Signs Of Celiac Disease Research Articles

Diagnosis of Celiac Disease in a Patient with Isolated Refractory Dyspepsia and GERD: A Case Report

Celiac disease is a chronic autoimmune illness that develops in genetically susceptible persons who consume gluten that causes damage to the small intestine. The average global prevalence of CD is between 0.5 and 1%, despite regional variations in the disease's frequency. In this report, we present a 34-year-old patient with a complaint of epigastric pain and burning with a history of nausea and vomiting. She complained of severe gastric pain, bloating, discomfort, burning, and digestive problems. Endoscopy and colonoscopy were performed due to her lower abdominal pain and it showed that the asymptomatic with isolated dyspepsia patient was diagnosed with celiac disease. Every six months, anti-TCG, IgG, and IgA levels were monitored and they improved at the same time that the patient's symptoms did. Endoscopy must be performed in young patients, who have no signs of celiac disease and have a positive laboratory test.

Accuracy of Serological Screening for the Diagnosis of Celiac Disease in Type 1 Diabetes Children.

Background and Objectives: Patients with type 1 diabetes (T1D) are considered at high-risk for developing celiac disease (CD). The purpose of our study was to determine the prevalence of CD among children who were followed in our unit for T1D using the latest ESPGHAN guidelines, and avoiding intestinal biopsies in some of the children. Materials and Methods: We performed a prospective monocentric study, which included 663 T1D children between June 2014 and June 2016. We considered CD according to serological (tissue transglutaminase (TGAs) and endomysium antibodies) results. Children were included either at the time of T1D diagnosis or during their follow up. We looked for clinical and biochemical signs of CD, and for T1D characteristics. Results: The children's ages ranged from 11 months to 18 years. CD was confirmed in 32 out of 663 patients with T1D, with a prevalence of 4.8%. CD was excluded in 619 children and remained uncertain for 12 children, who had positive TGAs without the required criteria. We found that 95% of T1D children express HLA-DQ2 and/or -DQ8, which was 2.4 times higher than in the general population. Conclusions: An intestinal biopsy could be avoided to confirm CD in the majority of T1D children. Silent forms of CD are frequent and screening is recommended for all patients. Importantly, repeated TGA assessment is required in HLA genetically predisposed T1D patients, while it is unnecessary in the 5% who are HLA-DQ2 and -DQ8 negative.

Clinical, Laboratory, and Histopathological Evaluation of 493 Patients Who Underwent Endoscopic Biopsy with a Presumptive Diagnosis of Celiac Disease: Association with Autoimmune Diseases.

Celiac disease is an immunological reaction provoked by gluten digestion in genetically vulnerable individuals in response to unknown environmental factors. It affects 0.7% of the world's population and occurs at a rate of 1% in most nations. We aimed to assess the clinical, laboratory, and histopathological characteristics of patients with a presumable diagnosis of celiac disease and to investigate the coexistence of autoimmune disorders. In this retrospective study, data were gathered from the medical files of a total of 493 individuals with a preliminary diagnosis of celiac disease who underwent endoscopic biopsies. Analysis was carried out for clinical, biochemical, and histological results, as well as the presence of autoimmune disease. Per the results of serological tests used in the diagnosis of celiac disease in this series, gliadin IgA and IgG positivities were found in 33.7% (n = 54/160) and 39.4% (n = 69/175) of patients; endomysium IgA and IgG positivities were detected in 37% (n = 88/238) and 18% (n = 30/167) of patients, while tissue transglutaminase IgA and IgG positivities were detected in 47.3% (n = 115/243) and 16.3% (n = 15/92) of patients, respectively. The incidence of patients with a CD3 level of ≥30% was 69.1% in 152 patients whose CD3 levels were tested. The general public and healthcare professionals need to be more aware of the prevalence and many signs of celiac disease. There is still a need to conduct the necessary research in this area. By boosting awareness, early diagnosis, and diet, it will be possible to prevent symptoms and negative consequences.

Assessment of oral manifestations in pediatric patients with celiac disease in relation to marsh types

To investigate the presence of molar-incisor hypoplasia and recurrent aphthous ulcers, the level of caries experience, and oral hygiene status, and to measure salivary flow rate, salivary buffer capacity, and salivary cariogenic microflora with Marsh types. A single-blind, prospective clinical study with 62 pediatric patients diagnosed with celiac disease with 64 controls. Clinical identification of molar-incisor hypomineralization (MIH) was followed according to the European Academy of Pediatric Dentistry criteria. DMFS and dfs index were used for the caries experience of each child. The clinical diagnosis of RAU was present or not. Oral hygiene was surveyed by recording the OHI-S and the CRT® Bacteria and Buffer Test was used to examine the cariogenic microflora of each child. The prevalence of MIH was 61% and the number of recurrent aphthous ulcers were significantly higher in children with celiac disease. There was no statistically significant difference in the CD group, when DMFS, dfs, and MIH parameters were investigated according to dietary compliance. Higher dietary compliance resulted in better oral hygiene status. There was an inverse relationship between the duration of celiac diagnosis and the presence of MIH. A positive relation was found between the duration of the disease and the severity of MIH. In addition to the higher S. mutans counts, the salivary flow rate was very low in children with celiac disease, indicating a positive correlation between poor dietary compliance and poorer oral hygiene. In children, enamel defects and recurrent mucosal lesions may be a sign of celiac disease. Higher numbers of dental caries in permanent teeth of children with celiac disease may be related to Marsh 2 type. The pediatricians and/or pediatric gastroenterologists should refer the chin with celiac disease to the pediatric dentist for the accurate treatment of intraoral manifestations of the disease itself.

Intussusception as Rare Presenting Sign of Pediatric Celiac Disease: A Case Series.

Intussusception is the most common cause of gastrointestinal obstruction in children and typically presents with acute abdominal pain. Intussusception usually occurs in children under the age of 3 in the ileocecal region. Over the past 5 years, multiple patients at the Children's Hospital of Philadelphia have been diagnosed with both intussusception and biopsy-confirmed celiac disease (CD). Intussusception may be a presenting sign of pediatric CD and should raise clinical suspicion for celiac screening, especially if it is a small bowel-small bowel intussusception that occurs after the age of 3 in a malnourished patient.

Questionnaire-based survey to determine an at-risk group for coeliac disease among school children in Moscow, Russia.

Coeliac disease (CD) is a chronic digestive disorder which presents indiverse ways and is under-diagnosed. The purpose of this study was to provide insights into suspected CD among Russian schoolchildren, through defining the percentage of participants in an 'at-risk' group for CD in a paediatric cohort, by means of a questionnaire as a primary screening tool. Russian school children of both sexes age 7-18 years were enrolled in a population-based study to identify individuals affected by CD. Each participant was presented with a structured questionnaire based on criteria that can be used to reveal symptomatic signs of CD. Following on, we developed a case-finding strategy for the 'at-risk' group, based on serological and genetic testing and, where possible, endoscopic examination of participants. 10.2% of questionnaire respondents (312/3070) were classified as an at-risk group. Pathobiological CD analysis of this group returned positive test results for 13.5% of participants (42/312), and 0.6% of them (2/312) had CD confirmed by biopsy sample analysis. Our findings suggest that at-risk groups among children with symptomatic or some oligosymptomatic CD presentations can be identified through adopting a questionnaire as part of a population-based screening survey, if generally accepted screening programs are inaccessible.

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

The Effects of Colchicine on the Histopathological Findings of Celiac Disease During Familial Mediterranean Fever Treatment.

Familial mediterranean fever (FMF) and Celiac Disease (CD) are both autoinflammatory and autoimmune diseases with common clinical features affecting the gastrointestinal system. Familial mediterranean fever may coexist with CD. Inflammatory cells and cytokines are up-regulated within the intestinal mucosa of patients with CD. In this perspective, lymphocyte infiltration to the lamina propria of the small intestinal mucosa is a critical pathological sign. In the present study, we aimed to find out whether the treatment of an FMF patient with colchicine affects the pathological signs of concomitant developed CD on the same patient. We retrospectively reviewed the medical records of 147 patients with FMF who were followed up in our center between 2015 and 2020. Of the 147 patients with FMF, 3 patients also had CD. In this report, we presented these 3 cases. The findings obtained in this study suggest that pathological findings may be misinterpreted in autoimmune diseases, such as CD, when patients administer anti-inflammatory treatments, such as colchicine.

Skin Manifestations and Coeliac Disease in Paediatric Population.

Celiac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion, affecting approximately 1% of the worldwide population. Extraintestinal symptoms may be present as the first signs of CD, years before the CD diagnosis is made. A great variety of extraintestinal manifestations may be associated with CD. Cutaneous manifestations represent the main extraintestinal manifestations, with dermatitis herpetiformis being the most common in patients with CD. In adults, it has been demonstrated that the role of a gluten-free diet is crucial not only for the recovery of signs and symptoms associated with CD but also for cutaneous manifestations, which often improve after gluten avoidance. In children with CD, the association with skin disorders is well documented regarding dermatitis herpetiformis, but studies considering other dermatological conditions, such as psoriasis and atopic dermatitis, are few. The prevalence and manifestations of dermatological disorders in celiac children are often different from those in adults, explaining the gap between these populations. In addition, the therapeutic role of a gluten-free diet in the improvement in skin alterations is not fully understood in children and in adult population except for dermatitis herpetiformis. Therefore, cutaneous CD symptoms need to be known and recognized by physicians despite their specialties to improve early CD diagnosis, which is critical for a better prognosis. This review describes the current scientific evidence on skin manifestations associated with CD in the pediatric population.

Low isolated ferritin levels without anemia: is gastrointestinal tract endoscopy sufficient to explain the cause?

The present study assesses the diagnostic significance of low ferritin levels in gastrointestinal diseases by evaluating the endoscopic findings of patients with low ferritin levels without anemia. The study included patients aged 0-18years who underwent an upper and lower gastrointestinal system endoscopy in the Pediatric Gastroenterology Department of our hospital. The patients were divided into three groups based on hemoglobin, and ferritin levels at the time of initial presentation and endoscopic and histopathological findings were recorded retrospectively. In the present study, 2391 pediatric patients were reviewed, among which 29% (n=699) had anemia, 23% (n=549) had low ferritin levels without anemia, and 48% (n=1143) did not have anemia. The most common symptoms were abdominal pain, dyspepsia, and growth retardation. When the endoscopy findings were compared with those of patients with non-anemic group, Helicobacter pylori gastritis (24%/17.6%) and celiac disease (6%/2.2%) were more common in low ferritin levels without anemia, which indicated a statistically significant difference (p=0.000/p=0.04). Helicobacter pylori gastritis and celiac disease were more commonly observed in association with low ferritin levels. Low ferritin levels without anemia can be an early and silent sign of celiac disease.

Diagnostic Value of Persistently Low Positive TGA-IgA Titers in Symptomatic Children With Suspected Celiac Disease

While the algorithm to diagnose celiac disease (CD) in children with elevated anti-transglutaminase IgA (TGA-IgA) titers (>10 times upper limit of normal, ULN) is well defined, the management of children with low TGA-IgA values represents a clinical challenge. We aimed to identify the diagnostic value of persistently low positive TGA-IgA titers in predicting CD in children. We retrospectively analyzed children with symptoms or signs of CD, not eligible for a no-biopsy approach. We included children with at least 2 TGA-IgA measurements, endomysial antibody (EMA) assessment and esophagogastroduodenoscopy with biopsies. TGA-IgA values were provided as multiples of ULN. Patients were classified in groups according to median TGA-IgA values: A (TGA-IgA>1 ≤ 5 × ULN; defined as "low-positive"), B (TGA-IgA > 5 < 10 × ULN; "moderate-positive"), and C (controls). Data of 281 children were analyzed. Of 162 children in group A, CD was diagnosed in 142 (87.7%), whereas normal duodenal mucosa was found in 20. In group B, all 62 children (100%) received a CD diagnosis. Group C included 57 controls. EMA were undetectable in 31 (15%) of mucosal atrophy cases. On the receiver-operating characteristic curve (area under the curve = 0.910), a mean value of 1.7 ULN showed a sensitivity of 81.4% and specificity of 81.8% to predict mucosal damage. Repeated low or moderate TGA-IgA values (<5 ULN or <10 ULN) are good predictors of a CD diagnosis. Symptomatic children with persistently low positive TGA-IgA titers should undergo esophagogastroduodenoscopy regardless of their EMA status.

Oral manifestations of celiac disease in French children

Celiac disease (CD) is an immune-mediated systemic disorder caused by ingestion of the gluten found in wheat, rye, and barley. The currently estimated prevalence in children is about 1%. CD is a chronic enteropathy with gastrointestinal manifestations including diarrhea, abdominal distension and weight loss, but extra-intestinal features are increasingly being reported. Dental and oral manifestations such as dental enamel defects (ED), delay in dental eruption, and recurrent aphthous stomatitis (RAS) are well-recognized manifestations of CD. The aim of this study was to compare the frequency of oral manifestations (ED, RAS and delay in dental eruption) on deciduous and permanent teeth between children with CD and a control population. An oral examination was performed on 28 CD children and 59 control children. All children were younger than 12 years old and had deciduous or mixed dentition. CD children had significantly more ED and RAS than the control group (67.9% vs. 33.9% P=0.004 and 50.0% vs. 21.8% P=0.011, respectively). No delay in dental eruption was observed in CD children. ED were mainly grade I and II of Aine's classification (color defects and slight structural defects). ED were more often seen on CD children's deciduous teeth than on permanent teeth (57.1% and 13.6%, respectively; P<0.001). The main teeth affected by ED are the second molar and canines of the deciduous teeth, and the first molar, central incisor, and lateral incisors of the permanent teeth. RAS and ED that were symmetrical in all quadrants and occurred firstly in teeth that mineralize during the first year of life both seem to be signs of CD. Thus, more information for dentists and pediatricians on these oral manifestations should help improve detection of CD.

Clinical features of non-classical celiac disease in children and adolescents

Introduction/Objective. Nonclassical celiac disease (CD) is characterized by a very heterogeneous and non-specific clinical presentation. The aim of this study was to determine the basic symptoms and clinical signs of this CD subtype in children and adolescents Methods. The study was based on a sample of 58 children and adolescent, 38 female and 20 male, ages 1.75 to 17.75 (10.01?4.62) years with a nonclassical CD diagnosed according to the European Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria from 1990 and 2012. Results. Except four patients who were between the ages of 1.75 to 2.50 years, all others were older than three years. The main clinical symptoms and signs suggestive of non-classical CD were anemia caused by iron deficiency (48.28%), short stature (34.48%), and intermittent abdominal pain (18.97%), anorexia with stagnation or weight loss (13.79%), and chronic constipation (6.9%). Thirty patients had one symptom or sign of the disease, 15 had two and 13 had three. In addition, 12 patients had dental enamel hypoplasia, 18 sideropenia without anemia and five mild isolated hypertransaminasemia. A gluten-free diet, apart from the dental enamel hypoplasia, has resulted in the withdrawal of all indicators of the disease. Conclusion. The main symptoms and clinical signs of nonclassical CD in children and adolescents were iron deficiency anemia, short stature and intermittent abdominal pain, and less frequently anorexia with stagnation or weight loss and chronic constipation. Excluding dental enamel hypoplasia, a gluten-free diet leads to a complete recovery of the patient.

Clinical evaluation of children with celiac disease: A single-center experience

The clinical findings of Celiac Disease (CD) change over time. Instead of classical symptoms such as diarrhea, growth retardation, abdominal bloating, atypical symptoms such as chronic constipation and abdominal pain may be the only sign of CD.

Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease.

Coeliac disease is a common small intestinal enteropathy which manifests following ingestion of gluten in genetically susceptible individuals. Since gluten was identified as the driving factor in coeliac disease, the gluten-free diet (GFD) has remained the mainstay of treatment. While most individuals will display improvement in symptoms and signs of coeliac disease following institution of the GFD, up to 30% will continue to experience symptoms and/or have persisting intestinal inflammation. These individuals can be classified as having non-responsive coeliac disease (NRCD), which may be associated with dietary indiscretion, slow healing, refractory coeliac disease, and/or an alternative condition. The purpose of this review is to provide an overview of the causes of NRCD in adults, highlight a systematic approach to investigate these patients, and appraise the latest management aspects of this subset of coeliac disease.

Recurrent aphthous stomatitis as the only clinical sign of celiac disease in obese adolescent - case report and literature review

Introduction. Recurrent aphthous stomatitis (RAS) is a relatively common oral mucosal lesion of unclear etiology. It occurs in otherwise healthy people, but also in various infectious and non-infectious diseases, including celiac disease (CD). We present an obese adolescent with RAS as the only clinical sign of CD. Case outline. An adolescent aged 15 2/12 years come with very pronounced RAS in previous five months. He had no other difficulties. The patient was obese from the age of 12. Other data were without peculiarities. On admission he was 165 cm tall (P25), obese (BMI 27 kg/m2), in the final stage of puberty, with stretch marks in the distal areas of the abdomen, thighs and gluteus and very pronounced pain-sensitive aphthae in the buccal and labial mucosa accompanied by swelling of the lips and perioral region. Except for lower serum iron levels (8 ?mol/l), routine laboratory blood tests were within the reference range. The serological test for CD was positive (antibodies to tissue transglutaminase IgA 78.5 U/ml, anti-endomysial antibodies IgA positive). Endoscopy revealed reflux esophagitis, without any other pathological findings. Stereomicroscopic and pathohistological analysis of the duodenal mucosa samples showed mild destructive enteropathy (Marsh IIIa). Pathohistological examination of the gastric mucosa revealed grade I-II lymphocytic gastritis. The urease test for Helicobacter pylori was negative. A gluten-free diet resulted in the withdrawal of aphthous stomatitis and no recurrence later. Conclusion. Within the differential diagnostic analysis of the RAS causes, CD should also be considered. Additionally, obesity does not exclude the presence of CD.

Changing Pattern of Childhood Celiac Disease Epidemiology: Contributing Factors.

Up until the 1960s and 1970s, diarrhea, malabsorption syndrome, and failure to thrive were the presenting symptoms and signs of celiac disease (CD) in young infants; however this disease was also at the same time reported to be disappearing. Indeed, clinical childhood CD was seen to transform into a milder form, resulting in an upward shift in age at diagnosis during the 1970s (and years later for many countries). This changing pattern of CD presentation then altered the epidemiology of the disease, with major differences between and within countries observed. An awareness of the changing clinical nature of CD and use of case-finding tools to detect even clinically silent CD became an important factor in this changing epidemiology. Countries report both low and high prevalence but it seems to be on the increase resulting in a population-based level of 1–2%. This paper discusses the potential causes and environmental factors behind these observed clinical changes, identifying new clues from different studies published at the time this transformation took place. For instance, it was found that breastfeeding postponed the diagnosis of the disease but did not altogether prevent it. Moreover, gluten introduction at a young age, specifically at the mean age of 2 months, seemed to also have a clear impact in inducing malabsorption syndrome and failure to thrive in young infants in addition to other factors such as gluten intake volume and type of cereal present in the weaning food. Further, the impact of cow's milk and its high osmolarity might have played an important role; humanized milk formulas were not yet invented. Future epidemiological studies on the contributing environmental factors to the shift in CD presentation are thus recommended for countries in which these changing clinical features are still being observed.

Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study

Background: Seronegative celiac disease (CD) poses a diagnostic challenge.Aims: Characterize and identify differences between seronegative and seropositive CD.Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980–2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression.Results: Of 315 CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p = .016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p ˂ .001) and Marsh I lesion (34.6% vs. 3.7%, p ˂ .001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD.Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.

Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies

Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD-specific antibody levels are just above cutoff or when small intestinal biopsies show low-grade injuries. To investigate the biological pathways involved in CD and select potential biomarkers to aid in CD diagnosis, RNA sequencing of duodenal biopsies from subjects with either confirmed Active CD (n = 20) or without any signs of CD (n = 20) was performed. Gene enrichment and pathway analysis highlighted contexts, such as immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty-nine potential CD biomarkers were selected based on differential expression and biological context. The biomarkers were validated by real-time polymerase chain reaction of eight RNA sequencing study subjects, and further investigated using an independent study group (n = 43) consisting of subjects not affected by CD, with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet, or with low-grade intestinal injury. Selected biomarkers were able to classify subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10, GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from subjects with no or low-grade intestinal injury that received a CD diagnosis based on biopsies taken at a later time point. A large number of pathways are involved in CD pathogenesis, and gene expression is affected in CD mucosa already in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries might discover pathways and biomarkers involved in early stages of CD pathogenesis.

Gliadin‐reactive T cells in Italian children from preventCD cohort at high risk of celiac disease

Newborns at high risk of celiac disease (CD) were recruited in Italy in the context of the PreventCD study and closely monitored for CD, from 4months up to a mean age of 8years at follow-up. The aim of our study was to investigate intestinal T-cell reactivity to gliadin at the first clinical and/or serological signs of CD. Gliadin-reactive T-cell lines were generated from intestinal biopsies of 19 HLA-DQ2-or HLA-DQ8-positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls. Immune reactivity was evaluated against gliadin and known immunogenic peptides from α-, γ-, or ω-gliadins. The role of deamidation by transglutaminase (tTG) in determining the immunogenicity of gliadin was also investigated. Most of the children with CD (either acute or potential) had an inflammatory response to gliadin. Notably, signs of T-cell reactivity to gliadin were also found in some non-celiac subjects, in which IFN-γ responses occurred mainly when regulatory IL-10 and TGF-β cytokines were blocked. Interestingly, PreventCD children reacted to gliadin peptides found active in adult CD patients, and tTG deamidation markedly enhanced gliadin recognition. T cells reactive to gliadin can be detected in the intestine of children at high risk of developing CD, in some cases also in the presence of a normal mucosa and negative CD-associated antibodies. Furthermore, children at a very early stage of CD recognize the same gliadin epitopes that are active in adult CD patients. Tissue transglutaminase strongly enhances gluten T-cell immunogenicity in early CD.