Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86 .

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.

Background: Enteropathy in coeliac disease (CD) is sustained by a gliadin specific Th1 response. Interleukin (IL)-10 can downregulate Th1 immune responses. Aim: We investigated the ability of recombinant human (rh) IL-10 to suppress gliadin induced Th1 response. Patients and methods: IL-10 RNA transcripts were analysed by competitive reverse transcription-polymerase chain reaction in duodenal biopsies from untreated and treated CD patients, non-coeliac enteropathies (NCE), and controls. CD biopsies were cultured with a peptic-tryptic digest of gliadin with or without rhIL-10. The proportion of CD80+ and CD25+ cells in the lamina propria, epithelial expression of Fas, intraepithelial infiltration of CD3+ cells, as well as cytokine synthesis (interferon γ (IFN-γ) and IL-2) were measured. Short term T cell lines (TCLs) obtained from treated CD biopsies cultured with gliadin with or without rhIL-10 were analysed by ELISPOT for gliadin specific production of IFN-γ. Results: In untreated CD and NCE, IL-10 RNA transcripts were significantly upregulated. In ex vivo organ cultures, rhIL-10 downregulated gliadin induced cytokine synthesis, inhibited intraepithelial migration of CD3+ cells, and reduced the proportion of lamina propria CD25+ and CD80+ cells whereas it did not interfere with epithelial Fas expression. In short term TCLs, rhIL-10 abrogated the IFN-γ response to gliadin. Conclusions: rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacity of lamina propria mononuclear cells as it reduces the expression of CD80. Interestingly, rhIL-10 also induces a long term hyporesponsiveness of gliadin specific mucosal T cells. These results offer new perspectives for therapeutic strategies in coeliac patients based on immune modulation by IL-10.

Celiac Disease (CD) occurs in patients with Type 1 Diabetes (T1D) ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD). In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD) on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients.

Celiac disease (CD) is a systemic autoimmune disease due to a dysregulated mucosal immune response to gluten and related prolamines in genetically predisposed individuals. It is a common disorder affecting ~1% of the general population, its incidence is steadily increasing. Changes in the clinical presentation have become evident since the 80s with the recognition of extra-intestinal symptoms like short stature, iron deficiency anemia, altered bone metabolism, elevation of liver enzymes, neurological problems. Recent studies have shown that the overall prevalence of extra-intestinal manifestations is similar between pediatric and adult population; however, the prevalence of specific manifestations and rate of improvement differ in the two age groups. For instance, clinical response in children occurs much faster than in adults. Moreover, an early diagnosis is decisive for a better prognosis. The pathogenesis of extra-intestinal manifestations has not been fully elucidated yet. Two main mechanisms have been advanced: the first related to the malabsorption consequent to mucosal damage, the latter associated with a sustained autoimmune response. Importantly, since extra-intestinal manifestations dominate the clinical presentation of over half of patients, a careful case-finding strategy, together with a more liberal use of serological tools, is crucial to improve the detection rate of CD.