A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants.

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.

Intestinal anti-transglutaminase 2 immunoglobulin A deposits in children at risk for coeliac disease (CD): data from the PreventCD study.

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.

Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells.

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.

Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short-term oral challenge.

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.

Systematic review with meta-analysis: early infant feeding and coeliac disease--update 2015.

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.

Intestinal titres of anti-tissue transglutaminase 2 antibodies correlate positively with mucosal damage degree and inversely with gluten-free diet duration in coeliac disease.

It has always been known that anti-tissue transglutaminase 2 (anti-TG2) antibodies are produced in the small intestine. Their serum titres correlate with mucosal damage degree and decrease on a gluten-free diet (GFD). We aimed to correlate intestinal anti-TG2 antibodies levels with degree of mucosal damage and GFD duration. Thirty-four active, 71 potential and 24 CD patients on GFD for at least 2 years were enrolled. Anti-TG2 deposits were detected in intestinal biopsies by double immunofluorescence. Biopsies were cultured for 24 h with medium, and with gliadin peptic tryptic digest (PTG) or A-gliadin peptide 31-43 (P31-43). Anti-TG2 antibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay (ELISA). All active CD patients secreted high titres of anti-TG2 antibodies into culture medium that increased with the worsening of mucosal injury (Spearman's r = 0·71; P < 0·0001). Seventy of 71 potential CD patients and 15 of 24 treated CD patients secreted low titres of anti-TG2 antibodies into supernatants, eight of nine negative treated patients being on GFD for more than 10 years. An inverse correlation between antibody titres and duration of GFD was found, (Spearman's r = -0·52; P < 0·01). All active, 53 of 71 potential and six of 24 treated, CD patients showed anti-TG2 mucosal deposits. Five of six positive treated CD patients had been on GFD for fewer than 6 years and were also positive for secreted anti-TG2. In treated patients, PTG/P31-43 was not able to induce secretion of anti-TG2 antibodies into culture medium. Measurement of anti-TG2 antibodies in biopsy supernatants proved to be more sensitive than detection by immunofluorescence to reveal their intestinal production. Intestinal antiTG2 antibodies titres correlated positively with the degree of mucosal damage and inversely with the duration of GFD.

Atopy patch tests are useful to predict oral tolerance in children with gastrointestinal symptoms related to non-IgE-mediated cow's milk allergy.

Atopy patch tests (APTs) have been proposed for the diagnostic approach in children with non-IgE-mediated cow's milk allergy and gastrointestinal symptoms. We aimed to investigate the benefit of APTs in predicting oral tolerance in these patients. We prospectively evaluated 172 subjects with a sure diagnosis of non-IgE-mediated CMA and gastrointestinal symptoms (97 boys, 56.4%; age, 6.37 m; range, 2-12 m). At diagnosis, 113/172 (65.7%) children had positive APTs to cow's milk proteins (CMP). After 12 months of exclusion, diet APTs were repeated immediately before OFC. APTs significantly correlated (P < 0.001) with the OFC outcome (r 0.579). Diagnostic accuracy was sensitivity of 67.95%, specificity of 88.3%, PPV of 82.81%, NPV of 76.85%, and a +LR of 5.80. APTs are a valuable tool in the follow-up of children with non-IgE-mediated CMA-related gastrointestinal symptoms by contributing in determining whether an OFC can safely be undertaken.

Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease.

Anti-tissue transglutaminase 2 (anti-TG2) antibodies are present in the serum of the great majority of untreated coeliac disease (CD) patients. They are produced and deposited in the small intestinal mucosa. Potential CD patients present serum anti-TG2 antibodies higher than cut-off, but a normal duodenal mucosa where mucosal deposits of anti-TG2 are not always detectable. The aim of our work was to investigate the presence of anti-TG2 intestinal antibodies in patients with potential CD, and identify the most sensitive test to detect them. Twelve active CD patients, 28 potential CD patients and 39 non-CD controls were enrolled. Biopsy fragments from all patients were analysed by double immunofluorescence to detect mucosal deposits of anti-TG2 antibodies. Fragments from the same subjects were also cultured for 24 h with medium in the presence or absence of gliadin peptides. Anti-TG2 autoantibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay. All active CD, 68% of potential CD patients and 20% of non-CD controls showed mucosal deposits of immunoglobulin (Ig)A anti-TG2; at the same time 100, 96 and 8% of active CD, potential CD and non-CD control patients secreted these antibodies in culture supernatants, respectively. Our data showed that, to detect intestinal anti-TG2 antibodies, the measurement of antibodies secreted into culture supernatants has higher sensitivity and specificity (97·5 and 92·3%, respectively) than the detection of mucosal deposits (77·5 and 80·0%, respectively). The measurement of intestinal anti-TG2 antibodies may prove useful in clinical practice to predict evolution towards mucosal atrophy in potential coeliac patients and identify patients with gluten sensitivity.

Systematic review: early infant feeding and the prevention of coeliac disease.

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.

Short wheat challenge is a reproducible in-vivo assay to detect immune response to gluten.

It has been reported that interferon (IFN)-γ-secreting T cells reactive to gluten can be detected in the peripheral blood of individuals with treated coeliac disease (CD) after a short consumption of wheat-containing food. By contrast, very little is known about the reproducibility of this in-vivo procedure in the same patient cohort which underwent two, or more, gluten consumptions. Fourteen coeliac patients in remission consumed wheat bread for 3 days; 13 underwent a second gluten challenge after a wash-out of 3-10 months on a strict gluten-free diet. Immune reactivity to gluten was analysed in peripheral blood by detecting IFN-γ before and 6 days after commencing a gluten diet. Gliadin-specific IFN-γ-secreting CD4(+) T cells increased significantly on day 6 of the first challenge. These cells resulted as prevalently human leucocyte antigen (HLA)-DQ restricted and with a phenotype of gut homing, as suggested by the expression of ß7-integrin. Similarly, reactiveness to gliadin was observed after the second wheat consumption, although with an individual variability of responses at each challenge. Our findings confirmed that the short wheat challenge is a non-invasive approach to investigate the gluten-related immune response in peripheral blood of subjects intolerant to gluten. Furthermore, we demonstrated that the in-vivo procedure can be reproduced in the same subject cohort after a gluten wash-out of at least 3 months. Our study has important implications for the application of this procedure to clinical practice.

Coeliac disease diagnosis: ESPGHAN 1990 criteria or need for a change? Results of a questionnaire.

BACKGROUND AND OBJECTIVES: A revision of criteria for diagnosing coeliac disease (CD) is being conducted by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). In parallel, we have performed a survey aimed to evaluate present practices for CD among paediatric gastroenterologists and to learn their views on the need for modification of present criteria for CD diagnosis. PATIENTS AND METHODS: Questionnaires were distributed to experienced paediatric gastroenterologists (ESPGHAN members) via the Internet. RESULTS: Overall, 95 valid questionnaires were available for analysis, pertaining to 28 different countries, with the majority of responders treating patients with CD for >15 years. Only about 12% of the responders comply with present criteria, noncompliance being related mainly to the challenge policy. Approximately 90% request a revision and modification of the present criteria. Forty-four percent want to omit the small bowel biopsy in symptomatic children with positive anti-tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies, especially if they are DQ2/DQ8 positive. For silent cases detected by screening with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30% consider that no small bowel biopsy should be required in selected cases. Adding human leukocyte antigen typing in the diagnostic workup was asked for by 42% of the responders. As for gluten challenge, a new policy is advocated restricting its obligation to cases whenever the diagnosis is doubtful or unclear. CONCLUSIONS: Based on these opinions, revision of the ESPGHAN criteria for diagnosing CD is urgently needed.

European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Immunomodulatory effects of Lactobacillus casei administration in a mouse model of gliadin-sensitive enteropathy.

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.

Coeliac disease and gluten sensitivity.

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.

High density of intraepithelial gammadelta lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency.

The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)gammadelta(+) intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRgammadelta(+) IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRgammadelta(+) IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRgammadelta(+) IELs than controls (P < 0.05), but lower than IgAD with CD (P < 0.01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCRgammadelta(+)/CD3+ ratio than the control group (P < 0.05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD, one of seven with potential CD and none of those without CD. Most of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti-TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and immunohistochemical markers do not discriminate between IgAD and potential CD with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very important for the diagnosis of CD in IgAD.

Prevalence of atopy in children with chronic constipation.

OBJECTIVES: To evaluate the prevalence of chronic constipation (CC) in unselected children, its association with atopy and the efficacy of a cow's milk protein (CMP) elimination diet on refractory constipation. STUDY DESIGN: The study was conducted by six primary care paediatricians, serving a population of 5113 children aged from birth through to 12 years; only 2068 children were 6 months to 6 years. During a 3-month period, prevalence of CC was determined for the entire study population, ages 0-12 years. In the second part of the study, all patients aged 6 months to 6 years with CC, and age- and sex-matched controls, were evaluated for atopy and its association with CC. A questionnaire was completed including personal and family history of atopy and bowel-movement characteristics. Patients were tested for atopy by specific serum IgE and/or skin-prick tests. Constipated patients, refractory to osmotic laxatives, underwent a 4-week CMP elimination diet. RESULTS: 91 (1.8%) children had CC, and 69 (3.3%) of the 6 months to 6 years age group fell into the atopy study age range. All 69 constipated children (mean age 34.9 (18.0) months) and 69 controls completed the questionnaire. Twelve of the 69 constipated children (17.3%) and 13 out of the 69 control children (18.8%) had a diagnosis of atopy. Eleven out of 69 (15.9%) constipated children were refractory to constipation treatment, and three (27.3%) of these had atopy. The 4-week trial of dietary elimination did not result in improvement in any of these 11 children. CONCLUSIONS: In our study group, prevalence of atopy among children with CC is similar to that in the general population. The level of refraction of CC does not seem to be related to cow's milk allergy.

Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease.

BACKGROUND: An accurate monitoring of mucosal inflammation is important for an effective management of patients with inflammatory bowel disease. Intestinal inflammation can be detected by faecal calprotectin level determination. AIM: To comparatively evaluate the accuracy of faecal calprotectin, clinical scores, common serum markers and endoscopy in the assessment of the severity of intestinal mucosa inflammation in children with inflammatory bowel disease. METHODS: Fifty-eight paediatric patients (mean age 13.9 years, 95% CI 2.9-14.8; male 28) with confirmed inflammatory bowel disease (26 Crohn's disease, 32 ulcerative colitis) were enrolled. Before endoscopy, all patients underwent a complete evaluation including: clinical scores, erythrocyte sedimentation rate, C-reactive protein and faecal calprotectin determination. The severity of mucosal inflammation was assessed using specific endoscopic and histologic scores. RESULTS: Faecal calprotectin showed a high correlation (r=0.655) with the histologic grade of mucosal inflammation, similar to that observed for endoscopy (r=0.699), and it resulted the most accurate tool (sensitivity 94%, specificity 64%, positive predictive value 81%, negative predictive value 87%) to detect the presence of active mucosal inflammation when compared to clinical scores and common serum markers. In patients with apparent clinical and laboratory remission the accuracy of faecal calprotectin resulted further improved (sensitivity 100%, specificity 80%, positive predictive value 67%, negative predictive value 100%). CONCLUSIONS: A more accurate assessment of the severity of mucosal inflammation can be achieved by the determination of faecal calprotectin levels compared to other common clinical and laboratory indices. This non-invasive and objective method could be particular useful in patients with apparent clinical and laboratory remission.

Review article: future research on coeliac disease - a position report from the European multistakeholder platform on coeliac disease (CDEUSSA).

BACKGROUND: CDEUSSA is a Specific Support Action project from the Sixth Framework Programme Priority of the European Union (EU). Its aim is to bring together basic and applied research in the area of coeliac disease (CD). This paper reviews the main issues that are a result of the CDEUSSA initiative. AIM: To identify the major issues in need of investigation in the areas of clinical aspects, treatment, prevention and public health. METHODS: Key stakeholders, representing a wide range of knowledge with crucial importance for CD research and practice, have participated in two workshops aimed at identifying and proposing to the EU, as high priority research, topics in the areas of clinical aspects, treatment, prevention and public health. RESULTS: In public health, the overall goal should be to improve quality of life of the European population by implementing primary prevention strategies, early diagnosis and improved treatments for CD. New treatment strategies need to be developed. The option of primary prevention should be fully explored, which requires combined epidemiological, clinical and basic scientific research efforts. Such studies should also consider the importance of gene-environment interactions in the development of CD. Increased knowledge is needed on the natural history of CD. Diagnostic criteria need to be revised. CONCLUSIONS: To achieve these goals, a collaboration of the stakeholders is fundamental, including research and patient organizations, as well as industries within both diagnostics and food production.