Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, ...tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved.
A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence-based recommendations on CD-specific antibody testing.
In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti-tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA-DQ2 and HLA-DQ8 testing is valuable because CD is unlikely if both haplotypes are negative.
The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.
Coeliac disease and gluten sensitivity Troncone, R.; Jabri, B.
Journal of internal medicine,
June 2011, Letnik:
269, Številka:
6
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
. Troncone R, Jabri B (University Federico II, Naples, Italy; University of Chicago, Chicago, IL, USA). Coeliac disease and gluten sensitivity (Symposium). J Intern Med 2011; 269: 582–590.
Coeliac ...disease (CD) is a systemic immune‐mediated disorder elicited by gluten in genetically susceptible individuals. The common factor for all patients with CD is the presence of a variable combination of gluten‐dependent clinical manifestations, specific autoantibodies (anti‐tissue transglutaminase/anti‐endomysium), HLA‐DQ2 and/or DQ8 haplotypes and different degrees of enteropathy. Recently, gluten sensitivity has received much interest, although the limits and possible overlap between gluten sensitivity and CD remain poorly defined. At present, a number of morphological, functional and immunological disorders that are lacking one or more of the key CD criteria (enteropathy, associated HLA haplotypes and presence of anti‐transglutaminase two antibodies) but respond to gluten exclusion are included under the umbrella of gluten sensitivity. The possible immunological mechanisms underlying these conditions are discussed. Emphasis is given to specific autoantibodies as markers of the coeliac spectrum and to the hypothesis that innate epithelial stress can exist independently from adaptive intestinal immunity in gluten sensitivity.
Since the late 1970s glycine has been considered an important inhibitory neurotransmitter in brain stem and medulla. The description of its involvement in the mechanism of action of the potent ...neurotoxin strychnine pushed further the concept of inhibitory transmitter. The significant concentrations of glycine in forebrain motivated investigators to evaluate different aspects of glycinergic transmission under the ontogenetic, physiologic and pathologic standpoints. This review encompasses a few of these aspects as the role of the different glycine receptors (GlyRs) in intracellular chloride balance, glycine transporters, GABA/Glycine co-release, glycine/NMDA receptor interaction, glycine receptors in acute alcohol effects and advocates a more relevant role for glycine as a stimulatory transmitter in forebrain areas. Finally, the possible co-release of glycine and GABA is considered as an important process to understand the role of glycine in forebrain neural transmission.
Summary
Background
New evidence emerged on early feeding practices and the risk of coeliac disease.
Aim
To systematically update evidence on these practices to find out whether there is a need to ...revise current recommendations.
Methods
MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease‐related autoimmunity.
Results
We identified 21 publications, including two, new, large, randomised controlled trials performed in high‐risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development.
Conclusions
Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.
Celiac disease (CeD) is a multifactorial disease influenced by both genetic and environmental risk factors. CeD genetic components are mainly due to HLA class II genes, which account for ...approximately 40% of the disease heritability. The environmental factor is linked to gliadin ingestion. Despite genetic and epigenetic studies, the pathological molecular mechanism remains unclarified. The strong genetic component does not explain more than half of the hereditability; we identified several epigenetic features that contribute to the understanding of the missing hereditability. The lipid profile of infants has been proposed as a potential biomarker of CeD metabolism that can be measured before they exhibit developmental disorders and clinical symptoms. We suggest that the state of the host is a main factor for the abnormal immune response to gluten. Long before any exposure to the offending agent or any production of specific antibodies, several molecular mechanisms are differentially expressed in infants who will develop CeD compared to their peers matched for the same genetic profile. The present study explored the serum phospholipid profile of a group of infants at risk for celiac disease, followed up to 8 years to monitor the onset of CeD. We compared 30 patients who developed the disease with 20 age- and sex-matched peers with similar genetic profiles who did not develop the disease within 8 years. Serum phospholipids were analysed at 4 months, before exposure to gluten, and at 12 months of age, when none showed any marker of disease. In the 30 CeD patients, we also analysed the serum at the time of diagnosis (>24 months). The serum phospholipid profile was fairly constant across 4 and 12 months of age and, in CeD, up to 24-36 months. The phospholipid signature was dramatically different in infants who developed CeD when compared to that of control NY-CeD (Not Yet developing Celiac Disease) peers. We identified a specific serum phospholipid signature that predicts the onset of celiac disease in HLA at-risk infants years before the appearance of antibodies specific for CeD in the serum and before any clinical symptoms, even before gluten introduction into the diet at 4 months. Specifically, lysophosphatidylcholine, phosphatidylcholine, alkylacyl-phosphatidylcholine, phosphoethanolamines, phosphatidylserines, phosphatidylglycerol and phosphatidylinositol were found to be differentially represented in CeD versus NY-CeD. A set constituted by a limited number of alkylacyl-phosphatidylcholine and lyso-phosphatidylcholine, together with the duration of breast-feeding, allows the discrimination of infants who develop celiac disease before 8 years of age from those at a similar genetic risk who do not develop the disease. In addition to recent discovery, our paper unveiled a specifc phopholipid profile, able to discriminate infants who eventually develop celiac disease years before antibodies or clinical symptoms ensue.
Summary
Background
A gluten‐free diet is currently the only reliable therapeutic strategy that is approved for coeliac disease (CD). For many patients, however, compliance remains inadequate.
Aim
To ...investigate the immunogenicity of wheat flour that was pre‐treated with selected lactobacilli and fungal proteases (hydrolysed wheat gluten) in coeliac patients.
Methods
The immunogenicity of hydrolysed wheat gluten was evaluated both in vitro in intestinal T cell lines (TCLs) and in vivo in treated CD patients after a short‐term gluten challenge. Twenty treated CD patients were enrolled and equally randomised into two groups. The patients ate bread that was prepared with hydrolysed wheat flour or natural wheat flour (10 g of gluten/d for 3 days). The interferon (INF)‐γ responses to natural gliadin and a 33‐mer peptide were assessed by the enzyme‐linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) both before and 6 days after the start of the challenge.
Results
Hydrolysed wheat was not able to activate the TCLs from the coeliac intestinal mucosa. Consistent with the in vitro results, no significant increase in INF‐γ secretion was observed in patients who consumed hydrolysed wheat flour. Conversely, the consumption of natural wheat gluten mobilised INF‐γ secreting cells in the blood (P<.05).
Conclusions
We confirm that fermentation of wheat flour with sourdough lactobacilli and fungal proteases is capable of abolishing the T cell immunogenicity of gluten in coeliac patients. Our data also validate the short‐term oral challenge as a useful tool for testing the efficacy of novel therapeutic approaches.
Summary
Background
PREVENTCD, Prevent Coeliac Disease, is an international project investigating the hypothesis of possible induction of tolerance to gluten in genetically predisposed children ...through introducing small quantities of gluten during the period of breastfeeding.
Aim
To summarise current knowledge on the possible relationship between early feeding practices and the risk of coeliac disease (CD).
Methods
The Cochrane Library, MEDLINE, and EMBASE databases were searched in May 2011, and the search was updated in January 2012, and again in July 2012.
Results
Breastfeeding (BF) and CD: some studies show a protective effect of BF, while others show no effect. No studies have shown a long‐term preventive effect. BF at the time of gluten introduction and CD: Results from a meta‐analysis of five observational case‐control studies suggest that BF at gluten introduction is associated with a lower risk of CD compared with formula feeding. It is unclear whether BF provides a permanent protection or only delays the onset of CD. Timing of gluten introduction: The data suggest that both early (≤4 months) and late (≥7 months) introduction of gluten may increase the risk of CD. Amount of gluten at weaning (and later) and CD: One incident case‐referent study documented that the introduction of gluten in large amounts compared with small or medium amounts increased the risk of CD.
Conclusions
In the absence of clear evidence, in order to decrease the risk of later coeliac disease, it is reasonable to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten while the infant is still being breastfed. Future studies may clarify the remaining uncertainties.
Butyrate acts as energy source for intestinal epithelial cells and as key mediator of several immune processes, modulating gene expression mainly through histone deacetylation inhibition. Thanks to ...these effects, butyrate has been proposed for the treatment of many intestinal diseases. Aim of this study was to investigate the effect of butyrate on the expression of a large series of target genes encoding proteins involved in pro-inflammatory pathways. We performed quantitative real-time-PCR analysis of the expression of 86 genes encoding proteins bearing to pro-inflammatory pathways, before and after butyrate exposure, in primary epithelial cells derived from human small intestine and colon. Butyrate significantly down-regulated the expression of genes involved in inflammatory response, among which nuclear factor kappa beta, interferon-gamma, Toll like 2 receptor and tumour necrosis factor-alpha. Further confirmations of these data, including studies at protein level, would support the use of butyrate as effective therapeutic strategy in intestinal inflammatory disorders.
Coeliac disease (CD) is a very common food‐sensitive enteropathy, which is triggered by gluten ingestion and is mediated by CD4+ T cells. In addition, alterations in the intestinal microbiota that is ...normally involved in the homeostasis of GALT (gut‐associated lymphoid tissue) seem to play a role in CD. In accordance with these findings, we previously reported that Lactobacillus casei can induce a strong enhancement of the T cell‐mediated response to gliadin without inducing enteropathy. In this study, we analysed the effects of L. casei administration in a mouse model of gliadin‐induced villous damage that was recently developed and involves the inhibition of cyclo‐oxygenase (COX) activities in gliadin‐sensitized HLA‐DQ8 transgenic mice. To address the issue, we assessed the weight loss, the intestinal cytokine pattern, the density of CD25+ cells and morphometry of the gut mucosa. We confirmed that COX inhibition in sensitized mice caused villus blunting, dysregulated expression of tumour necrosis factor (TNF)‐α and reduced gliadin‐specific IL‐2 production. Notably, the administration of probiotic strain induced a complete recovery of villus blunting. This finding was associated with a delay in weight decrease and a recovery of basal TNF‐α levels, whereas the numbers of CD25+ cells and the levels of IL‐2 remained unchanged. In conclusion, our data suggest that the administration of L. casei can be effective in rescuing the normal mucosal architecture and GALT homeostasis in a mouse model of gliadin‐induced enteropathy.
Summary
In coeliac disease (CD), anti‐tissue transglutaminase 2 immunoglobulin (Ig)A antibodies (anti‐TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European ...multi‐centre study, which investigates the influence of infant nutrition and that of genetic, immunological and other environmental factors on the risk of developing CD. The aim of the current study was to evaluate the appearance of intestinal anti‐TG2 deposits in very early intestinal biopsies from at‐risk infants and their predictive value for villous atrophy. Sixty‐five small bowel biopsies, performed in 62 children, were investigated for the presence of intestinal anti‐TG2 extracellular IgA deposits by using double immunofluorescence. The biopsies were performed in the presence of elevated serum levels of CD‐associated antibodies and/or symptoms suggesting disease. Deposits of anti‐TG2 IgA were present in 53 of 53 CD patients and three of three potential CD patients. In potential CD patients, mucosal deposits showed a patchy distribution characterized by some areas completely negative, whereas active CD patients had uniformly present and evident mucosal deposits. Only one of six patients without CD (negative for serum anti‐TG2 and with normal mucosa) had intestinal deposits with a patchy distribution and a weak staining. Two of the 53 CD patients received a definitive diagnosis of CD after a second or third biopsy; mucosal deposits of anti‐TG2 IgA were evaluated in all samples. Before developing villous atrophy, both patients had anti‐TG2 deposits in normal mucosal architecture, antibodies in one patient being absent in serum. We demonstrated that in CD the intestinal deposits of anti‐TG2 are a constant presence and appear very early in the natural history of disease.
In Coeliac Disease anti‐tissue transglutaminase2 IgA antibodies (anti‐TG2) are produced and deposited in the intestine. In our study, we aimed to investigate in very early intestinal biopsies from children at risk for Celiac Disease their appearance and their predictive value for villous atrophy.
We demonstrated that in Celiac Disease the intestinal deposits of anti‐TG2 are constant presence.
They appear very early in the natural history of disease.
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