changes in the sacroiliac joint, e.g. accumulation of synovial fluid, synovitis, erosion with concomitant sclerosis, sacroiliitis or calcification of the ligament. These changes probably represent different clinical stages and/or manifestations of the same process. In a follow-up study of eight patients, after 11 years on a gluten-free diet, the great majority of patients had no clinical symptoms; yet, a subclinical progression of the sacroiliac joint involvement could be verified. Our results suggest the importance of regular rheumatologic follow-up of patients with celiac disease.
Lionetti, Elena; Catassi, Carlo
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.
Amaya-González, Sonia; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Lobo-Castañón, M Jesús
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.
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
Giammaria, G; Ciavarelli Macozzi, L; Giammaria, A F
Oral cavity alterations are often indicative sign of chronic gastrointestinal disorders, such as malabsorption and malnutrition syndromes. The relationship between oral pathology and intestinal diseases is rarely a chance association. This prompted odontostomatological research to focus on the study of alterations of the oral cavity, hypotetical markers of intestinal disorders if they can be measured in terms of frequency and incidence, as a tool for the early diagnosis of the intestinal disease itself. This paper should be seen against this background since it examines the possible connection between celiac disease and the presence of oral alterations as an index of disease.
Usai-Satta, Paolo; Oppia, Francesco; Scarpa, Mariella; Giannetti, Cristiana; Cabras, Francesco
Objective Delayed gastric emptying has been frequently detected in patients with untreated celiac disease. According to several studies, gluten withdrawal showed to be effective in normalizing the gastric emptying rate. The aim of this study was to evaluate the gastric emptying rate of solids in patients with celiac disease before and after a gluten-free diet. Methods Twelve adult patients with celiac disease (age range 20-57 years) and 30 healthy controls (age range 30-54 years) underwent a (13)C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After at least 12 months of a gluten-free diet, celiac patients underwent a new (13)C-octanoic acid breath test. A symptom score was utilized to detect dyspeptic and malabsorption symptoms in all the patients. Results The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. On a gluten-free diet, surprisingly, the gastric emptying did not normalize despite an improvement of symptom score. No significant correlation between abnormal gastric emptying and specific symptom patterns, anthropometric parameters or severity of histological damage was found. Conclusions This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing gut hormone function. The persistence of these abnormalities on a gluten free diet suggests the presence of a persistent low-grade mucosal inflammation with a permanent perturbation of the neuro-immunomodulatory regulation.
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
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
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
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.
Caio, Giacomo; Giorgio, Roberto De; Venturi, Alessandro; Giancola, Fiorella; Latorre, Rocco; Boschetti, Elisa; Serra, Mauro; Ruggeri, Eugenio; Volta, Umberto
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
Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H
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.
Almeida, Lucas Malta; Gandolfi, Lenora; Pratesi, Riccardo; Uenishi, Rosa Harumi; de Almeida, Fernanda Coutinho; Selleski, Nicole
Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when p < 0.05. Disease risk was expressed as 1 : N for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.2 (β2/β2 or β2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.2 (β2/β2) showed high CD risk of 1 : 10 (p < 0.0001). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5. PMID:28042478
Card, Timothy R; Kaukinen, Katri; Bai, Julio; Zingone, Fabiana; Sanders, David S; Murray, Joseph A
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
Magliocca, F M; Bonamico, M; Petrozza, V; Mariani, P; Correr, S; Familiari, G; Carpino, F
The structure and ultrastructure of the villi of small intestinal mucosa was examined in 237 duodenal or jejunal biopsies taken from children with active celiac disease and during gluten-free diet. All biopsies were processed for light and scanning electron microscopy. Conventional histology showed four different morphological aspects: total and subtotal villous atrophy in patients on unrestricted diet, partial villous atrophy and normal mucosa during gluten-free diet. Scanning electron microscopy demonstrated that in active celiac disease the severity of the intestinal lesions was related to individual vulnerability to gluten. Our results showed that during dietary treatment the process of mucosal healing was constant and strictly time-dependent. Furthermore, the ultrastructural examination has been relevant in evaluating the evolution of the villous regeneration. In this study a classification regarding the healing process of the small intestinal mucosa correlated with the time of start of dietary therapy is proposed.
Marín Viegas, Vanesa S; Acevedo, Gonzalo R; Bayardo, Mariela P; Chirdo, Fernando G; Petruccelli, Silvana
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
Marín Viegas, Vanesa S.; Acevedo, Gonzalo R.; Bayardo, Mariela P.; Chirdo, Fernando G.; Petruccelli, Silvana
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
van Wanrooij, R L J; Bouma, G; Bontkes, H J; Neefjes-Borst, A; van Grieken, N C; von Blomberg, B M E; Mulder, C J J
Objectives: Refractory celiac disease (RCD) is a severe cause of non-responsive celiac disease (CD) due to its association with the enteropathy associated T-cell lymphoma (EATL). Conflicting data exist on the prevalence and the clinical manifestations of RCD type I (RCD I) and type II (RCD II). The aim of the current study was to provide insight in the incidence of RCD and in the distinction with other causes of non-responsive CD. Methods: A total of 106 CD patients were referred to our tertiary referral center between January 2006 and December 2011 for evaluation of non-responsive CD. In addition, a questionnaire was sent to all 82 gastroenterology departments in the Netherlands to reveal whether a patient with RCD was currently being evaluated or had been treated between 2006 and 2012. Results: During a 6 year period, a total of 31 patients were diagnosed with RCD (19 RCD I and 12 RCD II). The nationwide survey revealed 5 additional patients with RCD I and one patient with RCD II. This leads to an annual incidence of RCD of 0.83/10.000 CD patients. The remaining patients were diagnosed with involuntary gluten ingestion (21.7%), delayed mucosal recovery (11.3%), enteropathy associated T-cell lymphoma (7.5%) and autoimmune enteropathy (1.8%). Conclusions: This nationwide study reveals a low incidence of RCD in the Netherlands. Nevertheless, RCD is a clinically relevant disease entity in CD patients non-responsive to the gluten-free diet. PMID:28125074
Badyal, Rama Kumari; Sachdeva, Man Updesh Singh; Varma, Neelam; Thapa, Babu Ram
An association between severe aplastic anemia and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus, and thyroid disorders. Herein we report a patient with celiac disease who was not strictly following a gluten-free diet and presented with progressive pallor, fever, and weakness of 1 month's duration. On investigation, he had pancytopenia, which on subsequent evaluation revealed aplastic anemia. An association between aplastic anemia and celiac disease has rarely been reported. To the best of author's knowledge, only 1 pediatric case of celiac disease associated with aplastic anemia has been published. This is the second report to suggest such an association in children.
Coton, T; Grassin, F; Maslin, J; Gidenne, S; Sarret, D; Petitjeans, F; Benois, A; Kraemer, P; Cloatre, G
Celiac disease is poorly documented in intertropical Africa. The purpose of this retrospective report was to describe 8 cases observed at the Groupement Medico-Chirurgical of Bouffard Hospital in Djibouti (Horn of Africa) between January 2003 and January 2006. There were 5 females and 3 males ranging in age from 9 months to 17 years old (mean age: 48 months). Six patients were of Somali ethnic origin and two of Yemenite ethnic origin. Six were classified as middle class and 2 as lower class. All forms were symptomatic associating constant loss of weight with digestive manifestations (diarrhoea and vomiting). Diagnosis of celiac disease was based on the presence of anti-gliadin antibodies IgA and IgG associated with anti-endomysium or anti-transglutaminase antibodies that were measured in six and two cases respectively. Gastroduodenal endoscopy performed in three cases including two with duodenal biopsy demonstrated villous atrophy associated with gross of intra-epithelial lymphocytosis. A gluten-free diet initiated in five patients led to clinical improvement in four cases with a follow-up of 8.25 months. The findings of this study in Djibouti show that celiac disease exists in intertropical Africa. Its presentation is quite similar to elsewhere but diagnosis is more difficult due to poor knowledge about the disease and limited diagnostic facilities. Favourable response to presumptive treatment by a gluten-free diet is an alternative for diagnosis especially in Djibouti where eating habits differ from those in industrialized countries and this type of diet is easier to follow.
Chen, Xi; Hnida, Kathrin; Graewert, Melissa Ann; Andersen, Jan Terje; Iversen, Rasmus; Tuukkanen, Anne; Svergun, Dmitri; Sollid, Ludvig M.
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
Nordyke, Katrina; Olsson, Cecilia; Hernell, Olle; Ivarsson, Anneli
Breast milk is the initial natural food for infants, but already during the second half year complementary feeding is essential. Epidemiological research, first on celiac disease and later on atopic diseases, has driven a paradigm shift with respect to most favorable age to introduce complementary feeding. Simplified, this implies a shift from later to earlier introduction, which is now taken into account in recommendations on infant feeding. Complementary feeding, including all foods, should not be initiated for any infant before 4 months of age, and not later than around 6 months, including infants with elevated disease risk (e.g. for celiac disease or atopic diseases). Motivating reasons could be that ongoing breastfeeding provides an 'immunological umbrella' and/ or a different age interval gives a 'window of opportunity' for developing oral tolerance towards gluten and other food antigens. This will for some infants be in conflict with recent WHO recommendations on exclusive breastfeeding for 6 months. Epidemiology has evolved over time and could, if increasingly used, contribute even more to innovations in pediatric nutrition and other phenomena related to population health.
Ribeiro, Miguel; Rodriguez-Quijano, Marta; Nunes, Fernando M; Carrillo, Jose Maria; Branlard, Gérard; Igrejas, Gilberto
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.
Diamanti, Antonella; Capriati, Teresa; Bizzarri, Carla; Ferretti, Francesca; Ancinelli, Monica; Romano, Francesca; Perilli, Alessia; Laureti, Francesca; Locatelli, Mattia
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.
Sams, Aaron; Hawks, John
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.
Caproni, Marzia; Bonciolini, Veronica; D'Errico, Antonietta; Antiga, Emiliano; Fabbri, Paolo
Cutaneous manifestations of intestinal diseases are increasingly reported both in the adult and in the children, and this association cannot longer be considered a simple random. Besides the well-known association between celiac disease (CD) and dermatitis herpetiformis (DH), considered as the cutaneous manifestation of gluten-dependent enteropathy, is more frequently reported also the association with other mucocutaneous diseases. Among these there are both autoimmune, allergic, and inflammatory diseases, but also a more heterogeneous group called miscellaneous. The knowledge about pathogenic, epidemiological, clinical, and diagnostic aspects of CD is increasing in recent years as well as those about DH, but some aspects still remain to be defined, in particular the possible pathogenetic mechanisms involved in the association between both CD and DH and CD and other immunological skin diseases. The aim of this paper is to describe the skin diseases frequently associated with CD, distinguishing them from those which have a relationship probably just coincidental. PMID:22693492
Rios, Lorena P.; Khan, Aliya; Sultan, Muhammad; McAssey, Karen; Fouda, Mona A.; Armstrong, David
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
Moeller, Sina; Canetta, Pietro A.; Taylor, Annette K.; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H.; Kiryluk, Krzysztof; Alaedini, Armin
IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy. PMID:24732864
Ramos Plá, M; Julve Pardo, R; Primo Vera, J; Fernández Chinchilla, J; Gómez Belda, A B; García Ferrer, L
A high percentage of diagnosed cases of coeliac disease are oligosymptompatic. Various atypical manifestations such as hypertransaminasemia may guide diagnosis when the disease is suspected. We present two cases of coeliac disease, which were diagnosed on the basis of hypertransaminasemia of unknown origin. One of the patients lacked the gastrointestinal symptoms suggestive of disease. We also retrospectively review (January 1990-December 1998) all the cases of coeliac disease diagnosed in our center in order to establish the frequency of liver enzyme alterations in patients with coeliac disease and their evolution on a gluten-free diet. The importance of sprue suspicion in guiding diagnosis in patients with cryptogenic hypertransaminasemia is highlighted as is the need to rule out underlying liver disease in coeliac patients with persistent hypertransaminasemia after withdrawing gluten from the diet.
Hoff, Clarissa Jb
It depends on the antibody levels in the blood work. Symptomatic patients with serologic levels of immunoglobulin A anti-tissue transglutaminase (IgA anti-tTG) or immunoglobulin G anti-deamidated gliadin peptide antibody (IgG anti-DGP) greater than 10 times the upper limits of normal--especially if they also are positive for endomysial antibodies (EMA) and human leukocyte antigen DQ2 (HLA-DQ2 or HLA-DQ8)--may not need an intestinal biopsy to confirm the diagnosis of celiac disease.
Pané, A; Orois, A; Careaga, M; Saco, A; Ortega, E; Vidal, J; Leyes, P; Amor, A J
To our knowledge, this is the first reported case of clinical onset of celiac disease (CD) following duodenal switch surgery. A 61-year-old obese woman developed severe diarrhea soon after bariatric surgery (BS), which was unresponsive to standard medical treatment. After the most common diarrhea etiologies in the immediate postoperative period have been excluded, serological tests were performed. Final diagnosis was determined by anti-tissue transglutaminase antibody positivity. In light of this case report, we propose that CD should be ruled out in any patient presenting with typical or atypical symptoms after BS, regardless of the latency of onset.
Sjöberg, Veronika; Hollén, Elisabet; Pietz, Grzegorz; Magnusson, Karl-Eric; Fälth-Magnusson, Karin; Sundström, Mia; Holmgren Peterson, Kajsa; Sandström, Olof; Hernell, Olle; Hammarström, Sten; Högberg, Lotta; Hammarström, Marie-Louise
OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa. METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR. RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04). CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients. PMID:24964993
Ress, Krista; Luts, Katrin; Rägo, Tiina; Pisarev, Heti; Uibo, Oivi
The aims of the study were to analyze the trends and characteristics of the incidence and clinical presentation of childhood celiac disease (CD) from 1976 to 2010 in Estonia. The study included all children up to 19 years of age diagnosed with small bowel biopsy proven CD. During a 35-year period, CD was diagnosed in 152 children in Estonia (68 boys, median age 2.3 years). From 1976 to 1980, the age-standardized incidence rate of CD was 0.10 per 100,000 person-years. After the introduction of gliadin and endomysium antibody screening (in conjunction with activities directed to increase the physicians awareness), the incidence rate increased from 0.48 in 1986-1990 to 1.55 per 100,000 person-years in 1991-1995. After initiating screening with anti-tissue transglutaminase antibodies in 2003 and routine screening for CD among all children with newly diagnosed type 1 diabetes in 2005, the incidence rate increased from 1.59 in 2001-2005 to 3.14 per 100,000 person-years in 2006-2010 (median age 6.8 years). Our nationwide study demonstrates a more than 30-fold increase in the incidence of childhood CD over a 35-year period in Estonia, along with changing patterns in the presentation of pediatric CD. In addition to the impact of use of novel CD screening methods, active search and rising of the awareness among doctors may have strongest effect. Both environmental and social factors could be also involved in the increase in CD incidence.
Sreedharanunni, Sreejesh; Varma, Neelam; Sachdeva, Man Updesh Singh; Gupta, Kirti; Pai, Rekha; Kochhar, Rakesh; Malhotra, Pankaj; Varma, Subhash
Indolent γδ T cell lymphomas/leukemias are rare and overlap with the morphological spectrum of large granular lymphocyte (LGL) leukemia. We report an extremely rare case of CD103(+) γδ T LGL leukemia in a patient with celiac disease who presented with refractory diarrhea. Whether the refractory diarrhea in our patient was a manifestation of LGL leukemia itself or whether the clonal LGL expansion is a manifestation of refractory celiac disease (RCD) remains an enigma. This report highlights the diagnostic difficulties and the need of consensus in categorizing clonal CD103(+) lymphocytosis in patients with RCD.
Dieli-Crimi, Romina; Núñez, Concepción; Estrada, Lourdes; López-Palacios, Natalia
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.
Boccuti, Viera; Perrone, Antonio; D'Introno, Alessia; Campobasso, Anna; Sangineto, Moris; Sabbà, Carlo
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.
van den Broeck, Hetty; Hongbing, Chen; Lacaze, Xavier; Dusautoir, Jean-Claude; Gilissen, Ludovicus; Smulders, Marinus; van der Meer, Ingrid
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.
Munera-Picazo, Sandra; Burló, Francisco; Carbonell-Barrachina, Ángel Antonio
Celiac disease (CD) may affect up to 1% of the Western population. It is a disease whose diagnosis has been made mainly in childhood, but now the profile has changed, with one out of five newly diagnosed individuals being over 65 years old. The only treatment for this population is a gluten-free diet. Therefore, the objective of this study was to analyse the occurrence of arsenic (As) in gluten-free products, basically those rice-based, intended for celiac adult consumers. The current study demonstrated that these rice-based products contained important contents of total arsenic (t-As) (up to 120 μg kg(-1)) and inorganic arsenic (i-As) (up to 85.8 μg kg(-1)). It was estimated that the contents of t-As and i-As in rice used as the main ingredient of these foods were as high as 235 and 198 μg kg(-1), respectively. The estimated daily intake of i-As was 0.46 and 0.45 μg kg(-1) bw in women and men of 58 and 75 kg of body weight (bw), respectively. These values indicate that a health risk to these consumers cannot be excluded. Finally, legislation is needed to delimit the safety intake by health agencies and to improve the labelling of these special rice-based foods for celiac adult consumers. The label should include information about percentage, geographical origin and cultivar of the rice used; besides and if companies want to clearly prove the safety of their products, the exact content of i-As should also be included.
Krifa, F; Knani, L; Sakly, W; Ghedira, I; Essoussi, A S; Boukadida, J; Ben Hadj Hamida, F
A 9-year old girl with a history of diabetes mellitus type 1, presented with visual loss of the left eye. The right eye examination was unremarkable. Slit-lamp examination revealed few small and fine keratic precipitates. We noted 2+ flare in the vitreous. There was no choroiditis, papillitis or retinal vasculitis. No aetiology was found. The patient was treated by topical and systemic corticosteroids without any improvement. Celiac disease was discovered by the presence of celiac antibodies in the work-up of joint pain and diabetes mellitus type 1. Antiendomysium antibodies and anti-transglutaminase antibodies were both positive. A small bowel biopsy confirmed celiac disease. A gluten free diet was set up and corticosteroids were tapered off. Recovery of the uveitis was obvious during gluten free diet and normalized within two months.
Nassef, Hossam M; Bermudo Redondo, M Carmen; Ciclitira, Paul J; Ellis, H Julia; Fragoso, Alex; O'Sullivan, Clara K
Celiac disease is a gluten-sensitive enteropathy that affects as much as 1% of the population. Patients with celiac disease should maintain a lifelong gluten-free diet, in order to avoid serious complications and consequences. It is essential to have methods of analysis to reliably control the contents of gluten-free foods, and there is a definitive need for an assay that is easy to use, and can be used on site, to facilitate the rapid testing of incoming raw materials or monitoring for gluten contamination, by industries generating gluten-free foods. Here, we report on the development of an electrochemical immunosensor exploiting an antibody raised against the putative immunodominant celiac disease epitope, for the measurement of gliadin content and potential celiac toxicity of a foodstuff. To develop the gliadin immunosensor, we explored the use of two surface chemistries, based on the use of dithiols, 22-(3,5-bis((6-mercaptohexyl)oxy)phenyl)-3,6,9,12,15,18,21-heptaoxadocosanoic acid (1) and 1,2-dithiolane-3-pentanoic acid (thioctic acid) (2), for anchoring of the capture antibody. The different surface chemistries were evaluated in terms of time required for formation of self-assembled monolayers, stability, susceptibility to nonspecific binding, reproducibility, and sensitivity. The thioctic acid self-assembled monolayer took more than 100 h to attain a stable surface and rapidly destabilized following functionalization with capture antibody, while the heptaoxadocosanoic acid surface rapidlyformed (less than 3 h) and was stable for at least 5 days, stored at room temperature, following antibody immobilization. Both surface chemistries gave rise to highly sensitive immunosensors, with detection limits of 5.5 and 11.6 ng/mL being obtained for 1 and 2, respectively, with nonspecific binding of just 2.7% of the specific signal attained. The immunosensors were extremely reproducible, with RSD of 5.2 and 6.75% obtained for 1 and 2 (n = 5, 30 ng/mL), respectively
Sóñora, Cecilia; Arbildi, Paula; Rodríguez-Camejo, Claudio; Beovide, Verónica; Marco, Alicia; Hernández, Ana
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.
Wei, Guoxian; Tian, Na; Siezen, Roland; Schuppan, Detlef; Helmerhorst, Eva J
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.
Hozyasz, Kamil; Czerwińska, Barbara
Coeliac disease is characterized by life-long gluten intolerance. There are a wide variety of clinical presentations, which range from severe diarrhoea and weight loss to asymptomatic forms. The primary treatment for coeliac disease is the removal of gluten from the diet to prevent both immediate and long-term complications. The case of 16-year-old girl with coeliac disease was presented. At the age of 2 years the patient with impaired growth and abnormal stools was suspected to have coeliac disease. She experienced symptomatic improvement on gluten-free diet, but after 3 years the treatment was discontinued. The patient denied gastrointestinal or skin problems. At the age of 14 years Raynaud's phenomenon was observed for the first time. Two years later episodes of Raynaud's phenomenon involved all fingers and toes. Body mass index (BMI) was 23.8 kg/m2. Levels of free-carnitine, tocopherol, vitamin B12 were below normal limits and homocysteine level was increased. Antiendomysial IgA, antireticulin IgA, antigliadin IgA and IgG antibodies were positive. The duodenal mucosa showed total villous atrophy. Gluten free-diet and multivitamin supplementation provided some benefit in reducing Raynaud's phenomenon. The patient's well being has improved markedly. Atypical coeliac disease is usually seen in adolescents and adults in whom features of overt malabsorption are often absent. In cases of health problems occurring in persons with history of malabsorption syndrome in childhood suspicion of coeliac disease should be heightened and appropriate evaluation undertaken.
Parra-Medina, Rafael; Molano-Gonzalez, Nicolás; Rojas-Villarraga, Adriana; Agmon-Levin, Nancy; Arango, Maria-Teresa; Shoenfeld, Yehuda; Anaya, Juan-Manuel
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
GARUD, S.; LEFFLER, D.; DENNIS, M.; EDWARDS-GEORGE, J.; SARYAN, D.; SHETH, S.; SCHUPPAN, D.; JAMMA, S.; KELLY, C. P.
Summary Background Previous studies yielded conflicting results regarding the presence of an association between celiac disease (CD) and psychiatric disorders including depression. This association has not been studied in the United States. Aim To determine the prevalence of psychiatric and autoimmune disorders in patients with CD in the US compared to control groups. Methods In a case control study, the prevalence of psychiatric and autoimmune disorders was compared in 600 CD patients, 200 irritable bowel syndrome (IBS) patients and 200 healthy controls. Results The prevalence of depression in CD was 17.2% and was similar to that in IBS (18.5%, P = 0.74) and controls (16.0%, P = 0.79). Among CD patients, type I DM was identified as a significant risk factor for depression (P < 0.01) with 37% of patients with both CD and type I DM having clinical depression. Conclusion The prevalence of depression in CD is similar to that in other chronic gastrointestinal diseases and healthy controls. However, there is a markedly elevated risk of depression in patients with both type I DM and CD. Differing rates of type 1 DM among celiac populations may account for disparity in published rates of depression in patients with CD. PMID:19183153
Black, Katherine Elizabeth; Skidmore, Paula; Brown, Rachel Clare
Food intolerance is becoming increasingly prevalent, and increasing numbers of athletes have celiac disease. This poses challenges as dietary recommendations for exercise are largely based on gluten-containing carbohydrate-rich foods. The K4 cycle race covers 384 km around the Coromandel Peninsula, New Zealand. Lack of sleep, darkness, and temperature variations pose a number of nutritional challenges. Limited food choices present those with celiac disease with even greater challenges. This case study describes the intakes of one such athlete during training and competing in the K4. Nutritional intakes were obtained during training using weighed-food records and during the race via dietary recall and the weighing of foods pre- and post-race. As simple substitution of gluten-containing foods for gluten-free foods leads to increased energy intake, alternatives need to be considered. During the race, insufficient energy was consumed to meet the nutritional guidelines for endurance performance. This was probably due to the nature of the course, racing conditions, the consistency of gluten-free food, and, toward the end of the race, sensory-specific satiety.
Magazzú, G; Bottaro, G; Cataldo, F; Iacono, G; Di Donato, F; Patane, R; Cavataio, F; Maltese, I; Romano, C; Arco, A
By screening the patient list of four Sicilian centers of gastroenterology and those with gluten-free product consumption, 1074 patients (607 females and 467 males) with celiac disease, diagnosed between 1975 and 1989, were identified. A maximum cumulative incidence rate by birth cohort was reached in 1986 (1.65/1000). When the incidence rate was adjusted for the years of follow-up, the actual standardized rate was 3 cases per 1000 live births. Growth failure and chronic diarrhea were the most common symptoms, but a diminishing trend for chronic diarrhea was observed when symptoms were distributed by year of diagnosis. Even though 61.1% of all cases were diagnosed within six months from the onset of symptoms, mean age at diagnosis showed an increasing trend, from less than two years to approximately four years of age. The results of our study showed an increasing incidence of celiac disease due to diagnosis of less typical cases at an older age and also to a steady increase in the rate of diagnosis of cases with a classic clinical picture.
Mangiagli, A; Campisi, S
The spectrum of clinical manifestations of coeliac disease, the most common chronic intestinal disorder in children, has widened considerably over the past years and new associations with other diseases, both immunological and non-immunological, have been described. AGA and EMA have proved to be an efficient screening method both in populations with gastrointestinal pathologies and in groups of pauci- or even asymptomatic subjects. The clinical picture of beta-thalassemia has gradually altered over the years owing to improved treatment. However, growth is still affected in a considerable proportion of thalassemic patients. A number of hormonal and other causes, combined in varying ways, contribute to determining this clinical condition. The authors report a case of coeliac disease in an adolescent with thalassemia major characterised by anorexia, arrest of weight gain and low stature. The identification of a new association between coeliac disease and thalassemia major highlights the need to search for this pathology in all thalassemic patients who present scarce growth in stature and weight.
Rajani, Seema; Alzaben, Abeer; Shirton, Leanne; Persad, Rabindranath; Huynh, Hien Q; Mager, Diana R; Turner, Justine M
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
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
Nair, Ramesan Girish; Kaur, Gurwinder; Kochhar, Rakesh; Dhawan, Devinder Kumar
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
Datta Mitra, Ananya; Gupta, Asha; Jialal, Ishwarlal
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.
Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.
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
Ortiz-Sánchez, Juan P; Cabrera-Chávez, Francisco; de la Barca, Ana M Calderón
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.
El Mouzan, Mohammad I.; Saeed, Elshazaly; Alanazi, Aziz; Alghamdi, Sharifa; Anil, Shirin; Assiri, Asaad
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
Silano, Marco; Agostoni, Carlo; Guandalini, Stefano
Celiac disease (CD) is a permanent auto-immune enteropathy, triggered in genetically predisposed individuals by the ingestion of dietary gluten. Gluten is the alcohol-soluble protein component of the cereals wheat, rye and barley. CD is a multifactorial condition, originating from the interplay of genetic and environmental factors. The necessary environmental trigger is gluten, while the genetic predisposition has been identified in the major histocompatibility complex region on chromosome 6p21, with over 90% of CD patients expressing HLA DQ2 and the remaining celiac patients express DQ8. The fact that only about 4% of DQ2/8-positive individuals exposed to gluten develop CD, has led to the recognition that other genetic and environmental factors are also necessary. In the last few years, several epidemiological studies have suggested that the timing of the introduction of gluten, as well as the pattern of breastfeeding, may play an important role in the subsequent development of CD. Here, we present and review the most recent evidences regarding the effect of timing of gluten introduction during weaning, the amount of gluten introduced and simultaneous breastfeeding, on the development of CD.
Dowd, A Justine; Jung, Mary E
Strict adherence to a gluten-free diet (GFD) is the only treatment for preventing both short- and long-term consequences of celiac disease. Given that following a strict GFD can be difficult, evidence-based strategies are needed to improve the psychological experience of living with celiac disease and following the GFD. Self-compassion appears to be an important component of effectively self-regulating one's behavior to cope with a chronic disease. The main goal of this study was to examine the relationships between self-compassion and management of celiac disease as assessed by (a) adherence to a strict GFD and (b) celiac-specific quality of life (CQoL). The secondary goal of this study was to explore self-regulatory efficacy (i.e., confidence in one's ability to self-manage behavior to follow a strict GFD) and concurrent self-regulatory efficacy (i.e., one's confidence to self-manage other valued life goals while following a strict GFD) as mediators of the relationship between self-compassion and the primary outcomes (adherence and CQoL). In this prospective study, 200 North American adults diagnosed with celiac disease completed online questionnaires at two time points (baseline and 1 month later). Self-compassion at baseline directly predicted stricter adherence (at Time 2; b = -0.63, p = 0.006) and enhanced CQoL (at Time 2; b = -0.50, p = 0.001). Further, self-compassion (at Time 1) also indirectly predicted stricter Time 2 adherence through self-regulatory efficacy (at Time 1; b = -0.26, 95% CI [-0.58, -0.04], R(2) = 0.29) and enhanced Time 2 CQoL through concurrent self-regulatory efficacy (at Time 1; b = -0.07, 95% CI [-0.14, -0.03], R(2) = 0.33). This was the first study to assess the effects of self-compassion in relation to the psychological experience of coping with celiac disease and following a GFD. The findings indicate that self-compassion, self-regulatory efficacy and concurrent self-regulatory efficacy are important cognitions in
Pantaleoni, Stefano; Luchino, Massimo; Adriani, Alessandro; Pellicano, Rinaldo; Stradella, Davide; Ribaldone, Davide Giuseppe; Sapone, Nicoletta; Isaia, Gian Carlo; Di Stefano, Marco; Astegiano, Marco
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.
Zevit, Noam; Shamir, Raanan
The diagnostic criteria for celiac disease (CD) have undergone significant change during the past several decades following a better understanding of the pathogenesis of the disease and the identification of sensitive and specific serum markers. In 2012, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published new diagnostic algorithms, which for the first time questioned the need for histological evaluation in all patients, and identified specific requirements for omitting intestinal biopsies from diagnosis requirements. Here, we briefly review the evolution of the diagnostic algorithms, emerging data which may be integrated into the diagnosis algorithm in the future and suggest key points which should be considered while we continue to develop and refine the diagnostic criteria for CD in an age of personalized medicine.
Khaleghi, Shahryar; Ju, Josephine M; Lamba, Abhinav; Murray, Joseph A
Celiac disease (CD) is a common chronic immune disease triggered by gluten. Gliadin peptides pass through the epithelial layers, either paracellularly or transcellularly, to launch a potent adaptive immune response in the lamina propria. This aberrant immune response leads to diverse gastrointestinal and extra-gastrointestinal symptoms. Currently, the only treatment for CD is a strict lifelong adherence to a gluten-free diet (GFD), which can be challenging. An early effect of gluten in CD is an increase in gut permeability. Larazotide acetate, also known as AT-1001, is a synthetic peptide developed as a permeability regulator primarily targeting CD. In vitro studies indicate that larazotide acetate is capable of inhibiting the actin rearrangement caused by gliadin and clinical studies have been conducted using this peptide as a therapy for CD.
El-Salhy, Magdy; Hatlebakk, Jan Gunnar; Gilja, Odd Helge; Hausken, Trygve
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.
Pouchot, Jacques; Despujol, Carole; Malamut, Georgia; Ecosse, Emmanuel; Coste, Joël; Cellier, Christophe
Background and Objective Celiac disease (CD) is a common chronic autoimmune disorder. Both the manifestations of the disease and the burden of the compulsory life-long gluten-free diet (GFD) have been shown to be associated with impairment of health-related quality of life. The objectives of this study were to provide a cross-cultural adaptation of the specific quality of life “Celiac Disease Questionnaire” (CDQ) and to analyze its psychometric properties. Materials and Methods A cross-cultural French adaptation of the CDQ (F-CDQ) was obtained according to the revised international guidelines. The questionnaire was administered at baseline to 211 patients with biopsy proven CD followed-up in a single tertiary referral centre. The questionnaire was also administered after 7 days and 6 months. Reliability (intraclass correlation coefficients (ICC), Cronbach's alpha and Bland and Altman graphical analysis), validity (factorial structure and Rasch analysis, convergent validity), and responsiveness (effect size) of the F-CDQ were studied. Results The reliability of the F-CDQ was excellent with ICC and Cronbach's alpha coefficients being between 0.79 and 0.94 for the four subscales and the total score. The factorial structure and the Rasch analysis showed that the four dimensions of the original instrument were retained. Correlations with external measures (a generic measure of quality of life, an anxiety and depression instrument, a self-assessed disease severity, and clinical manifestations) were all in the expected direction confirming the validity of the instrument. Responsiveness was studied and effect sizes ≥0.20 were demonstrated for most of the subscales for patients who reported improvement or deterioration after 6 months. Conclusion The F-CDQ retains the psychometric properties of the original instrument and should be useful in cross-national surveys and to assess outcome in clinical trials involving patients with CD. PMID:24788794
Zucchini, Laure; Giusti, Delphine; Gatouillat, Grégory; Servettaz, Amélie; Tabary, Thierry; Barbe, Coralie; Pham, Bach-Nga
Algorithms for celiac disease diagnosis provided by guidelines are based primarily on anti-tissue transglutaminase 2 (TG2) antibodies and/or anti-endomysium antibodies. The place of anti-deamidated gliadin peptide (DGP) antibodies is less well established. This study was designed to assess the clinical relevance of anti-DGP antibodies. Two thousand and twenty-six consecutive unselected patients systematically tested for anti-TG2, endomysium, gliadin, DGP antibodies and IgA dosage were investigated. The serological interpretation was assessed by analyzing the medical records of patients. From the 1984 newly investigated patients suspected of celiac disease, 10% had at least one celiac marker. Anti-TG2, anti-endomysium, anti-gliadin and anti-DGP antibodies were found in 1.1%, 0.6%, 6.8% and 4.1% of cases respectively, with different combinations. The diagnosis of celiac disease was retained in 0.45% of patients. When using the duodenal biopsies as a gold standard, analysis of the anti-DGP diagnosis performance showed that the specificity and the predictive positive value (PPV) were lower than that of the anti-TG2 assay. The combined detection of anti-TG2 and anti-DGP antibodies had a lower PPV than that of anti-TG2 and anti-endomysium antibodies (p = 0.04). When analyzing the contribution of anti-DGP antibodies as an additional marker to both anti-TG2 and anti-endomysium antibodies, the PPV of the three associated antibodies was shown to be significantly lower than the PPV of the both anti-TG2 and anti-endomysium antibodies (p = 0.04). As a conclusion, anti-DGP antibodies may not have the diagnosis value required as an additional screening test to anti-TG2 antibodies for identifying celiac disease patients in medical centers where anti-endomysium detection is available.
Abraham, Gad; Kikianty, Eder; Wang, Qiao; Rawlinson, Dave; Shi, Fan; Haviv, Izhak; Stern, Linda
Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets. PMID:28282431
Laurikka, Pilvi; Salmi, Teea; Collin, Pekka; Huhtala, Heini; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle
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
Goudey, Benjamin; Abraham, Gad; Kikianty, Eder; Wang, Qiao; Rawlinson, Dave; Shi, Fan; Haviv, Izhak; Stern, Linda; Kowalczyk, Adam; Inouye, Michael
Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets.
... is a protein found in wheat, rye, and barley — grains that are in many everyday foods. Most ... free" one because wheat-free products may have barley and rye (gluten-containing grains) in them. previous ...
... be able to figure out which dishes at restaurants or friends' homes contain gluten. Some restaurants in your town might offer gluten-free dishes ... local support group may have a list of restaurants where the chef is familiar with the gluten- ...
... usually made from barley) marinades matzo modified food starch (most food manufacturers will now specify the source ... modified cornstarch , which is OK, or modified wheat starch, which is not) nondairy creamer pastas salad dressings ...
... Villi are usually described as microscopic, finger-like projections. Weird, huh? Fingers in your intestines! But don' ... out and will usually order a screening blood test. If the screening tests show a person might ...
De Nitto, Daniela; Monteleone, Ivan; Franzè, Eleonora; Pallone, Francesco; Monteleone, Giovanni
Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.
Mones, R L
Great progress has been made in the field of celiac disease (CD). During the past 50 years we have come to understand a great deal about the pathogenesis, clinical spectrum, and treatment. Great advances have been made in the technology of diagnosing CD. Heretofore, the gold standard used for diagnosis of CD is the small intestinal biopsy. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition has recently issued guidelines that state that some patients do not require a biopsy for diagnosis. This review traces the history of CD with a particular attention to the evolution of the technology involved in the field. The question of the need for biopsy or not is discussed.
Jacobs, Lauren; Gilliam, Amy; Khavari, Nasim; Bass, Dorsey
The prevalence of celiac disease (CD) is increasing and may be as high as 1% of the US population. The typical presentation of CD generally includes gastrointestinal symptoms, but more individuals are presenting with extraintestinal manifestations. A wide variety of dermatologic associations have been described with CD, including alopecia, dermatitis herpetiformis, and enamel hypoplasia. In this report we describe three girls with CD who presented with hypopigmented skin lesions and pruritus in the perivaginal and perianal areas, consistent with the diagnosis of lichen sclerosus (LS). All three presented within 1 year to the same practitioner. To our knowledge, this association has not previously been explored in the literature. These cases elucidate a possible relationship between CD and LS.
Hoffmanová, Iva; Sánchez, Daniel
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.
Stepniak, Dariusz; Spaenij-Dekking, Liesbeth; Mitea, Cristina; Moester, Martine; de Ru, Arnoud; Baak-Pablo, Renee; van Veelen, Peter; Edens, Luppo; Koning, Frits
Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4-5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.
Freeman, Hugh J
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.
Freeman, Hugh J.
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
Pisapia, Laura; Camarca, Alessandra; Picascia, Stefania; Bassi, Virginia; Barba, Pasquale; Del Pozzo, Giovanna; Gianfrani, Carmen
HLA genes represent the main risk factor in autoimmune disorders. In celiac disease (CD), the great majority of patients carry the HLA DQA1*05 and DQB1*02 alleles, both of which encode the DQ2.5 molecule. The formation of complexes between DQ2.5 and gluten peptides on antigen-presenting cells (APCs) is necessary to activate pathogenic CD4(+) T lymphocytes. It is widely accepted that the DQ2.5 genes establish the different intensities of anti-gluten immunity, depending whether they are in a homozygous or a heterozygous configuration. Here, we demonstrated that HLA DQA1*05 and DQB1*02 gene expression is much higher than expression of non-CD-associated genes. This influences the protein levels and causes a comparable cell surface exposure of DQ2.5 heterodimers between DQ2.5 homozygous and heterozygous celiac patients. As a consequence, the magnitude of the anti-gluten CD4(+) T cell response is strictly dependent on the antigen dose and not on the DQ2.5 gene configuration of APCs. Furthermore, our findings support the concept that the expression of DQ2.5 genes is an important risk factor in celiac disease. The preferential expression of DQ2.5 alleles provides a new functional explanation of why these genes are so frequently associated with celiac disease and with other autoimmune disorders.
de Jong, Hein C.; Salentijn, Elma M. J.; Dekking, Liesbeth; Bosch, Dirk; Hamer, Rob J.; Gilissen, Ludovicus J. W. J.; van der Meer, Ingrid M.; Smulders, Marinus J. M.
Gluten proteins from wheat can induce celiac disease (CD) in genetically susceptible individuals. Specific gluten peptides can be presented by antigen presenting cells to gluten-sensitive T-cell lymphocytes leading to CD. During the last decades, a significant increase has been observed in the prevalence of CD. This may partly be attributed to an increase in awareness and to improved diagnostic techniques, but increased wheat and gluten consumption is also considered a major cause. To analyze whether wheat breeding contributed to the increase of the prevalence of CD, we have compared the genetic diversity of gluten proteins for the presence of two CD epitopes (Glia-α9 and Glia-α20) in 36 modern European wheat varieties and in 50 landraces representing the wheat varieties grown up to around a century ago. Glia-α9 is a major (immunodominant) epitope that is recognized by the majority of CD patients. The minor Glia-α20 was included as a technical reference. Overall, the presence of the Glia-α9 epitope was higher in the modern varieties, whereas the presence of the Glia-α20 epitope was lower, as compared to the landraces. This suggests that modern wheat breeding practices may have led to an increased exposure to CD epitopes. On the other hand, some modern varieties and landraces have been identified that have relatively low contents of both epitopes. Such selected lines may serve as a start to breed wheat for the introduction of ‘low CD toxic’ as a new breeding trait. Large-scale culture and consumption of such varieties would considerably aid in decreasing the prevalence of CD. PMID:20664999
Allegretti, Yessica L.; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W.; Chirdo, Fernando G.
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
Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda
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.
Garcia-Quintanilla, Albert; Miranzo-Navarro, Domingo
We propose a biochemical mechanism for celiac disease and non-celiac gluten sensitivity that may rationalize many of the extradigestive disorders not explained by the current immunogenetic model. Our hypothesis is based on the homology between the 33-mer gliadin peptide and a component of the NMDA glutamate receptor ion channel - the human GRINA protein - using BLASTP software. Based on this homology the 33-mer may act as a natural antagonist interfering with the normal interactions of GRINA and its partners. The theory is supported by numerous independent data from the literature, and provides a mechanistic link with otherwise unrelated disorders, such as cleft lip and palate, thyroid dysfunction, restless legs syndrome, depression, ataxia, hearing loss, fibromyalgia, dermatitis herpetiformis, schizophrenia, toxoplasmosis, anemia, osteopenia, Fabry disease, Barret's adenocarcinoma, neuroblastoma, urinary incontinence, recurrent miscarriage, cardiac anomalies, reduced risk of breast cancer, stiff person syndrome, etc. The hypothesis also anticipates better animal models, and has the potential to open new avenues of research.
Dieli-Crimi, Romina; Cénit, M Carmen; Núñez, Concepción
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.
Moccia, Marcello; Pellecchia, Maria Teresa; Erro, Roberto; Zingone, Fabiana; Marelli, Sara; Barone, Damiano Giuseppe; Ciacci, Carolina; Strambi, Luigi Ferini; Barone, Paolo
Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption-related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age- and sex-matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 +/- 6.5). In the CD population, no significant correlation was found between RLS and either gluten-free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end-stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD.
Spatola, Bradley N; Murray, Joseph A; Kagnoff, Martin; Kaukinen, Katri; Daugherty, Patrick S
A general strategy to identify serum antibody specificities associated with a given disease state and peptide reagents for their detection was developed using bacterial display peptide libraries and multiparameter flow cytometry (MPFC). Using sera from patients with celiac disease (CD) (n = 45) or healthy subjects (n = 40), bacterial display libraries were screened for peptides that react specifically with antibodies from CD patients and not with those from healthy patients. The libraries were screened for peptides that simultaneously cross-react with CD patient antibodies present in two separate patient groups labeled with spectrally distinct fluorophores but do not react with unlabeled non-CD antibodies, thus affording a quantitative separation. A panel of six unique peptide sequences yielded 85% sensitivity and 91% specificity (AUC = 0.91) on a set of 60 samples not used for discovery, using leave-one-out cross-validation. Individual peptides were dissimilar with known CD-specific antigens tissue transglutaminase (tTG) and deamidated gliadin, and the classifier accuracy was independent of anti-tTG antibody titer. These results demonstrate that bacterial display/MPFC provides a highly effective tool for the unbiased discovery of disease-associated antibody specificities and peptide reagents for their detection that may have broad utility for diagnostic development.
de Souza, M Cristina P; Deschênes, Marie-Eve; Laurencelle, Suzanne; Godet, Patrick; Roy, Claude C; Djilali-Saiah, Idriss
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.
Celiac disease has been associated with several neurologic disorders which may result from micronutrient deficiencies, coexisting autoimmune conditions, or gluten sensitivity. Copper deficiency can produce multiple neurologic manifestations. Myeloneuropathy is the most common neurologic syndrome and it is often irreversible, despite copper replacement. We report the case of a 55-year-old man who presented with progressive proximal limb weakness and weight loss in the setting of untreated celiac disease without gastrointestinal symptoms. He had anemia, neutropenia, and severe hypocupremia. The pattern of weakness raised the suspicion that there was an underlying myopathy, although this was not confirmed by electrodiagnostic studies. Weakness and hematologic abnormalities resolved completely within 1 month of total parenteral nutrition with copper supplementation and a gluten-free diet. Myopathy can rarely occur in patients with celiac disease, but the mechanism is unclear. Pure proximal limb weakness has not been previously reported in copper deficiency. We propose that this may represent a novel manifestation of hypocupremia and recommend considering copper deficiency and gluten sensitivity in patients presenting with proximal limb weakness. PMID:27994896
Avila, J David; Lacomis, David
Celiac disease has been associated with several neurologic disorders which may result from micronutrient deficiencies, coexisting autoimmune conditions, or gluten sensitivity. Copper deficiency can produce multiple neurologic manifestations. Myeloneuropathy is the most common neurologic syndrome and it is often irreversible, despite copper replacement. We report the case of a 55-year-old man who presented with progressive proximal limb weakness and weight loss in the setting of untreated celiac disease without gastrointestinal symptoms. He had anemia, neutropenia, and severe hypocupremia. The pattern of weakness raised the suspicion that there was an underlying myopathy, although this was not confirmed by electrodiagnostic studies. Weakness and hematologic abnormalities resolved completely within 1 month of total parenteral nutrition with copper supplementation and a gluten-free diet. Myopathy can rarely occur in patients with celiac disease, but the mechanism is unclear. Pure proximal limb weakness has not been previously reported in copper deficiency. We propose that this may represent a novel manifestation of hypocupremia and recommend considering copper deficiency and gluten sensitivity in patients presenting with proximal limb weakness.
Erdes, Svetlana I.; Antishin, Anton S.
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of dietary gluten from some cereals mainly in individuals carrying the HLA-DQ2 and/or HLA-DQ8 haplotypes. As an autoimmune disease, CD is manifested in the small intestine in the form of a progressive and reversible inflammatory lesion due to immune response to self-antigens. Indeed, CD is one of the most challenging medicosocial problems in current gastroenterology. At present, the global CD prevalence is estimated at approximately 1% based on data sent from different locations and available CD screening strategies used. However, it is impossible to estimate global CD prevalence without all the data from the world, including Russia. In this review, we summarize the data on the incidence and prevalence of CD across geographically distinct regions of Russia, which are mostly present in local Russian scientific sources. Our conclusion is that the situation of CD prevalence in Russia is higher than is commonly believed and follows global tendencies that correspond to the epidemiologic situation in Europe, America, and Southwest Asia. PMID:28316996
Jericho, Hilary; Assiri, Asaad; Guandalini, Stefano
Since the first description of celiac disease (CeD) by Samuel Gee in 1888 and the later "miraculous discovery" that bread was responsible for this condition following World War II in Europe, there has been an exponential growth of knowledge regarding CeD. Just when we thought that we knew everything there was to know about it, the disease is, however, offering new challenges, with its presentation having significantly morphed over the years from cases of overt gastrointestinal symptoms, malnutrition, and atrophic villi on duodenal biopsies to that of largely extraintestinal, subtle, or mild symptoms. Along with these changes, unexpectedly a new parallel entity appeared a few years ago and is gaining ground: the so-called nonceliac gluten sensitivity, an improper name because it should actually be referred to as wheat intolerance syndrome given that the role of gluten in all such cases is far from demonstrated and the implication of an immune involvement suggested by the term "sensitivity" is still unfounded. Lastly, wheat can be an offender also through an immunoglobulin E-mediated allergy, whose presence must also be evaluated and ruled out in selected cases.The practicing physician is therefore now challenged with the task of discerning which patients need to be assessed for one or the other of these disorders, and how.This review aims at providing an updated, critical reassessment of these 2 entities.
Brandt, Katia G; Silva, Giselia A P; Antunes, Margarida M C
To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.
Tian, Na; Messana, Irene; Leffler, Daniel A.; Kelly, Ciaran P.; Hansen, Joshua; Cabras, Tiziana; D'Alessandro, Alfredo; Schuppan, Detlef; Castagnola, Massimo; Helmerhorst, Eva J.
Purpose Gluten proteins, the culprits in celiac disease (CD), show striking similarities in primary structure with human salivary proline-rich proteins (PRPs). Both are enriched in pro-line and glutamine residues that often occur consecutively in their sequences. We investigated potential differences in the spectrum of salivary PRPs in health and CD. Experimental design Stimulated salivary secretions were collected from CD patients, patients with refractory CD, patients with gastrointestinal complaints but no CD, and healthy controls. PRP isoforms/peptides were characterized by anionic and SDS-PAGE, PCR, and LC-ESI-MS. Results The gene frequencies of the acidic PRP isoforms PIF, Db, Pa, PRP1, and PRP2 did not differ between groups. At the protein level, PRPs peptides showed minor group differences, but these could not differentiate the CD and/or refractory CDs groups from the controls. Conclusions and clinical relevance This extensive study established that salivary PRPs, despite similarity to gluten proteins, show no apparent correlation with CD and thus will not serve as diagnostic markers for the disease. The structural basis for the tolerance to the gluten-like PRP proteins in CD is worthy of further exploration and may lead to the development of gluten-like analogs lacking immunogenicity that could be used therapeutically. PMID:25726832
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.
van den Broeck, Hetty C; Cordewener, Jan H G; Nessen, Merel A; America, Antoine H P; van der Meer, Ingrid M
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.
Elli, Luca; Discepolo, Valentina; Bardella, Maria T; Guandalini, Stefano
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.
Fathi, Fariba; Ektefa, Fatemeh; Arefi Oskouie, Afsaneh; Rostami, Kamran; Rezaei-Tavirani, Mostafa; Houshang Mohammad Alizadeh, Amir; Tafazzoli, Mohsen
Aim The aim of this study is to look for the proper methods that would be a major step towards untreated CD diagnosis and seek the metabolic biomarkers causes of CD and compare them to control group. Background Celiac disease (CD) is a common autoimmune disorder that is not easily diagnosed using the clinical tests. Patients and methods Thirty cases and 30 controls were entered into this study. Metabolic profiling was obtained using proton nuclear magnetic resonance spectroscopy (1HNMR) to seek metabolites that are helpful for the detection of CD. Classification of CD and healthy subject was done using random forest (RF). Results The obtained classification model showed an 89% correct classification of CD and healthy subject for the external test set. The metabolites that caused changes in people with CD were identified using RF; these metabolites include lactate, valine and lipid. Conclusion The findings of the present study reveal serum lactate, valin and lipid levels in CD patient are lower than healthy cohorts. This metabolite may provide diagnostic tools as well as insight into potential targets for disease therapy. PMID:24834271
Francavilla, R; Cristofori, F; Stella, M; Borrelli, G; Naspi, G; Castellaneta, S
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
Esmaeilzadeh, Abbas; Ganji, Azita; Goshayeshi, Ladan; Ghafarzadegan, Kamran; Afzal Aghayee, Mehdi; Mosanen Mozafari, Homan; Saadatniya, Hassan; Hayatbakhs, Abdolrasol; Ghavami Ghanbarabadi, Vahid
BACKGROUND Delay in diagnosis of celiac disease (CD) occurs frequently, although its consequences are mostly not known. One of the presented symptoms in pediatric patients with CD is the short stature. However, far too little attention has been paid to physical features including height of adult patients with CD. This study was undertaken to evaluate whether patients suffering from CD are shorter in comparison with the general population without CD. As well, we evaluated probable correlations between demographic and physical features, main complains, serum anti tTG level, and intestinal pathology damage between short (lower quartile) versus tall stature (upper quartile) patients with CD. METHODS This was a retrospective cross-sectional study on 219 adult patients diagnosed as having CD in the Celiac Disease Center, between June 2008 and June 2014 in Mashhad, Iran. The exclusion criteria were ages less than 18 and more than 60 years. Height was compared with a group of 657 age- and sex matched control cases from the healthy population. The probable influencing factors on height such as intestinal pathology, serum level of anti-tissue transglutaminase(anti-tTG), serum vitamin D, and hemoglobin level at the time of diagnosis were assessed and were compared in short (lower quartile) versus tall stature (upper quartile) patients with CD. RESULTS Both male (n=65) and female (n=154) patients with CD were shorter than their counterpart in the general population (males: 168.5±8.6 to 171.3±7.2cm, p <0.01 and females: 154.8±10.58 to 157.8±7.2 cm, p <0.01). Spearman linear correlation showed height in patient with CD was correlated with serum hemoglobin (p <0.001, r=0.285) and bone mineral density (p<0.001) and not with serum vitamin D levels (p =0.024, r=0.237), but was not correlated with anti-tTG serum levels (p=0.97). CD patients with upper and lower quartile of height in men and women had no significant difference in the anti-tTG level and degree of duodenal pathology
García-Manzanares, Álvaro; Lucendo, Alfredo J; González-Castillo, Sonia; Moreno-Fernández, Jesús
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
Sitkin, S I; Tkachenko, E I; Vakhitov, T Ia; Oreshko, L S; Zhigalova, T N
Metabolomics is the emerging science of measurement and analysis of metabolome--the complete set of low molecular weight compounds in a cell, tissue, organ or whole organism. One of the aims of metabolomics is to research the response of an organism to a pathophysiological insult by measuring the concentrations of small molecule metabolites in biofluids and tissues and its dynamics. Intestinal microbiota is most probably involved in the development and maintenance of autoimmune inflammation in ulcerative colitis and celiac disease. Gas chromatography-mass spectrometry (GC - MS) of serum generates comprehensive metabolic profiles, reflecting integrated human (systemic) and gut microbial metabolism which may be altered in disease states. The aim of this study was to investigate GC - MS-based serum metabolomic profiles in UC and CD patients. Serum metabolic profiles were collected from 75 individuals: 20 patients with mild-moderate active UC, 35 CD patients, and 20 healthy controls (HC). We characterized 84 serum metabolites by use GC-MS. 18 metabolites at least have a combined (human + microbial) origin. In serum of UC patients, phenylacetic acid (PAA), 4-hydroxyphenylacetic acid (4-HPAA), 3-indolylacetic acid (IAA), succinic acid (SA) and fumaric acid (FA) were the metabolites most prominently increased, whereas 3-phenylpropionic acid (PPA) was significantly decreased. Serum of CD patients showed significant increases in IAA, 3-indolepropionic acid (IPA), SA and FA. Increased serum levels of succinic acid suggest its possible damaging effect on intestinal mucosa especially in ulcerative colitis. Orally administered butyrate + inulin as supplement to mesalazine in UC or gluten free diet in CD was effective in reducing disease activity with a marked improvement of serum metabolomic profiles (including SA reduction) and gut microbiota in both diseases. There were no any adverse events.
Sun, Xin; Lu, Li; Yang, Rong; Li, Yanbin; Shan, Ling; Wang, Yang
The prevalence of thyroid disease is likely increased among individuals with celiac disease (CD). In addition, exposure to gluten-free treatment may be associated with a risk of thyroid disease, but this association remains controversial. A systematic review was performed to evaluate the association between thyroid disease and CD. The articles were obtained from the PubMed, Web of Science, Embase, and Chinese WanFang bibliographical databases for the period up to May 2016. The results were analysed in a meta-analysis with odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). There were 13 articles in this meta-analysis, including 15629 CD cases and 79342 controls. Overall, the prevalence of thyroid disease in patients with CD was significantly increased compared with that in the control groups (OR 3.08, 95% CI 2.67–3.56, P<0.001). Moreover, there was no significant difference in the OR between the gluten-treated and untreated groups (OR 1.08, 95% CI 0.61–1.92, P = 0.786). The results of our meta-analysis support the hypothesis that the prevalence of thyroid disease in patients with CD is increased compared with that in controls, which suggests that CD patients should be screened for thyroid disease. The effect of gluten-free treatment on thyroid disease needs further investigation. PMID:28030626
Abraham, Gad; Tye-Din, Jason A.; Bhalala, Oneil G.; Kowalczyk, Adam; Zobel, Justin; Inouye, Michael
Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA testing can exclude diagnosis but has low specificity, providing little information suitable for clinical risk stratification. Using six European cohorts, we provide a proof-of-concept that statistical learning approaches which simultaneously model all SNPs can generate robust and highly accurate predictive models of CD based on genome-wide SNP profiles. The high predictive capacity replicated both in cross-validation within each cohort (AUC of 0.87–0.89) and in independent replication across cohorts (AUC of 0.86–0.9), despite differences in ethnicity. The models explained 30–35% of disease variance and up to ∼43% of heritability. The GRS's utility was assessed in different clinically relevant settings. Comparable to HLA typing, the GRS can be used to identify individuals without CD with ≥99.6% negative predictive value however, unlike HLA typing, fine-scale stratification of individuals into categories of higher-risk for CD can identify those that would benefit from more invasive and costly definitive testing. The GRS is flexible and its performance can be adapted to the clinical situation by adjusting the threshold cut-off. Despite explaining a minority of disease heritability, our findings indicate a genomic risk score provides clinically relevant information to improve upon current diagnostic pathways for CD and support further studies evaluating the clinical utility of this approach in CD and other complex diseases. PMID:24550740
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
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
Cenit, María Carmen; Olivares, Marta; Codoñer-Franch, Pilar; Sanz, Yolanda
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.
Hegenbart, Sebastian; Uhl, Andreas; Vécsei, Andreas
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
Trigoni, Evagelia; Tsirogianni, Alexandra; Pipi, Elena; Mantzaris, Gerassimos; Papasteriades, Chryssa
The increasing prevalence of celiac disease (CD), especially in adults, its atypical clinical presentation, and the strict, lifelong adherence to gluten-free diet (GFD) as the only option for healthy state create an imperative need for noninvasive methods that can effectively diagnose CD and monitor GFD. Aim. Evaluation of anti-endomysium (EmA) and anti-tissue transglutaminase IgA (tTG-A) antibodies in CD diagnosis, GFD monitoring, and first degree relatives screening in CD adult patients. Methods. 70 newly diagnosed Greek adult patients, 70 controls, and 47 first degree relatives were tested for the presence of EmA and tTG-A. The CD patients were monitored during a 3-year period. Results. EmA predictive ability for CD diagnosis was slightly better compared to tTG-A (P = 0.043). EmA could assess compliance with GFD already from the beginning of the diet, while both EmA and tTG-A had an equal ability to discriminate between strictly and partially compliant patients after the first semester and so on. Screening of first degree relatives resulted in the identification of 2 undiagnosed CD cases. Conclusions. Both EmA and tTG-A are suitable markers in the CD diagnosis, in the screening of CD among first degree relatives, having also an equal performance in the long term monitoring.
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.
Ungprasert, Patompong; Wijarnpreecha, Karn; Kittanamongkolchai, Wonngarm
Background and Objectives: The possible association between psoriasis and celiac disease (CD) has long been observed, but epidemiologic studies attempting to characterize this association have yielded inconclusive results. This meta-analysis was conducted with the aims to summarize all available data. Methods: We conducted a systematic review and meta-analysis of observational studies that reported relative risk, hazard ratio, odds ratio (OR), or standardized incidence ratio with 95% confidence interval (CI) comparing the risk of CD in patients with psoriasis versus participants without psoriasis. Pooled risk ratio and 95% CI were calculated using random-effect, generic inverse-variance methods of DerSimonian and Laird. Results: Four retrospective cohort studies with 12,912 cases of psoriasis and 24,739 comparators were included in this meta-analysis. The pooled analysis demonstrated a significantly higher risk of CD among patients with psoriasis compared with participants without psoriasis with the pooled OR of 3.09 (95% CI, 1.92–4.97). Limitations: Most primary studies reported unadjusted estimated effect, raising a concern over confounders. Conclusions: Our meta-analysis demonstrated an approximately 3-fold increased risk of CD among patients with psoriasis. PMID:28216724
Myers, Stephen P.; Rolfe, Margaret
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
Finsterer, J; Leutmezer, F
Abstract Objectives: Due to the similarity in the clinical presentation, morphology, and course, celiac disease (CD) may be mixed up with other immunological disorders, such as multiple sclerosis (MS). Case report: In a 43-year-old Caucasian male with a history of diarrhea and colics since young age, progressive sensory disturbances developed since age 18 years. At age 34, he was diagnosed as relapsing-remitting MS upon an inflammatory CSF-syndrome and non-specific white matter lesions and treated with interferon beta-1b during the next 8 years without effect. At age 35, axonal polyneuropathy and ataxia were diagnosed. Despite normal anti-gliadin, endomysial, and transglutaminase antibodies, CD was diagnosed at age 41, based upon the history, polyneuropathy, positivity for HLA-DQ2 and HLA-DQ8, the white matter lesions, and a beneficial response of the gastrointestinal problems and polyneuropathy to gluten-free diet. Conclusions: CD may mimic MS and may be present despite the absence of anti-gliadin, endomysial or transglutaminase antibodies. CD should be considered if there is a gastrointestinal problem, polyneuropathy, and ataxia, even if CSF and MRI findings are suggestive of MS. PMID:25408772
Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H
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
Zhao, Zhiyuan; Miao, Dongmei; Waugh, Kathleen; Taki, Iman; Dong, Fran; Liu, Edwin
Higher sensitive transglutaminase autoantibody (TGA) assay will detect the onset of celiac disease (CD) autoimmunity earlier. In developing a nonradioactive assay for TGA, we utilized electrochemiluminescence (ECL) technology and compared it to a high-performance radioimmunoassay (RIA) currently being used to screen patients with type 1 diabetes (T1D) and genetically at-risk individuals for CD. We selected 183 T1D patients with 60 patients having received biopsy and analyzed 396 sequential samples from 73 young children longitudinally followed up with TGA seroconversion, with 27 undergoing biopsy. In addition, 112 age-matched healthy control subjects were included in the study. With the 99th percentile of specificity, the ECL assay detected significantly more TGA positivity among patients with T1D (133/183) than RIA (114/183) and more of the sequential samples (34%) from 73 children than RIA (18%). The TGA assay performed by ECL was positive in all 59 subjects with villous atrophy. Among 73 longitudinally followed up children, ECL assay had earlier detection of TGA on 34 children by a mean of 2.5 years. In conclusion, the new TGA assay by ECL has a higher sensitivity than the current RIA assay and may better predict the onset of CD. PMID:28127566
Pascual, V; Medrano, L M; López-Palacios, N; Bodas, A; Dema, B; Fernández-Arquero, M; González-Pérez, B; Salazar, I; Núñez, C
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.
Rosales-Rivera, Luis Carlos; Dulay, Samuel; Lozano-Sánchez, Pablo; Katakis, Ioanis; Acero-Sánchez, Josep Lluís; O'Sullivan, Ciara K
A simple and rapid immunosensor for the determination of the celiac disease-related antibody, anti-tissue transglutaminase, was investigated. The antigenic protein tissue transglutaminase was chemically modified, introducing disulfide groups through different moieties of the molecule (amine, carboxylic, and hydroxyl groups), self-assembled on gold surfaces, and used for the detection of IgA and IgG autoantibodies. The modified proteins were evaluated using enzyme-linked immunosorbent assay and surface plasmon resonance, which showed that only introduction of the disulfide groups through amine moieties in the tissue transglutaminase preserved its antigenic properties. The disulfide-modified antigen was co-immobilized via chemisorption with a poly(ethylene glycol) alkanethiol on gold electrodes. The modified electrodes were then exposed to IgA anti-tissue transglutaminase antibodies and subsequently to horseradish peroxidase-labeled anti-idiotypic antibodies, achieving a detection limit of 260 ng ml(-1). Immunosensor performance in the presence of complex matrixes, including clinically relevant serum reference solutions and real patient samples, was evaluated. The introduction of disulfides in the antigenic protein enabled a simple and convenient one-step surface immobilization procedure involving only spontaneous gold-thiol covalent binding. Complete amperometric assay time was 30 min.
Bottasso Arias, Natalia M.; García, Marina; Bondar, Constanza; Guzman, Luciana; Redondo, Agustina; Chopita, Nestor; Córsico, Betina; Chirdo, Fernando G.
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
Shahryar, Mosayeb; Shahramian, Iraj; Dehghani, Seyed Mohsen; Noori, NoorMohammad; Ataollahi, Maryam
Lithophagia is a type of pica that might be resulted from Iron Deficiency Anemia (IDA) which is the frequent presenting signs of Celiac Disease (CD). A 5-year-old child with a two year history of the lithophagia with a, refractory IDA, abdominal distention and constipation. The child did not grow well and had failure to thrive. With suspicion to CD, TTg IgA level was measured and due to an incearse of TTg IgA level the patients were undergone esophagogastrodeudonoscpy and jejunal biopsy. The biopsy showed severe villous atrophy and an increase in limphoplasma cells. Biopsy confirmed diagnosis of CD and glutten free diet was initiated finally. Six months after diagnosis and commencing the gluten free diet, the lithophagia and constipation in patient eradicated completely. IDA and failure to thrive were improved and the level of TTg IgA was reached to the normal. The case demonstrated the relationship between lithophagia and CD in anemia. Therefore, in the same cases such as our case should be considered CD as the most important causes of lithophagia. PMID:28331568
Mohapatra, Suryanarayan; Arobelidze, Salome; Gundelly, Parveen; Changarath Vijayan, Anil Kumar
There is an increasing incidence of infective endocarditis secondary to central venous catheters, which is termed as 'healthcare-associated infective endocarditis'. There is an increased risk of getting infective endocarditis in conditions with malnutrition and also if the tip of the central venous catheter is deep in the right atrium close to the tricuspid valve. We present a case of 31-year-old female who had all these risk factors. She was admitted to the hospital for the work up of the weight loss and was diagnosed with celiac disease. Central venous access was obtained because of poor peripheral intravenous access via the peripherally inserted central catheter which was complicated by thrombosis and removed after three days of insertion, and she was started on anticoagulation. Two weeks after being discharged, she presented to the emergency department with fever, shortness of breath, and had signs of congestive heart failure. A computed tomography of the chest for pulmonary embolism was taken and showed small clot burden pulmonary embolism and two cavitary lesions in the right lung. A transthoracic echocardiogram was taken and showed vegetation on the tricuspid valve and blood cultures were positive for Staphylococcus aureus. Hence, a diagnosis of infective endocarditis was made, and she was treated with intravenous antibiotics for a total of six weeks after a long and complicated hospital stay. PMID:28348945
Ravelli, Alberto; Villanacci, Vincenzo
Currently, the diagnosis of celiac disease (CD) is based upon the combination of raised serum anti-tissue transglutaminase or anti-endomysial antibodies and the presence of histological alterations of variable degree in the duodenal mucosa. Interpretation of duodenal biopsies is subjected to a number of variables, and the lack of standardization may cause diagnostic controversy or even misdiagnosis. The aim of this overview is to solicit a standardization of the procedures of biopsy taking, orientation, processing, staining and interpretation in order to avoid or minimize misinterpretation of duodenal biopsies. Based on a literature review and extensive personal experience, the appropriate methodology of duodenal biopsy taking, orientation, fixation, processing, staining and interpretation was thoroughly reviewed, and the most common and relevant errors and artifacts were identified. To maximize the diagnostic yield of duodenal biopsy in CD, multiple specimens are best taken from different sites of the duodenum during endoscopy, and careful visual inspection of the duodenal mucosa may help identify abnormalities related to villous atrophy. Biopsy handling and orientation are of utmost importance to avoid artifacts that may impair the pathologist's ability to detect pathology and normality. Immunostaining with anti-CD3 monoclonal antibody should be carried out, and a simplified histological classification may help distinguish atrophic from non-atrophic stages of CD enteropathy. Meticulous attention to biopsy orientation, handling and processing - together with the knowledge of the most common histological artifacts - is necessary to avoid a wrong histological interpretation which, in turn, may lead to misdiagnosis in CD.
Mehta, Pooja; Furuta, Glenn T.
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
Soler, Maria; Estevez, M-Carmen; Moreno, Maria de Lourdes; Cebolla, Angel; Lechuga, Laura M
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.
Carrasco, Anna; Ibarra, Montserrat; Temiño, Rocío; Salas, Antonio; Esteve, Maria
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
Kotze, L M; Utiyama, S R; Nisihara, R M; Mocelin, V; Carvalho, R F; Zeni, M P; Amarante, H M
Sensibility to gluten is a condition with high immunological reaction against gluten proteins from wheat, barley, rye and oats in individuals genetically susceptible. Celiac disease is its most frequent expression with various forms of clinical presentation. The treatment consists in gluten free diet. Although the biopsy of proximal small bowel is necessary, the importance of serological tests is increasing in the screening, diagnosis and monitoring of gluten free diet in celiac patients. The aim of this study was to investigate the presence of antiendomysium (EmA-IgA) and anti-reticulin (ARA-IgA) antibodies in 56 celiac patients (17 at diagnosis, 24 adherent to the diet and 15 with transgression to the diet). The antibodies were detected by indirect immunofluorescence, using human umbilical cord as substrate for the EmA-IgA and rat liver and kidney for the ARA-IgA. In the patients at diagnosis and in the group with transgression to the diet the total positivity was 100% for EmA-IgA and 59.4% for ARA-IgA. Antibodies were not detected in gluten-free diet patients. Among the 32 positive patients, the concordance of both tests was of 59.4% (19/32), being 40.6% (13/32) negative to ARA-IgA and positive to EmA-IgA. No patient was positive for ARA-IgA and negative for EmA-IgA. Thus, the sensitivity for EmA-IgA was of 100% and 59.4% for ARA-IgA. The association of the two tests did not improve the positivity in the samples. In conclusion, EmA-IgA can be considered the best serological test for diagnosis and follow up of celiac patients, because it presents high predictive value, high specificity and sensibility and is not expensive if using human umbilical cord as substrate.
Sams, Aaron; Hawks, John
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.
Sharma, Shiv Dayal; Gupta, Rajkumar; Goyal, Alok; Sharma, Aakash
Purpose To study whether breastfeeding and breastfeeding status during gluten introduction influences the age at diagnosis of celiac disease (CD). In addition to study, whether the timing of gluten introduction influences the age at diagnosis of CD. Methods It was a hospital based observational study. Total 198 patients diagnosed with CD as per modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition (2012) criteria, aged between 6 months to 6 years were included. Detail history taken with special emphasis on breastfeeding and age of gluten introduction. Standard statistical methods used to analyze the data. Results Mean±standard deviation age of onset and diagnosis of CD in breastfed cases was 2.81±1.42 years and 3.68 ±1.55 years respectively as compared to 1.84±1.36 years and 2.70±1.65 years respectively in not breastfed cases (p<0.05). Those who had continued breastfeeding during gluten introduction and of longer duration had significantly delayed onset of disease. The age at onset of CD was under one year in 40.42% of the cases, who had started gluten before 6 months of age compared to only 12.58% of those who had started gluten later (p<0.001). The proposed statistical model showed that two variables, i.e., breast feeding status during gluten introduction and age at gluten introduction positively influencing the age at diagnosis of CD. Conclusion Delayed gluten introduction to infant's diet along with continuing breastfeeding, delays symptomatic CD. However, it is not clear from our study that these infant feeding practices provide permanent protection against the disease or merely delays the symptoms. PMID:28090467
Maidana, Juan Pablo; Corzo, Josefina; Molina, Carolina; Etcheverry, María Ester; Calli, Rogelio; Habra, Eugenia; Caillou, Ernesto; Alabarse, Graciela; Guinudinik, Alejandra; Cardozo, Ruben; Manso, Viviana; Posleman, Sara Emilia; Araujo, Carmen Rosa
Celiac disease is a systemic autoimmune disease that affects 1.26% of the Argentine pediatric population. Our purpose was to study the prevalence of specific antibodies of celiac disease in a risk group and to find the association with specific factors. This was a cross-sectional study conducted in children ofa Nutritional Recovery Program from 1 year and 9 months to 6 years and 9 months old, from one Health Area of Tucumán Province, during 2010 and 2011, in a random cluster sample. It was studied a population of 175 children. We identified 3 cases with positive serology, equivalent to 1.7% of the study population. The association between cases with positive serology for celiac disease and other variables referred could not be established.
Ghozzi, Mariam; Sakly, Wahiba; Mankaï, Amani; Bouajina, Elyes; Bahri, Fethi; Nouira, Rafiaa; Kechrid, Chedia; Ghedira, Ibtissem
Celiac disease (CD) is an autoimmune systemic disease characterized by not only gastrointestinal but also extraintestinal manifestations. The aim of our study was to do a serological screening for CD, by IgA endomysial antibodies (EmA), in patients with unexplained articular manifestations. Two hundred and eleven patients suffering from arthritis or arthralgia without evident cause were studied. EmA were determined by indirect immunofluorescence on human umbilical cord. Two thousand and five hundred blood donors served as control group. Out of 211 patients, 5 had EmA (2.37 %). The frequency of EmA in our patients was significantly higher than in the control group (2.37 vs. 0.28 %, p < 0.01). All patients with positive EmA were female. EmA were significantly more frequent in female patients than in female healthy subjects (3 vs. 0.4 %, p < 0.01). Medical records revealed: diarrhea (one patient), short size (one patient), anemia (three patients), weight loss (two patients) spontaneous abortion (three patients), secondary amenorrhea (one patient), early menopause (one patient) and early baby death (one patient). Biochemical analysis showed decreased level of calcium (one patient), vitamin D (one patient) and cholesterol (one patient). Unexplained liver cytolysis was observed in two patients. Radiological examination showed demineralization of two hands in one patient. Bone osteodensitometry done in one patient out of five revealed lumbar osteopenia. The articular manifestations of the five patients did not respond to corticosteroid treatment. CD must be considered among the differential diagnosis in a patient with arthritis or arthralgia.
Marafini, Irene; Monteleone, Ivan; Di Fusco, Davide; Sedda, Silvia; Cupi, Maria Laura; Fina, Daniele; Paoluzi, Alessandro Omero; Pallone, Francesco; Monteleone, Giovanni
Introduction and Aim Natural killer (NK) cells are a first line of defence against viruses and down-regulation of NK cell cytotoxic receptors represents one of the strategies by which viruses escape the host’s immune system. Since onset of celiac disease (CD), a gluten-driven enteropathy, has been associated with viral infections, we examined whether CD-associated inflammation is characterized by abnormal distribution of NK cell receptors involved in recognition of viral-infected cells. Materials and Methods Intraepithelial mononuclear cells, isolated from duodenal biopsies of active and inactive CD patients and healthy controls (CTR) and jejunal specimens of obese subjects undergoing gastro-intestinal bypass, were analysed for NK cell markers by flow-cytometry. Expression of granzyme B, interleukin (IL)-22 and tumor necrosis factor (TNF)-α was as assessed in freshly isolated and toll-like receptor (TLR) ligand-stimulated cells. Results The percentages of total NK cells and NKT cells did not significantly differ between CD patients and CTR. In active CD, the fractions of NKp30+ NK cells, NKG2D+ NK cells and NKG2D+ NKT cells were significantly increased as compared to inactive CD patients and CTR. In contrast, CD-associated inflammation was marked by diminished presence of NKG2A+ NK cells and NKG2A+ NKT cells. The fractions of NK cells and NKT cells expressing either NKp44 or NKp46 did not differ between CD and controls, but in CD less NK cells and NKT cells co-expressed these receptors. NKp44/NKp46-double positive cells produced granzyme B and IL-22 but not TNF-α and responded to TLR ligands with enhanced expression of granzyme B. Conclusions These data indicate that active phase of CD associates with reduced presence of NKp44/NKp46-double positive NK cells and NKT cells in the epithelial compartment. PMID:27171408
Boschee, Erin D; Yap, Jason Y K; Turner, Justine M
AIM To determine the sensitivity of macroscopic appearance for predicting histological diagnosis at sites other than duodenum in pediatric celiac disease (CD). METHODS Endoscopic and histologic findings in pediatric patients undergoing upper endoscopy for first-time diagnosis of CD at Stollery Children’s Hospital from 2010-2012 were retrospectively reviewed. RESULTS Clinical charts from 140 patients were reviewed. Esophageal and gastric biopsies were taken in 54.3% and 77.9% of patients, respectively. Endoscopic appearance was normal in the esophagus and stomach in 75% and 86.2%. Endoscopic esophageal diagnoses were eosinophilic esophagitis (EE) (11.8%), esophagitis (7.9%), glycogenic acanthosis (1.3%) and non-specific abnormalities (3.9%). Endoscopic gastric diagnoses were gastritis (8.3%), pancreatic rest (0.9%), and non-specific abnormalities (4.6%). Histology was normal in 76.3% of esophageal and 87.2% of gastric specimens. Abnormal esophageal histology was EE (10.5%), esophagitis (10.5%), glycogenic acanthosis (1.3%) and non-specific (1.3%). Gastritis was reported in 12.8% of specimens. Sensitivity and specificity of normal endoscopy for predicting normal esophageal histology was 86.2% and 61.1%, and for normal gastric histology was 87.4% and 21.4%. CONCLUSION In the absence of macroscopic abnormalities, routine esophageal and gastric biopsy during endoscopy for pediatric CD does not identify major pathologies. These findings have cost and time saving implications for clinical practice. PMID:28216971
Marino, Mariacatia; Casale, Rossella; Borghini, Raffaele; Di Nardi, Sara; Donato, Giuseppe; Angeloni, Antonio; Moscaritolo, Salvatore; Grasso, Lorenza; Mazzarella, Giuseppe; Di Tola, Marco; Rossi, Mauro; Picarelli, Antonio
Celiac disease (CD) treatment requires a gluten-free diet (GFD), although alternative approaches have been proposed. Modification of gliadin peptides using microbial transglutaminase (mTG) inhibits their ability to induce immune response in vitro. Our aim was to evaluate the safety of mTG-modified wheat flour ingestion in CD patients. Twenty-one CD patients in remission were randomized to receive mTG-modified (n=11) or unmodified (n=10) wheat flour rusks, in double-blind fashion. Monthly, patients completed a symptom questionnaire. Serum anti-tTG, EMA and creatinine levels were monitored. At baseline and after 90days, serum anti-actin antibodies (AAA) were measured and upper endoscopy was performed. Data were analyzed by non-parametric tests. 7/11 patients eating modified rusks and 7/10 patients receiving unmodified rusks completed the study. At baseline, all patients showed negative serum anti-tTG and EMA results. At the end, 2/7 (28.6%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented positive serum anti-tTG and EMA results. Creatinine results were unmodified. Moreover, 1/7 (14.3%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented villous atrophy. In patients who received unmodified rusks, the AAA levels increased significantly and duodenal anti-tTG levels appeared higher than those measured in patients who ate modified rusks. Abdominal swelling, bloating and nausea were more severe in patients ingesting unmodified rusks than those taking modified rusks. Our results may support larger clinical trials to confirm the enzymatic treatment of wheat flour as an alternative to GFD. Clinicaltrials.gov registration no: NCT02472119.
Silano, Marco; Agostoni, Carlo; Sanz, Yolanda; Guandalini, Stefano
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
Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Carlos
Introduction Celiac disease (CD) prevalence is increasing but the disorder remains undiagnosed. The study compares CD serology markers requested by General Practitioners (GPs) over time and geographical areas. The aim of the current research is to assess the inter-practice and temporal variability in the request of CD serology markers by GPs in Spain, and the differences between regions. Materials and methods A cross-sectional study was conducted enrolling Spanish clinical laboratories. Primary care CD serology markers request in 2010, 2012 and 2014 from 15 autonomous communities (AACC), with more participants was reported. Test-utilization rates were calculated (tissue transglutaminase IgA antibodies (tTG-IgA) and deaminated peptide gliadine IgA antibodies (DGP-IgA) per 1000 inhabitants), and also the ratio of both tests request (DGP-IgA /tTG-IgA). Results The request of tTG-IgA per 1000 inhabitants increased significantly along years (from 3.99 to 5.90 (P < 0.001)). The demand of DGP-IgA per 1000 inhabitants was maintained in 2010 and 2012 (0.68 and 0.6), and decreased in 2014 (0.35) (P = 0.927). DGP-IgA /tTG-IgA diminished over time (from 0.16 to 0.06 (P = 0.548)), and in the 2014 edition, there was a significant regional difference, ranging from 0.01 to 0.57 (P < 0.001). Conclusions The variability in the request in CD serology markers emphasizes the need of inter-regional cooperation to develop strategies to optimize the use of laboratory tests. PMID:28392744
Wierdsma, Nicolette J.; van Bokhorst-de van der Schueren, Marian A. E.; Berkenpas, Marijke; Mulder, Chris J. J.; van Bodegraven, Ad A.
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
López-Palacios, N.; Bodas, A.; Dema, B.; Fernández-Arquero, M.; González-Pérez, B.; Salazar, I.; Núñez, C.
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
Reilly, Norelle R; Lebwohl, Benjamin; Mollazadegan, Kaziwe; Michaëlsson, Karl; Green, Peter HR; Ludvigsson, Jonas F
Objectives To examine the risk of any fractures in patients with both type 1 diabetes (T1D) and celiac disease (CD) vs patients with T1D only. Study design We performed a population-based cohort study. We defined T1D as individuals aged ≤30 years who had a diagnosis of diabetes recorded in the Swedish National Patient Register between 1964–2009. Individuals with CD were identified through biopsy report data between 1969–2008 from any of Sweden’s 28 pathology departments. Some 958 individuals had both T1D and CD and were matched for sex, age and calendar period with 4,598 reference individuals with T1D only. We then used a stratified Cox regression analysis, where CD was modeled as a time-dependent covariate, to estimate the risk of any fractures and osteoporotic fractures (hip, distal forearm, thoracic and lumbar spine, and proximal humerus) in patients with both T1D and CD compared with that in patients with T1D only. Results During follow-up, 12 patients with T1D and CD had a fracture (1 osteoporotic fracture). CD did not influence the risk of any fracture (adjusted Hazard Ratio=0.77; 95%CI=0.42–1.41) or osteoporotic fractures (adjusted Hazard Ratio=0.46; 95%CI=0.06–3.51) in patients with T1D. Stratification for time since CD diagnosis did not affect risk estimates. Conclusion Having a diagnosis of CD does not seem to influence fracture risk in young patients with T1D. Follow-up in this study was, however, too short to ascertain osteoporotic fractures which traditionally occur in old age. PMID:26589343
Fouda, Mona A; Khan, Aliya A; Sultan, Muhammad; Rios, Lorena P; McAssey, Karen; Armstrong, David
OBJECTIVE: To review the evaluation and management of skeletal health in patients with celiac disease (CD), and to make recommendations on screening, diagnosis, treatment and follow-up of low bone mineral density (BMD) in CD patients. METHODS: A multidisciplinary team developed clinically relevant questions for review. An electronic search of the literature was conducted using the MEDLINE and EMBASE databases from 1996 to 2010. All original studies, reviews and guidelines, both pediatric and adult, were included. A document summarizing the results of the review and proposed recommendations was prepared and underwent multiple revisions until consensus was reached. RESULTS: At diagnosis, approximately one-third of adult CD patients have osteoporosis, one-third have osteopenia and one-third have normal BMD. Children with CD have low bone mass at diagnosis. Adult and pediatric CD patients are at increased risk of fractures. DISCUSSION: For adults, serum calcium, albumin, 25(OH) vitamin D3, parathyroid hormone and 24 h urine calcium testing should be performed at diagnosis; patients with ‘classic’ CD and those at risk for osteoporosis should undergo a dual x-ray absorptiometry scan. An abnormal baseline dual x-ray absorptiometry scan should be repeated one to two years after initiation of a gluten-free diet (GFD). For children, BMD should be assessed one year after diagnosis if GFD adherence is not strict. A GFD is the most important treatment for bone loss. Supplemental antiresorptives may be justified in those who remain at high fracture risk (eg, postmenopausal women, older men) after implementation of a GFD. CONCLUSION: Current evidence does not support the screening of all CD patients for low BMD at diagnosis. Follow-up BMD assessment should be performed one to two years after initiation of a GFD. PMID:23166906
Boschetto, Davide; Di Claudio, Gianluca; Mirzaei, Hadis; Leong, Rupert; Grisan, Enrico
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).
Sugai, Emilia; Moreno, María L; Hwang, Hui J; Cabanne, Ana; Crivelli, Adriana; Nachman, Fabio; Vázquez, Horacio; Niveloni, Sonia; Argonz, Julio; Mazure, Roberto; Motta, Graciela La; Caniggia, María E; Smecuol, Edgardo; Chopita, Néstor; Gómez, Juan C; Mauriño, Eduardo; Bai, Julio C
AIM: To establish the diagnostic performance of several serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential serological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects. PMID:20593499
van den Broeck, Hetty C; America, Antoine H P; Smulders, Marinus J M; Bosch, Dirk; Hamer, Rob J; Gilissen, Ludovicus J W J; van der Meer, Ingrid M
The detection, analysis, and quantification of individual celiac disease (CD) immune responsive gluten proteins in wheat and related cereals (barley, rye) require an adequate and reliable extraction protocol. Because different types of gluten proteins behave differently in terms of solubility, currently different extraction protocols exist. The performance of various documented gluten extraction protocols is evaluated for specificity and completeness by gel electrophoresis (SDS-PAGE), immunoblotting and RIDASCREEN Gliadin competitive ELISA. Based on these results, an optimized, two-step extraction protocol has been developed.
Lamacchia, Carmela; Camarca, Alessandra; Picascia, Stefania; Di Luccia, Aldo; Gianfrani, Carmen
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.
Lamacchia, Carmela; Camarca, Alessandra; Picascia, Stefania; Di Luccia, Aldo; Gianfrani, Carmen
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
Linz, Christopher M.; Tsay, Julie L.; Jin, Ming; El-Dika, Samer S.
Celiac crisis is a rare presentation of celiac disease that is characterized by life-threatening electrolyte abnormalities, vitamin and mineral deficiencies, and diarrhea. Triggers for celiac crisis include major surgeries, pancreatitis, and infections of cytomegalovirus, and salmonella. A 24-year-old woman presented with celiac crisis associated with severe herpes simplex virus (HSV) esophagitis. This case demonstrates that nutritional deficiencies seen in celiac disease can result in a relative immunodeficiency, which may lead to other infectious complications. Additionally, early recognition of celiac crisis is imperative as the metabolic derangements may be life-threatening, and therapy with gluten restriction and nutritional repletion is effective. PMID:27921058
Bondar, Constanza; Araya, Romina E.; Guzman, Luciana; Rua, Eduardo Cueto; Chopita, Nestor; Chirdo, Fernando G.
Lymphocytic infiltration in the lamina propria (LP), which is primarily composed of CD4+ Th1 cells and plasma cells, and increased numbers of intraepithelial lymphocytes (IELs), is a characteristic finding in active celiac disease (CD). Signals for this selective cell recruitment have not been fully established. CXCR3 and its ligands, particularly CXCL10, have been suggested to be one of the most relevant pathways in the attraction of cells into inflamed tissues. In addition, CXCR3 is characteristically expressed by Th1 cells. The aim of this work was to investigate the participation of the chemokine CXCL10/CXCR3 axis in CD pathogenesis. A higher concentration of CXCL10 was found in the serum of untreated CD patients. The mRNA levels of CXCL10 and CXCL11 but not CXCL9 were significantly higher in duodenal biopsies from untreated CD patients compared with non-CD controls or treated patients. The results demonstrate that CXCL10 is abundantly produced in untreated CD and reduced in treated patients, and the expression of CXCL10 was found to be correlated with the IFNγ levels in the tissue. Plasma cells and enterocytes were identified as CXCL10-producing cells. Moreover, the CXCL10 expression in intestinal tissues was upregulated by poly I:C and IL-15. IELs, LP T lymphocytes, and plasma cells, which infiltrate the intestinal mucosa in untreated CD, express CXCR3. The CXCR3/CXCL10 signalling axis is overactivated in the small intestinal mucosa in untreated patients, and this finding explains the specific recruitment of the major cell populations that infiltrate the epithelium and the LP in CD. PMID:24586509
Zambon, Carlo-Federico; Navaglia, Filippo; Greco, Eliana; Pelloso, Michela; Artuso, Serena; Padoan, Andrea; Pescarin, Matilde; Aita, Ada; Bozzato, Dania; Moz, Stefania; Cananzi, Mara; Guariso, Graziella; Plebani, Mario
Background TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner. Methods 511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence). Results Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations. Conclusion TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk. PMID:25915602
Luján-Sanchis, Marisol; Pérez-Cuadrado-Robles, Enrique; García-Lledó, Javier; Juanmartiñena Fernández, José-Francisco; Elli, Luca; Jiménez-García, Victoria-Alejandra; Egea-Valenzuela, Juan; Valle-Muñoz, Julio; Carretero-Ribón, Cristina; Fernández-Urién-Sainz, Ignacio; López-Higueras, Antonio; Alonso-Lázaro, Noelia; Sanjuan-Acosta, Mileidis; Sánchez-Ceballos, Francisco; Rosa, Bruno; González-Vázquez, Santiago; Branchi, Federica; Ruano-Díaz, Lucía; Prieto-de-Frías, César; Pons-Beltrán, Vicente; Borque-Barrera, Pilar; González-Suárez, Begoña; Xavier, Sofía; Argüelles-Arias, Federico; Herrerías-Gutiérrez, Juan-Manuel; Pérez-Cuadrado-Martínez, Enrique; Sempere-García-Argüelles, Javier
AIM To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE). METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed. RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD. CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD. PMID:28216978
Sarcoidosis is a chronic idiopathic granulomatous disease. Interleukin-18 (IL-18) has been strongly implicated in the pathogenesis of sarcoidosis. Sarcoidosis shows characteristic microRNAs (miRNAs) profiles. MiRNAs have recently emerged as a new class of modulators of gene expression. MiRNAs are involved in susceptibility to a number of autoimmune diseases promoting and inhibiting the gene expression of different Th1 pro-inflammatory cytokines including IL18. Sarcoidosis has been connected with a variety of autoimmune disorders including celiac disease (CD). CD is a chronic, immune-mediated condition of the small intestine caused by permanent intolerance to dietary gluten. IL-18 has been reported to play an important role in inducing and maintaining inflammation after gluten exposure. MiRNAs expression is significantly altered in CD patients. We hypothesize that sarcoidosis and CD may be the result of common genetic variants in IL-18 miRNA target site.
Kapoerchan, Varsha V; Wiesner, Martina; Overhand, Mark; van der Marel, Gijs A; Koning, Frits; Overkleeft, Herman S
Celiac disease is an intestinal disease caused by intolerance for gluten, a common protein in food. A life-long gluten-free diet is the only available treatment. As it is well established that the interaction between proline-rich gluten derived peptides and the human HLA-DQ2 molecules induces immune responses that lead to disease development, we have now designed a series of gluten peptides in which proline residues were replaced by azidoprolines. These peptides were found to bind to HLA-DQ2 with an affinity similar to that of the natural gluten peptide. Moreover, some of these peptides were found to be non-immunogenic and block gluten induced immune responses. These can thus serve as lead compounds for the development of HLA-DQ2 blocker peptides.
Wang, Hongling; Zhou, Guoying; Luo, Linjie; Crusius, J. Bart A.; Yuan, Anlong; Kou, Jiguang; Yang, Guifang; Wang, Min; Wu, Jing; von Blomberg, B. Mary E.; Morré, Servaas A.; Peña, A. Salvador; Xia, Bing
Abstract Celiac disease (CD) is common in Caucasians, but thought to be rare in Asians. Our aim was to determine the prevalence of CD in Chinese patients with chronic diarrhea predominant irritable bowel syndrome (IBS-D). From July 2010 to August 2012, 395 adult patients with IBS-D and 363 age and sex-matched healthy controls were recruited in Zhongnan Hospital of Wuhan University and Xiaogan Central Hospital in Hubei province, central China. Patients with IBS-D were diagnosed according to the Rome III criteria. Serum Immunoglobulin (IgA/IgG) anti-human tissue transglutaminase (anti-htTG)-deamidated gliadin peptide (DGP) antibodies were measured in a single ELISA (QUANTA Lite h-tTG/DGP Screen). Upper endoscopy with duodenal biopsies and HLA-DQA1 and HLA-DQB1 genotyping were performed in seropositive subjects and a gluten-free diet was prescribed. Seven IBS-D patients (7/395, 1.77%) and 2 healthy controls (2/363, 0.55%), were positive for anti-htTG/DGP antibodies. Of these 9 cases, 1 was lost to follow-up, 3 were suspected to have CD and 5 were eventually diagnosed as CD with intestinal histological lesions classified as Marsh Type II in 2 and Type III in 3. Of these 5 diagnosed CD patients, 4 (4/395, 1.01%) were from the IBS-D group and 1 (1/363, 0.28%) from the healthy control had asymptomatic CD. Two Type III CD patients with relatively high titers in the serologic assay were homozygous and heterozygous for haplotype HLA-DQA1∗03-DQB1∗03:03 (HLA-DQ9.3), respectively. In the present study, CD was present in 1.01% of patients with IBS-D and in 0.28% of the control group. We like to suggest that the haplotype HLA-DQA1∗03-DQB1∗03:03 (HLA-DQ9.3), which is common in Chinese, is a new susceptibility factor for CD in China. Larger screening and genetic studies are needed in the Chinese population of different regions. PMID:26496305
Background Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach. Methods The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology. Results Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively. Conclusions Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and
Background Smoking status has been linked to several chronic inflammatory conditions but earlier research on smoking and celiac disease (CD) is contradictive. There are little data on moist snuff use and CD. The purpose of this study was to investigate the association between smoking, moist snuff use and later CD. Methods We identified individuals with biopsy-verified CD (villous atrophy, histopathology stage Marsh III) through biopsy-reports from Sweden’s 28 pathology departments. Data on smoking and moist snuff were collected from the Swedish construction worker database “Bygghälsan” that includes preventive health care check-up data. Through poisson regression we calculated relative risks (RRs) for later CD according to smoking status (n = 305,722), and moist snuff status (n = 199,200) adjusting for age, sex and decade. Results During follow-up 488 individuals with smoking data, and 310 with moist snuff data had a diagnosis of CD. The risk of CD was independent of smoking status with all RRs being statistically insignificant and ranging between 0.9 and 1.0. Compared to non-smokers, neither current smokers (RR = 0.93; 95% CI = 0.76-1.14) nor ex-smokers (RR = 0.98; 95% CI = 0.75-1.28) were at increased or decreased risk of CD. Risk estimates were similar in moderate smokers (RR = 0.92; 0.72-1.16) and heavy smokers (RR = 0.95; 0.74-1.24), and did not change when we examined the risk more than ten years after health examination (RR-moderate: 0.90; and RR-heavy: 0.95; both p > 0.05). Moist snuff use was not associated with later CD (RR = 1.00; 0.78-1.28), or with CD after more than ten years of follow-up (RR = 1.05; 0.80-1.38). Conclusions We found no association between smoking, moist snuff use and future CD. PMID:24994113
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...
Toft-Hansen, Henrik; Nielsen, Christian; Biagini, Matteo; Husby, Steffen; Lillevang, Søren T
The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA) staining for Gal-β(1,3)-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates.
Kotze, L M S
This study shows a broad analysis of gynaecological and obstetrical disturbances in patients with celiac disease in relation to their nutritional status and adherence to a gluten-free diet. Seventy-six adult celiac patients were analyzed according to nutritional status and 18 children/adolescents to gluten-free diet adherence. As controls, 84 adults and 22 adolescents with irritable bowel syndrome were used The significant findings were observed as follow: adult celiac patients, irrespective of the nutritional status, were younger than controls, presented delayed menarche, secondary amenorrhea, a higher percentage of spontaneous abortions, anemia and hypoalbuminemia. No differences were observed regarding the number of pregnancies, age at menopause and duration of the reproductive period. After treatment, patients presented with normal pregnancies and one patient presented spontaneous abortion. The adolescents who were not adherent to gluten-free diet presented delayed menarche and secondary amenorrhea. In conclusion, gluten per se could explain the disturbances and malnutrition would worsen the disease in a consequent vicious cycle. Therefore, celiac disease should be included in the screening of reproductive disorders.
Esposito, Francesco; Fasano, Evelina; Scognamiglio, Gelsomina; Nardone, Antonio; Triassi, Maria; Cirillo, Teresa
Fumonisins are mycotoxins produced by Fusarium species and affecting maize crops. Some analogues of fumonisins are known for their toxic and possible carcinogenic effects on humans and animals. Because of their occurrence in corn-based food, diet is the main source of exposure to these mycotoxins, especially among people affected by celiac disease. Hence, the purpose of this paper was to evaluate the amount of fumonisins B1, B2 and B3 in maize-based products and to assess the exposure of people affected by celiac disease to fumonisins. The sample consisted of 154 gluten-free products analyzed according to method UNI EN 14352:2005. Results showed a heterogeneous contamination by fumoninisin B1, B2 and B3, although below limits of Commission Regulation No 1126/2007 and consistent with other European literature data. Exposure to fumonisins was evaluated for different age groups. In some cases exposure to fumonisins could not be ignored since the total intake could exceed EFSA Provisional Maximum Tolerable Intake up to 150%. Therefore, in the light of an overall contamination by fumonisins the total dietary exposure could be underrated not only in people affected by celiac disease, but also in non-celiac population.
Cadahía, V; Rodrigo, L; Fuentes, D; Riestra, S; de Francisco, R; Fernández, M
We discuss the case of a 17-year-old male who at the age of 7 was diagnosed with celiac disease (CD) together with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). The patient was treated with gluten-free diet and immunosuppressive drugs (azathioprine), and currently remains asymptomatic. The patient's younger, 12-year-old sister was diagnosed with CD when she was 1.5 years old, and at 7 years she developed type-I diabetes mellitus, which was difficult to control. A family study was made, and both parents were found to be affected with silent CD. All were DQ2 (+). In relation to the case and family study, we provide a series of comments related to CD and its complications.
Beltran, S; Bony-Trifunovic, H; Gouilleux-Gruart, V; Djeddi, D; Dadamessi, I; Dupas, J L; Boudailliez, B
The aim of this study was to determine the prevalence of celiac disease (CD) markers in a French cohort of 84 children type 1 diabetics. Detection of antitransglutaminase (AtTG), antiendomysium (AEA) and antigliadin (AGA) antibodies was performed. Group 1 included 81 (96.4%) diabetic patients with negative antibodies. Group 2 included 3 patients (3.6%) with positive serological markers: 1 AGA-AEA-AtTG and 1 AEA-AtTG with proved histological diagnosis and 1 AGA positive with negative histology. No statistically significant difference was observed between the groups with regard to age, duration of diabetes, familial target stature, and ratios Height/Age and Weight/Height. Presence of CD serological markers was related to a lower level of HbA1c. Prevalence of CD serological markers is important in this French cohort but lower than other countries.
Khosravi, Asghar; Mansouri, Masoume; Rostami-Nejad, Mohammad; Shahbazkhani, Bijan; Ekhlasi, Golnaz; Kalantari, Ebrahim
Aim: The aim of this study was to evaluate the likelihood ratio and frequency of DQ2 and DQ8 in Iranian patients with celiac disease (CD). Background: The HLA DQ2 and HLA DQ8 are the important mediators in the development of celiac disease. A few studies evaluated the frequency of HLA DQ2 and HLA DQ8 haplotypes among the Iranian population with low sample size. Patients and methods: In this cross-sectional study, to predict HLA–DQ2 and DQ8 haplotypes, 141(73 male, 78 female) confirmed CD patients compared to 151 healthy controls were enrolled into this study during 2013-2014. HLA DQ2/ DQ8 haplotypes was determined in cases and controls using PCR-SSP technique. Results: DQ2 and DQ8 were positive in 80% (n=111) and 49% (n= 69) of CD patients and 36% (n=61) and 13% (n=21) of control group respectively. Moreover, 32% (n=45) of CD patients and 5.3% (n=8) of the control group were carrier of both haplotypes. In the case group about one-third of patients (32.2%) were positive for carrying both DQ2 and DQ8 heterodimers while only 5.3% (n=8) of the control group were carrier. In addition, the positive likelihood ratio of DQ2 and DQ8 were 1.74 (CI: 1.4- 2.1), and 2.6 (CI: 1.8– 2.7), respectively. Conclusion: The result of this study showed that the frequency of DQ8 among our population is higher than those reported by European countries, but it is close to those founded in South America and Middle East. This result suggests that the higher prevalence of HLA DQ8 pattern in Iranian CD patients is similar to non-European patients. PMID:26744610
Gianfrani, Carmen; Mamone, Gianfranco; la Gatta, Barbara; Camarca, Alessandra; Di Stasio, Luigia; Maurano, Francesco; Picascia, Stefania; Capozzi, Vito; Perna, Giuseppe; Picariello, Gianluca; Di Luccia, Aldo
Microwave based treatment (MWT) of wet wheat kernels induced a striking reduction of gluten, up to <20 ppm as determined by R5-antibodybased ELISA, so that wheat could be labeled as gluten-free. In contrast, analysis of gluten peptides by G12 antibody-based ELISA, mass spectrometry-based proteomics and in vitro assay with T cells of celiac subjects, indicated no difference of antigenicity before and after MWT. SDS-PAGE analysis and Raman spectroscopy demonstrated that MWT simply induced conformational modifications, reducing alcohol solubility of gliadins and altering the access of R5-antibody to the gluten epitopes. Thus, MWT neither destroys gluten nor modifies chemically the toxic epitopes, contradicting the preliminary claims that MWT of wheat kernels detoxifies gluten. This study provides evidence that R5-antibody ELISA alone is not effective to determine gluten in thermally treated wheat products. Gluten epitopes in processed wheat should be monitored using strategies based on combined immunoassays with T cells from celiacs, G12-antibody ELISA after proteolysis and proper molecular characterization.
Cabrera-Chávez, Francisco; Iametti, Stefania; Miriani, Matteo; de la Barca, Ana M Calderón; Mamone, Gianfranco; Bonomi, Francesco
Maize is used as an alternative to wheat to elaborate food stuffs for celiac patients in a gluten-free diet.However, some maize prolamins (zeins) contain amino acid sequences that resemble the wheat gluten immunodominant peptides and their integrity after gastrointestinal proteolysisis unknown. In this study, the celiac IgA-immunoreactivity to zeins from raw or nixtamalized grains, before and after peptic/tryptic digestion was evaluated and their possible immunogenicity was investigated by in silico methods.IgA from some celiac patients with HLA-DQ2 or DQ8 haplotypes recognized two alpha-zeins even after peptic/ tryptic proteolysis. However, digestion affected zeins after denaturation, reduction, and alkylation, used for identification of prolamins as alpha-zein A20 and A30 by MS/MS sequencing. An in silico analysis indicated that other zeins contain similar sequences, or sequences that may bind even better to the HLA-DQ2/DQ8 molecules compared to the already identified ones. Results concur to indicate that relative abundance of these zeins, along with factors affecting their resistance to proteolysis, may be of paramount clinical relevance, and the use of maize in the formulation and preparation of gluten-free foods must be reevaluated in some cases of celiac disease.
Hoffmann, Michelle R; Alzaben, Abeer S; Enns, Simone E; Marcon, Margaret A; Turner, Justine; Mager, Diana R
To identify parental influences affecting micronutrient supplementation in children and adolescents (2-18 years of age) with Celiac Disease (CD), a multi-method (survey, focus groups) study was conducted. A 35-item questionnaire consisting of open- and closed-ended questions was launched nationally via Canadian Celiac Association internet sites. Five focus groups were conducted using a semi-structured interview guide. The survey and semi-structured interview guide content was vetted for face and content validity. Thematic analyses were conducted on the focus group content and open-ended survey questions, and χ(2) and Fischer's exact analysis were performed on closed-ended survey data. Survey respondents were predominantly mothers (97%) of female children (80 F, 49 M) between the ages of 9-12 (31%) with CD, residing in western provinces (55%) with a combined family income ≥$100 000/year (63%). Seventy-seven percent of parental respondent's children or adolescents consumed micronutrient supplements, for 1-5 years (52%), 7 days a week (65%), as both multi-vitamin and single vitamin preparations (40%). Parental influences on child micronutrient use included health beliefs and knowledge, parental supplement use, supplement characteristics, age of child (above or below 13 years), household routines, and provincial residential status (P < 0.05). Parents relied on health professional recommendation (69%; MD, RD) and the internet (21%) as sources of information regarding child micronutrient supplementation. Parental health beliefs and knowledge, socio-demographic factors, and practitioner recommendation influence micronutrient supplement use in children and adolescents with CD.
Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA- DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen- presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association. PMID:8315377
Scorrano, Gabriele; Brilli, Mauro; Martínez-Labarga, Cristina; Giustini, Francesca; Pacciani, Elsa; Chilleri, Filberto; Scaldaferri, Franco; Gasbarrini, Antonio; Gasbarrini, Giovanni; Rickards, Olga
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.
Denecke, Timm; Andreou, Andreas; Podrabsky, Petr; Grieser, Christian; Warnick, Peter; Bahra, Marcus; Klein, Fritz; Hamm, Bernd; Neuhaus, Peter; Glanemann, Matthias
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.
Chowdhury, M K; Chakraborty, R; Gope, S; Rahman, M A; Miah, A R; Raihan, A S; Sarkar, S; Paul, B K; Ferdousi, K R
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.
Rodrigo, Luis; Pérez-Martinez, Isabel
Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD) with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD), having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD. PMID:22481956
Abbasi, Zahra; Nezhad, Seyed Reza Kazemi; Pourmahdi-Broojeni, Mahdi; Rajaei, Elham
Background: Single-nucleotide polymorphism (SNP) rs2476601 within protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) has been shown to be a risk factor for different autoimmune diseases. This study explored the association of 1858 C/T SNP with rheumatoid arthritis (RA) and celiac disease (CD) in a region covering south-west of Iran. Methods: Totally, 52 patients with CD, 120 patients with RA, and 120 healthy subjects were selected. The samples were genotyped for the rs2476601 in PTPN22 gene using the tetra-amplification refractory mutation system polymerase chain reaction. Results: The frequency of +1858T risk allele was significantly increased in both RA (P=0.021, OR=2.56, 95%CI=1.19-5.47) and CD (P=0.002, OR=3.87, 95%CI=1.68-8.95) patients, as compared to the control group. However, no association was found between the +1858C/T PTPN22 gene SNP and the anti-cyclic citrullinated peptide and rheumatoid factor positivity in RA patients. Conclusions: PTPN22 gene could play a crucial role in people’s susceptibility to certain autoimmune diseases. PMID:27215233
Marabotti, Anna; Lepretti, Marilena; Salzano, Anna Maria; Scaloni, Andrea; Vitale, Monica; Zambrano, Nicola; Sblattero, Daniele; Esposito, Carla
Background Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2) activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. Methods and Principal Findings We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins), three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. Conclusions Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here identified in this study
Yuksel, Mahmut; Kaplan, Mustafa; Ates, Ihsan; Kilic, Zeki Mesut Yaln; Kilic, Hasan; Suna, Nuretdin; Ates, Hale; Kayacetin, Ertugrul
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.
Unsal, Oktay; Uzman, Metin; Sapmaz, Ferdane; Dogan, Ozlem Ceylan; Kefeli, Ayse; Asilturk, Zeliha; Yeniova, Abdullah Ozgur; Nazligul, Yasar
Introduction Whether Helicobacter pylori triggers celiac disease (CD) or protects against CD is currently the subject of research. In the literature, there are epidemiologic studies that have reported conflicting results regarding the association between H. pylori and CD. Aim To compare the prevalence of CD autoantibody positivity and the levels of CD autoantibodies between H. pylori-positive and H. pylori-negative subjects. Material and methods This study was prospectively designed and included 240 dyspeptic patients who underwent upper gastrointestinal endoscopy with gastric and duodenal biopsies. The patients were divided into two groups according to presence of H. pylori infection. The serum levels of immunoglobulin (Ig) A, tissue transglutaminase antibodies (tTGA; IgA and IgG classes), and anti-endomysial antibodies (EMA; IgA and IgG classes) were measured for all participants by a blinded biochemistry expert. Results There were no significant differences in the serum levels of CD autoantibodies or IgA between the two groups. There were also no significant differences in the percentages of subjects with positive CD serologies or subjects with IgA deficiencies between the groups. Conclusions Helicobacter pylori remains one of the bacterial species that is most likely to trigger autoimmunity. However, studies have failed to reveal a relationship between H. pylori and CD; thus, additional basic work on the immunological aspects of the microbial-host interactions and longitudinal studies enrolling patients at very early stages of the disease may help us to address this issue. PMID:28337237
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
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
Fagundes-Neto, U; Stump, M V; Wehba, J
The rhythm of nutritional recovery in 11 children with celiac disease after the introduction of a gluten-free diet was studied. The mean age of the patients at the moment of the diagnosis was 2.8 +/- 1.2 years and they were followed up for a period of 3.4 +/- 1.9 years. The nutritional status was evaluated by the utilization of the following parameters: the weight-for-age, height-for-age and weight-for-height. It was verified that none child was well nourished at the moment of the diagnosis and during the evolution 9 of them reached a complete recovery of their nutritional status for the weight in a mean period of time of 5.8 +/- 2.7 months; 5 of these children remained well nourished during the follow-up, 3 for 33 months and 1 for just a month. The other 2 children were initially classified as PCM II and turned to PCM I. The height-for-age index revealed that only 6 children had recovered from malnutrition and only 4 remained like this during all the follow-up. The other 2 children suffered nutritional aggravation and turned to be PCM I, but after a mean time of 18.4 months both resumed the rhythm of growth. Nutritional dwarfsism in 45.45% and chronic evoluted malnutrition in 54.55% were the patterns of malnutrition observed in this group of patients.
DeMelo, Emilia N; McDonald, Charlotte; Saibil, Fred; Marcon, Margaret A; Mahmud, Farid H
The association between celiac disease (CD), an autoimmune condition involving intestinal inflammation related to gluten ingestion, and type 1 diabetes has long been recognized. CD prevalence rates 4 to 6 times greater in adults with type 1 diabetes than in the general population. Much of the existing literature focuses on important implications related to the impact of a gluten-free diet on short-term outcomes in metabolic control and quality of life. Canadian Diabetes Association guidelines recommend targeted CD screening in patients with type 1 diabetes who have classic symptoms, such as abdominal pain, bloating, diarrhea, unexplained weight loss or labile metabolic control; however, a significant proportion (40% to 60%) of patients may have mild or absent symptoms. Recent evidence suggests that adult patients with both conditions are at higher risk for diabetes microvascular comorbidities, increased mortality and impaired bone health if the CD is untreated. The purpose of this review is to describe the association between CD and type 1 diabetes and to summarize recent literature that evaluates risks in patients with both conditions.
Opri, R; Veneri, D; Mengoli, C; Zanoni, G
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 ef