Pediatric Celiac Disease Research Articles

Validity of histology for the diagnosis of paediatric coeliac disease: a Swedish multicentre study

Objective Histological evaluation of intestinal biopsies for the diagnosis of coeliac disease can be challenging and compatible with risk of misdiagnosis. The aim was to evaluate the agreement of pathological diagnosis for coeliac disease in children investigated at four major paediatric university hospitals in Sweden. Materials and methods Intestinal duodenal biopsies were collected from 402 children at median 9.7 years (1.4–18.3 years). A pathologist at each hospital performed the primary evaluation. A designated pathologist, blinded to the primary evaluation, performed a second Marsh classification of biopsies (M0 to M3c) taken from the bulb and duodenum separately. Kappa (κ) scores between first and second evaluation determined the agreement. Plasma samples were collected at the day of intestinal biopsy and analysed for tissue transglutaminase autoantibodies (tTGA) using radioligand-binding assays. Results Marsh scores were concordant in 229/356 biopsies (64%, κ = 0.52, p < 0.0001). Among discordant results, 15/127 (12%) showed M0 in distal duodenum but ≥ M2 in the bulb, whereas the opposite was true for 8/127 (6%) of the biopsies. There were fewer collected duodenal biopsies, more missing bulb biopsies and missing CD3 staining among discordant evaluations. The second evaluation revealed a Marsh score compliant with coeliac disease in 22 children of whom seven children were tTGA positive. Conclusions The variation between university hospitals on the pathological evaluation of biopsies may lead to misdiagnosis of coeliac disease in paediatric patients. Access to clinical and endoscopic information as well as tTGA levels may be useful for the pathologist to complement the evaluation in dubious cases.

Genetic sharing and heritability of paediatric age of onset autoimmune diseases.

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts.

The clinical presentation of coeliac disease in 1030 Swedish children: Changing features over the past four decades

BackgroundThe features of paediatric coeliac disease have changed in recent decades. We hypothesised that the age at diagnosis might continue to increase, whereas the severity of symptoms should decrease. MethodsIn the present study, filed data on 1030 paediatric patients diagnosed with coeliac disease between 1973 and 2013 were analysed. The information available covered 99.8% of small bowel biopsies and included information on sex, age and clinical symptoms. ResultsThe age at diagnosis increased significantly, from a mean of 2.2 years during the first 10 years to 8.2 years in recent years. The proportion of children with severe symptoms declined from 92.8% to 78%, as did the proportion of biopsies characterised by severe pathology. In recent years, the monosymptomatic form of coeliac disease has been more common, and the number of patients detected at screening has increased. The frequency of patients with gastrointestinal symptoms, extra-intestinal symptoms, and failure to thrive and/or short stature at presentation decreased. ConclusionsThe mean age of newly diagnosed patients has increased over the last 15 years. Currently, coeliac disease shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, and adolescents from extra-intestinal manifestations.

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease.

Several factors support the view of inflammatory bowel disease [IBD] origin in the host responsiveness to intestinal bacteria, although no single bacterial species has been shown as a causative agent in the pathogenesis. Our aim was to analyse the fecal microbiota of paediatric IBD patients at different stages of the disease. In addition, the characteristics of immune response to the bacterial isolates showing very low abundance in IBD were studied. Fecal samples [1-3 samples/child] were collected from 10 paediatric patients with crohn's disease [CD], and 12 with ulcerative colitis [UC] and from 8 healthy children, for polyphasic microbiological analysis (culture, real-time polymerase chain reaction [PCR], and denaturing gradient gel electrophoresis). In addition, in vitro cytokine responses of peripheral blood mononuclear cells to the bacterial isolates, which showed very low abundance in IBD, were studied. Although predominant bacterial diversity was higher in IBD, the numbers of Lachnospiraceae and Coriobacteriaceae bacteria were lower in IBD patients as compared with control children [p < 0.05]. In addition, Ruminococcaceae population diversity was lower in IBD [p < 0.05] and correlated negatively with fecal calprotectin levels. Both abundance and diversity of bifidobacterial populations were lower in children with IBD [p < 0.05], and particularly low numbers of certain bifidobacterial isolates were detected. In CD, we found enhanced up-regulation of interleukin-6 transcripts and impaired RAR-related orphan receptor C response to bifidobacteria, whereas decreased interferon-gamma response was observed in both CD and UC. We demonstrate altered fecal microbiota in paediatric IBD, particularly low numbers and diversity of bifidobacterial populations. Interestingly, immunological response to bifidobacteria differed between paediatric CD patients and control children.

Liver involvement in pediatric celiac disease.

Celiac disease (CD) is an intestinal inflammatory disease that manifests in genetically susceptible individuals when exposed to dietary gluten. It is a common chronic disorder, with a prevalence of 1% in Europe and North America. Although the disease primarily affects the gut, the clinical spectrum of CD is remarkably varied, and the disease can affect many extraintestinal organs and systems, including the liver. The hepatic dysfunction presenting in CD ranges from asymptomatic liver enzyme elevations or nonspecific reactive hepatitis (cryptogenic liver disorders), to chronic liver disease. In this article, we review the clinical presentations and possible mechanisms of CD-related liver injury to identify strategies for the diagnosis and treatment of these disorders in childhood.

Homosistein, Vitamin B12 and Folic Acid Levels in Patients with Pediatric Celiac Disease

Introduction: Our aim in this study was to investigate effects of vitamin B12 and folic acid malabsorption to homocysteine levels in celiac patients.Materials and Methods: Between 2-17 years of ages 32 celiac patients before treatment, 14 celiac patient in remission and 30 healthy controls involved in this study. Homocystein levels were evaluated in all groups. In addition plasma levels of vitamin B12 and folic acid determined in celiac and remission groups.Results: Homocysteine levels as arithmetic mean±SD found 22.8±1.69 µmol/L in celiac group, 17.31±1.94 µmol/L in remission group and 15.21±1.69 µmol/L in control group. Folic acid levels as arithmetic mean±SD found 7.04±0.74 ng/ml in celiac patients and 12.95±1.9 ng/ml in remission group. There is statistically significant difference between folic acid and homocysteine levels of two groups p 0.05 . Conclusions: In our study homocysteine levels were found to be higher in celiac group than remission group. In this study, difference in folic acid levels between two groups may show that changes in folic acid levels related to changes in homocysteine levels.

Su1276 Use of Anti-TNF Therapy in Patients With Crohn's Disease Complicated by an Abdominal Phlegmon

when compared to UC patients (29/120, 242%, p < 0.001). The following types of EIM were observed: 37/266 (13.9%) peripheral arthritis / arthralgia (17.8% in CD vs. 9.2% in UC); 5/266 (1.9%) uveitis / iritis (2.7% in CD vs. 0.8% in UC; 26/266 (9.8%) oral aphthous ulcers (12.3% in CD vs. 6.7% in UC); 2/266 (0.8%) ankylosing spondylitis (0.7% in CD vs. 0.9% in UC); 5/266 (1.9%) erythema nodosum (2.7% in CD vs. 0.8% in UC); 2/266 (0.8%) pyoderma gangrenosum (0.7% in CD vs. 0.8% in UC). Conclusion: EIM appear in pediatric IBD patients in similar prevalence when compared to the adult population. As a general rule, EIM are more frequently observed in pediatric CD patients when compared to pediatric UC patients. The most frequent EIM are peripheral arthritis / arthralgia, followed by oral aphthous ulcers.

Methotrexate for maintaining remission in paediatric Crohn's patients with prior failure or intolerance to thiopurines: a multicenter cohort study.

Methotrexate [MTX] is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease [CD], but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in paediatric CD patients. A multicenter cohort of paediatric MTX users who stopped thiopurines due to ineffectiveness or intolerance between 2002 and 2012 were included and followed for at least 12 months. Relapse-free use was defined as steroid and biologics-free clinical remission after the introduction of MTX, and included intentional discontinuation of successful therapy before the end of the observation period. A total of 113 patients with CD in remission were followed while on MTX monotherapy, of whom 75 [66%] had failed on thiopurines and 38 [34%] had stopped thiopurines due to side effects. Median age at the introduction of MTX was 14 years [range 7 to 17], and 93% used the subcutaneous route. Kaplan-Meier analysis showed that 52% of the study cohort were still in steroid- and biologics-free remission after 12 months of MTX monotherapy, with a difference that did not reach significance between thiopurine-intolerant and thiopurine-failing patients [p = 0.21, log-rank test]. The findings of this cohort study suggest that MTX is an effective immunomodulator to maintain remission after stopping thiopurines. MTX maintenance should be considered before stepping up to anti-tumor necrosis factor alpha therapy. MTX is probably somewhat more effective in patients who stopped thiopurines due to side effects than in those who failed on thiopurines.

The hematologic manifestations of pediatric celiac disease at the time ofdiagnosis and efficiency of gluten-free diet

To determine the hematologic manifestations at the time of diagnosis of celiac disease in children and the effects of a gluten-free diet on hematologic signs upon follow-up. The records ofpatients with celiac disease who received a follow up examination at the Pediatric Gastroenterology Clinic between June 2006 and June 2013 were retrospectively examined. Ninety-one patients were included in the study. The mean age at diagnosis was 8.1 ± 4.21 years and 59 patients (64.8%) were female. Thirty-two patients (35.2%) had hematologic signs at the time of diagnosis. Anemia (24.2%) was the most common hematologic sign, followed by thrombocytosis (16.5%) and leukopenia (4.4%). The tTG IgA titers were screened in 80 of the 91 patients during diagnosis. Follow-up examinations found that remission for anemia (P = 0.0 17), thrombocytosis (P = 0.039), and decreases in tTG IgA titers (P = 0.034) were more prominent in patients who had followed a strict gluten-free diet. Approximately one-third of the celiac disease patients had hematologic manifestations at the time of diagnosis. Remission in hematologic signs and decrease in tTG IgA titers were more prominent in patients who had adhered to a gluten-free diet.

Evaluation of hearing loss in pediatric celiac patients

ObjectivesCeliac disease (CD) is a chronic immune-mediated enteropathy caused by the ingestion of gluten in genetically predisposed individuals. In some reports, sensorineural hearing loss (SNHL) has been identified as an extraintestinal symptom of CD. We aimed to further investigate the possible association between CD and SNHL by examining a greater number of pediatric CD patients. MethodsThe study was carried out from March to September 2014 and included 110 pediatric patients with biopsy-confirmed CD (220 ears) and 41 age- and sex-matched controls (82 ears); participants were evaluated by tympanometry and pure tone audiometry (frequency, 250–8000Hz frequency). ResultsAudiometric bone conduction thresholds were significantly different between the CD patients and the controls (p<0.05), but there were no significant differences in pure tone averages for air conduction (p>0.05). When the results for CD patients were analyzed according to duration of disease (≤36 months and >36 months), a significant difference in bone conduction thresholds (p<0.05) was noted, with significant increments at the later stages of disease. However, this difference was not sufficient to define clinical hearing loss, as the pure tone average thresholds remained below 20dB. ConclusionThese results indicate that subclinical hearing loss may be present in children with CD, which could presage more serious hearing impairments at older ages and later stages of the disease. Hearing screenings should be recommended for children with CD in order to prevent the potentially unfavorable effects of hearing loss on the emotional, behavioral, cognitive, and sensorimotor development of these patients.

Pediatric Celiac Disease Patients Who Are Lost to Follow-Up Have a Poorly Controlled Disease

Background: Follow-up of celiac disease (CD) patients is recommended for gluten-free diet (GFD) adherence monitoring and complication detection. We recently showed that 35% of children with CD were lost to follow-up (LTFU). We aimed to characterize LTFU population, and thus identify compliance barriers to GFD and follow-up. Methods: 50 LTFU patients were investigated using a telephone questionnaire, regarding frequency of follow-up, serology testing, and adherence to GFD (using the validated Biagi score). Fifty two regular follow-up patients served as controls. Results: LTFU patients had poor adherence to GFD (average Biagi score of 2.0 ± 1.4) compared to controls (3.0 ± 1.0, p < 0.001). Only 22% of LTFU performed periodic celiac serology testing compared to 82% of controls (p < 0.001). LTFU had higher prevalence of positive celiac serology tests (50% compared to 25% of controls, p = 0.01). Fewer LTFU were National Celiac Association members (24%) compared with controls (44%, p = 0.05). Regression analysis showed positive relationships between LTFU and poor adherence to GFD (R² = 0.26737, p = 0.001), older age at diagnosis (R² = 0.30046, p = 0.03), and non-membership in a celiac association (R² = 0.18591, p = 0.0001). Conclusion: LTFU is associated with non-adherence to GFD and positive serology. Risk factors for LFTU should be identified and addressed in order to improve patient care.

Advances in pediatric celiac disease.

To summarize the recent advances in celiac disease in children. New clues to the pathogenesis of celiac disease continue to emerge that may implicate the role of microbiome changes, antirotavirus VP7 antibodies, and the Parkinson's disease seven gene in celiac disease. Updated guidelines in pediatrics no longer support biopsies in all patients with celiac disease who have been identified by serology, clinical signs, and genetics. Serology screening of total immunoglobulin A in all patients may not be necessary in select patients. Prevalence and additional diseases associated with celiac disease continue to be elucidated. Our knowledge of celiac disease continues to grow with increasing evidence of the pathogenesis, genetics, diagnosis, and risk factors of the disease. Major changes have been made with respect to the guidelines for pediatric celiac disease, and potential improvements to simplify the algorithms for diagnosis and elimination of unessential testing have been proposed by new studies.

Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet

Objective. Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2–6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Materials and Methods. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Results. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 μM. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, <1400 μM, while 29.8% demonstrated high levels, that is, >1400 μM. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. Conclusion. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

The presence of anti-endomysial antibodies and the level of anti-tissue transglutaminases can be used to diagnose adult coeliac disease without duodenal biopsy.

The new ESPGHAN guidelines for diagnosis of paediatric coeliac disease suggest to avoid biopsy in genetically pre-disposed and symptomatic individuals with positive anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTG). However, duodenal biopsy remains the gold standard in adult coeliac disease. To establish the cut-off values of a-tTG, which would: predict the presence of duodenal histology (Marsh ≥2) diagnostic for coeliac disease; and predict the presence of villous atrophy (Marsh 3) in adults. We performed an observational prospective study including all consecutive adult patients with suspected coeliac disease. All subjects were tested for EMA and a-tTG. Coeliac disease diagnosis was made in presence of Marsh ≥2, a-tTG >7 U/mL and positive EMA. A ROC curve was constructed to establish the best specificity cut-off of a-tTG levels, which would predict the presence of Marsh ≥2 and Marsh 3 at histology. The study included 310 patients with positive antibodies. Histology showed Marsh 1 in 8.7%, Marsh 2 in 3.5%, Marsh 3 in 87.7%. The best cut-off value of a-tTG for predicting Marsh ≥2 was 45 U/mL (sensitivity 70%; specificity 100%; PPV 100%; NPV 24.1%); the best cut-off for predicting villous atrophy was 62.4 U/mL (sensitivity 69%, specificity 100%; PPV 100%; NPV 31%). The diagnosis of coeliac disease can be reached without histology in adult patients with positive EMA and a-tTG levels >45 U/mL. An a-tTG level >62.4 was diagnostic for villous atrophy. These results could contribute to improving the diagnosis of coeliac disease by allowing for a significant reduction in diagnosis-related costs.

Biological therapy and mucosal healing in a pediatric cohort affected by Crohn's disease

Objectives: Mucosal healing (MH) seems able to predict a sustained remission and anti-TNF alpha antibodies appear effective in achieving MH. Few studies evaluating MH as a therapeutic goal in pediatric CD are available.

Risk of pediatric celiac disease according to HLA haplotype and country: evidence-based-medicine viewpoint.

This multi-centric cohort study [1] from four countries followed a group of infants with the HLA haplotype DR3-DQ2 or DR4-DQ8, from birth through the first few years of life; seeking the appearance of antibodies to tissue transglutaminase (tTG) (labeled as celiac disease autoimmunity), and development of celiac disease. This was part of a larger study evaluating the development of type 1 diabetes in a cohort of infants with genetic susceptibility (based on carrying the HLA haplotype DR3-DQ2 or DR4-DQ8) [2]. Over a median follow-up duration of nearly five years, the investigators reported 12% prevalence of celiac disease autoimmunity and 3% prevalence of celiac disease. They also identified that the respective risks of these two outcomes varied by the HLA genotype: 26% and 11% with homozygosity for DR3-DQ2 haplotype; 11% and 3% with DR3-DQ2/DR4-DQ8 haplotype; 8% and 3% with DR4-DQ8 homozygosity; and 3% and <1% among those with DR4-DQ8/DR8-DQ4 haplotype. There was statistically significant higher risk of celiac disease autoimmunity and celiac disease in infants from Europe (highest risk in Sweden), female gender, and those with family history of celiac disease.

P-102: Bioavailability and tolerance of high doses vitamin D in children with newly diagnosed Crohn’s disease

Methods: We conducted an open label pilot study aiming to investigate the bioavailability and tolerance of high doses of vitamin D3 as an adjunct therapy in children with newly diagnosed pediatric CD. Vitamin D was administered orally at doses of 3,000 IU/day (in children with enteral nutrition therapy) or 4,000 IU/day (in children with corticosteroids). The primary objective was to document the lack of adverse effects (such as hypercalcemia or hypercalciuria). The secondary objective was to investigate the bioavailability of vitamin D, as assessed by the blood levels of 25OHD measured weekly up to one month. Results: A total of 20 children (9 girls, 11 17 years) were included in the study. CD localization at diagnosis was ileal (n = 5), colic (n = 5) and ileocolic (n = 10). All patients had active inflammatory phenotype. The median (range) level of 25(OH)D at baseline was 51 nmol/L (20 77). Vitamin D supplementation resulted in a gradual increase of 25(OH)D: slower during the first two weeks followed by a plateau by the end of the fourth week. All patients with a daily dose of 4,000 IU D3 reached a 25(OH)D blood level of 100 nmol/L. No patient had a serum level of vitamin D above 220 nmol/L (toxic level). We did not observe any adverse clinical or biological event during followup. Conclusion: In children with active CD at diagnosis, a daily dose of 4,000 IU of vitamin D is well tolerated and quickly increases the blood levels of 25OHD3 to 100 nmol/L or above in all cases.

HLA genotyping in pediatric celiac disease patients.

Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 90-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Children's Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1*02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development.

Risk of Pediatric Celiac Disease According to HLA Haplotype and Country

BackgroundThe presence of HLA haplotype DR3–DQ2 or DR4–DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).MethodsWe studied 6403 children with HLA haplotype DR3–DQ2 or DR4–DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies.ResultsThe median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3–DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3–DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4–DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25).ConclusionsChildren with the HLA haplotype DR3–DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease.

OBJECTIVES:Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.METHODS:Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.RESULTS:The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).CONCLUSIONS:A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.