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

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.

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Erythema Nodosum in a Child with Celiac Disease

Case Reports in Pediatrics ◽

10.1155/2011/935153 ◽

2011 ◽

Vol 2011 ◽

pp. 1-2 ◽

Cited By ~ 1

Author(s):

Andrew Fretzayas ◽

Maria Moustaki ◽

Olga Liapi ◽

Polyxeni Nicolaidou

Keyword(s):

Celiac Disease ◽

Histological Examination ◽

Erythema Nodosum ◽

Gluten Free Diet ◽

Systemic Diseases ◽

Gluten Free ◽

Serological Tests ◽

Extraintestinal Manifestation ◽

Common Causes

Erythema nodosum is an acute, nodular, erythematous eruption usually limited to the extensor aspects of the lower legs. It could be idiopathic or associated with other systemic diseases. We, herein, report a phenotypically healthy, ten-year-old boy who presented with erythema nodosum in whom serological tests of autoimmunity and intestinal histological examination were compatible with celiac disease. The eruption resolved within 2 months following a gluten-free diet. Therefore, the possibility that erythema nodosum represents an extraintestinal manifestation of celiac disease should be kept in mind accordingly in cases where other common causes of this rash are ruled out.

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Novel Treatments for Celiac Disease: Glutenases and Beyond

Digestive Diseases ◽

10.1159/000369536 ◽

2015 ◽

Vol 33 (2) ◽

pp. 277-281 ◽

Cited By ~ 13

Author(s):

Katri Kaukinen ◽

Katri Lindfors

Keyword(s):

Celiac Disease ◽

Dietary Treatment ◽

Gluten Free Diet ◽

Intestinal Lumen ◽

Gluten Free ◽

Novel Treatments ◽

Gluten Peptides ◽

Downstream Effects ◽

Complete Digestion ◽

Novel Drug

Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet. However, gluten-free dieting is restrictive, difficult to maintain and nutritionally less than optimal. The improved knowledge on celiac disease pathogenesis has enabled researchers to suggest alternative strategies to treat the disorder. The drug development poses a challenge as any novel drug for celiac disease should be simultaneously effective and as safe as the gluten-free diet. The rationale behind enzyme supplementation therapy as a future treatment option for celiac patients lies in the fact that gluten is only poorly digested by gastrointestinal proteases. Due to incomplete degradation in the gastrointestinal tract, fairly long gluten peptides enter the small-intestinal lumen and come into contact with the mucosal epithelium, and in celiac disease patients this encounter launches deleterious downstream effects. Enzyme supplement therapy using either bacterial or fungal endopeptidases or proteases from germinating cereals has been proposed to promote complete digestion of prolamins and destroy disease-inducing gluten peptides. A major advantage of these glutenases is that they work in the lumen of the small intestine and do not themselves take part in the immunological cascade of events in the lamina propria, thus being unlikely to cause harmful side effects to the host. Studies to test this rationale, e.g. with Aspergillus niger prolyl endoprotease and a combination enzyme product ALV003, are already ongoing. The development of a novel medication for celiac disease is still in its early days, and thus the conventional dietary treatment will hold its place for the time being.

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Gluten Degrading Enzymes for Treatment of Celiac Disease

Nutrients ◽

10.3390/nu12072095 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2095 ◽

Cited By ~ 4

Author(s):

Guoxian Wei ◽

Eva J. Helmerhorst ◽

Ghassan Darwish ◽

Gabriel Blumenkranz ◽

Detlef Schuppan

Keyword(s):

Celiac Disease ◽

Enzyme Stability ◽

Clinical Manifestations ◽

Cysteine Proteases ◽

Gluten Free Diet ◽

Gluten Free ◽

Strict Adherence ◽

Degrading Enzymes ◽

Gluten Peptides ◽

Promising Therapeutic Approach

Celiac disease (CeD) affects about 1% of most world populations. It presents a wide spectrum of clinical manifestations, ranging from minor symptoms to mild or severe malabsorption, and it may be associated with a wide variety of autoimmune diseases. CeD is triggered and maintained by the ingestion of gluten proteins from wheat and related grains. Gluten peptides that resist gastrointestinal digestion are antigenically presented to gluten specific T cells in the intestinal mucosa via HLA-DQ2 or HLA-DQ8, the necessary genetic predisposition for CeD. To date, there is no effective or approved treatment for CeD other than a strict adherence to a gluten-free diet, which is difficult to maintain in professional or social environments. Moreover, many patients with CeD have active disease despite diet adherence due to a high sensitivity to traces of gluten. Therefore, safe pharmacological treatments that complement the gluten-free diet are urgently needed. Oral enzyme therapy, employing gluten-degrading enzymes, is a promising therapeutic approach. A prerequisite is that such enzymes are active under gastro-duodenal conditions, quickly neutralize the T cell activating gluten peptides and are safe for human consumption. Several enzymes including prolyl endopeptidases, cysteine proteases and subtilisins can cleave the human digestion-resistant gluten peptides in vitro and in vivo. Examples are several prolyl endopeptidases from bacterial sources, subtilisins from Rothia bacteria that are natural oral colonizers and synthetic enzymes with optimized gluten-degrading activities. Without exception, these enzymes must cleave the otherwise unusual glutamine and proline-rich domains characteristic of antigenic gluten peptides. Moreover, they should be stable and active in both the acidic environment of the stomach and under near neutral pH in the duodenum. This review focuses on those enzymes that have been characterized and evaluated for the treatment of CeD, discussing their origin and activities, their clinical evaluation and challenges for therapeutic application. Novel developments include strategies like enteric coating and genetic modification to increase enzyme stability in the digestive tract.

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Quantitative assessment of nutrition and nutritional status of patients with celiac disease aged 13–18

Roczniki Państwowego Zakładu Higieny ◽

10.32394/rpzh.2019.0084 ◽

2019 ◽

pp. 359-367 ◽

Cited By ~ 2

Keyword(s):

Vitamin D ◽

Celiac Disease ◽

Nutritional Status ◽

Quantitative Assessment ◽

European Population ◽

Gluten Free Diet ◽

Study Group ◽

Gluten Free ◽

Serological Tests ◽

The Right

Background. Celiac disease is an autoimmune disease that affects about 1% of the European population and 0.3–1.3% of the world’s population. The only method of treatment is introduction of a gluten-free diet. Objective. The aim of the study was to assess the nutrition of adolescents with celiac disease and to assess their nutritional status. Materials and methods. The study group comprised 24 patients with diagnosed celiac disease. The diagnosis was based on biopsy, serological tests and, in some cases, genetic tests. Anthropometric measurements included height, which was respectively 161.9 ±12.43 cm in boys and 163.6 ±9.03 cm in girls, and body weight oscillating between 56.55 ±16.24 kg for boys and 52.62 ±10.92 kg for girls. To assess the way of nutrition used an individually prepared questionnaire including an interview from the last 24 h. The menus were analyzed using the Dieta 5d program. The statistical analysis of the data was made using Statistica 12 program. Results. Gluten-free diet contributes to the occurrence of caloric deficiencies up to 36%. It was found inadequate intake of dietary fiber, for girls 15.45 ±9.84 g and 14.41 ±4.73 g for boys. It has been observed too low intake of ingredients such as calcium (565.65 ±347.41 mg), magnesium (223.41 ±73.84 mg), vitamin D (1.34 ±1.28 μg) and E (5.05 ±2.32 mg) as well as potassium (2848.67 ±1132.07 mg), iron (7.62 ±2.05 mg), zinc (7.11 ±2.41 mg) and thiamine (0.87 ±0.38 mg). The ingredients such as riboflavin, niacin, pyridoxine, cobalamin, and vitamins C and A were consumed in the right amount. Conclusions. Incorrectly used gluten-free diet may contribute to the recurrence of the disease. Chronic inadequate intake of fiber can lead to constipation. A deficiency of many nutrients can result in impaired development of the young organism such as anemia, growth retardation or osteoporosis.

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