Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children: validation study

Objective To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms.Setting Tertiary care children's hospital.Participants Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls. Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet.Main outcome measures Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples, determined in duplicate by using recommended cut-off limits.Results Sensitivity of faecal antibodies against human tissue transglutaminase was 10% (95% confidence interval 1% to 32%), and specificity was 98% (91% to 100%). For antibodies against gliadin, sensitivity was 6% (0% to 29%) and specificity was 97% (89% to 100%). Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82%, but specificity decreased to 58%. All follow-up stool tests remained negative, except for two positive anti-gliadin results in one patient, six and 10 weeks after the gluten-free diet was started.Conclusions Neither stool test was suitable for screening for coeliac disease in children with symptoms

Celiac disease

Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for clinically overt celiac disease varies from 1:270 in Finland to 1:5000 in North America. Since celiac disease can be asymptomatic, most subjects are not diagnosed or they can present with atypical symptoms. Furthermore, severe inflammation of the small bowel can be present without any gastrointestinal symptoms. The diagnosis should be made early since celiac disease causes growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms. Diagnosis requires endoscopy with jejunal biopsy. In addition, tissue-transglutaminase antibodies are important to confirm the diagnosis since there are other diseases which can mimic celiac disease. The exact cause of celiac disease is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen); often the disease is inherited. Management consists in life long withdrawal of dietary gluten, which leads to significant clinical and histological improvement. However, complete normalization of histology can take years

Intestinal Barrier Function in Gluten-Related Disorders

Gluten-related disorders include distinct disease entities, namely celiac disease, wheat-associated allergy and non-celiac gluten/wheat sensitivity. Despite having in common the contact of the gastrointestinal mucosa with components of wheat and other cereals as a causative factor, these clinical entities have distinct pathophysiological pathways. In celiac disease, a T-cell mediate immune reaction triggered by gluten ingestion is central in the pathogenesis of the enteropathy, while wheat allergy develops as a rapid immunoglobulin E- or non-immunoglobulin E-mediated immune response. In non-celiac wheat sensitivity, classical adaptive immune responses are not involved. Instead, recent research has revealed that an innate immune response to a yet-to-be-defined antigen, as well as the gut microbiota, are pivotal in the development in this disorder. Although impairment of the epithelial barrier has been described in all three clinical conditions, its role as a potential pathogenetic co-factor, specifically in celiac disease and non-celiac wheat sensitivity, is still a matter of investigation. This article gives a short overview of the mucosal barrier of the small intestine, summarizes the aspects of barrier dysfunction observed in all three gluten-related disorders and reviews literature data in favor of a primary involvement of the epithelial barrier in the development of celiac disease and non-celiac wheat sensitivity

Gluten Immunogenic Peptides as Standard for the Evaluation of Potential Harmful Prolamin Content in Food and Human Specimen

Gluten is a complex mixture of storage proteins in cereals like wheat, barley, and rye. Prolamins are the main components of gluten. Their high content in proline and glutamine makes them water-insoluble and difficult to digest in the gastrointestinal tract. Partial digestion generates peptide sequences which trigger immune responses in celiac and gluten-sensitive patients. Gluten detection in food is challenging because of the diversity, in various food matrices, of protein proportions or modifications and the huge number of immunogenic sequences with differential potential immunoactivity. Attempts to develop standard reference materials have been unsuccessful. Recent studies have reported the detection of a limited number of dominant Gluten Immunogenic Peptides (GIP) that share similarities to epitopes presented in the α-gliadin 33-mer, which showed to be highly proteolytic resistant and is considered to be the most immunodominant peptide within gluten in celiac disease (CD). GIP were detectable and quantifiable in very different kind of difficult to analyze food, revealing the potential immunogenicity by detecting T-cell activity of celiac patients. But GIP were also found in stool and urine of celiac patients on a supposedly gluten-free diet (GFD), showing the capacity to resist and be absorbed and excreted from the body, providing the first simple and objective means to assess adherence to the GFD. Methods to specifically and sensitively detect the most active GIP in food and biological fluids are rational candidates may use similar analytical standard references for determination of the immunopathological risk of gluten exposure in gluten-related diseases.España, MINECO AGL2013-48946-CEspaña, Ministerio de Ciencia, Innovación y Universidades y Corporación Tecnológica de Andalucía (CTA

Bread and other edible agents of mental disease

Perhaps because gastroenterology, immunology, toxicology, and the nutrition and agricultural sciences are outside of their competence and responsibility, psychologists and psychiatrists typically fail to appreciate the impact that food can have on their patients’ condition. Here we attempt to help correct this situation by reviewing, in non-technical, plain English, how cereal grains—the world’s most abundant food source—can affect human behavior and mental health. We present the implications for the psychological sciences of the findings that, in all of us, bread (1) makes the gut more permeable and can thus encourage the migration of food particles to sites where they are not expected, prompting the immune system to attack both these particles and brain-relevant substances that resemble them, and (2) releases opioid-like compounds, capable of causing mental derangement if they make it to the brain. A grain-free diet, although difficult to maintain (especially for those that need it the most), could improve the mental health of many and be a complete cure for others

The Dietary Intervention of Transgenic Low-Gliadin Wheat Bread in Patients with Non-Celiac Gluten Sensitivity (NCGS) Showed No Differences with Gluten Free Diet (GFD) but Provides Better Gut Microbiota Profile

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.España, MINECO Projects AGL2013-48946-C3-1-R, AGL2013-48946-C and AGL2016-80566-

Coeliac disease: where are we in 2014?

Presents up-to-date information on coeliac disease, with recommendations on whom to test and how to test them, and how to manage patients once they are diagnosed. Summary Background Coeliac disease (CD) is an autoimmune condition affecting at least 1% of the population, many of whom remain undiagnosed. It is characterised by chronic inflammation of the small-intestinal mucosa and triggered by eating gluten. It is challenging to diagnose because of the many and varied ways in which it may present. Discussion Primary care practitioners have a crucial role in improving rates of CD diagnosis, and in the ongoing care of patients with CD. A blood test for coeliac-specific antibodies will identify most patients who need to undergo duodenal biopsy to make the diagnosis. Management encompasses supporting patients with adherence to the gluten-free diet and conducting a CD-focused clinical review every 1–2 years

Coeliac crisis with severe hypokalaemia in an adult

Coeliac crisis is a rare life-threatening presentation of coeliac disease, in which acute dramatic metabolic derangements are present. It is observed mainly in children less than two years of age. In adults, coeliac disease usually has an indolent course and presents with mild gastrointestinal symptoms or may even be asymptomatic and present with long term complications including anaemia, osteoporosis and infertility. This case describes a 38 year old gentleman who presented with acute diarrhoea that led rapidly to severe metabolic disturbances including life threatening hypokalaemia. This case illustrates the heterogeneous clinical course of coeliac disease and the importance of considering it in the differential diagnosis of adult patients presenting with acute diarrhoea and metabolic disturbances.peer-reviewe