Rapid diagnosis of celiac disease based on plasma Raman spectroscopy combined with deep learning.

Celiac Disease (CD) is a primary malabsorption syndrome resulting from the interplay of genetic, immune, and dietary factors. CD negatively impacts daily activities and may lead to conditions such as osteoporosis, malignancies in the small intestine, ulcerative jejunitis, and enteritis, ultimately causing severe malnutrition. Therefore, an effective and rapid differentiation between healthy individuals and those with celiac disease is crucial for early diagnosis and treatment. This study utilizes Raman spectroscopy combined with deep learning models to achieve a non-invasive, rapid, and accurate diagnostic method for celiac disease and healthy controls. A total of 59 plasma samples, comprising 29 celiac disease cases and 30 healthy controls, were collected for experimental purposes. Convolutional Neural Network (CNN), Multi-Scale Convolutional Neural Network (MCNN), Residual Network (ResNet), and Deep Residual Shrinkage Network (DRSN) classification models were employed. The accuracy rates for these models were found to be 86.67%, 90.76%, 86.67% and 95.00%, respectively. Comparative validation results revealed that the DRSN model exhibited the best performance, with an AUC value and accuracy of 97.60% and 95%, respectively. This confirms the superiority of Raman spectroscopy combined with deep learning in the diagnosis of celiac disease.

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Assessment of Skin Autofluorescence and Its Association with Glycated Hemoglobin, Cardiovascular Risk Markers, and Concomitant Chronic Diseases in Children with Type 1 Diabetes.

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D). MATERIALS AND METHODS: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation. RESULTS: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001). CONCLUSION: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

IgE to wheat, prick test, and Patch test among children with celiac disease.

INTRODUCTION AND AIM: Celiac disease is one of the most common autoimmune disorders. This study aimed to evaluate the relationship between celiac disease and wheat sensitization. SUBJECTS AND METHODS: In the current study, children aged < 18 years with confirmed celiac disease were included. Data were analyzed using SPSS. RESULTS: Gastrointestinal problems were the most common indication for evaluation in terms of celiac disease. Prick and patch tests were positive in 43.4% and 34% respectively. CONCLUSION: Prick test and patch test for wheat sensitization were positive in about 30-45% of the children for celiac disease.

Did diet compliance and remission reduce oxidative stress in celiac patients?

OBJECTIVE: We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet. METHODS: Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year. RESULTS: While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 µmol/L vs. 365.3±44.0 µmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 µmol/L down to 8.9±4.2 µmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001). CONCLUSION: Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.

Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

INTRODUCTION: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. METHODS: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. RESULTS: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. DISCUSSION: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.

Diagnosis of Seronegative and Ultrashort Celiac Disease.

In its conventional form, celiac disease (CeD) is characterized by both positive serology and flat villi in the duodenum, and is well known by gastroenterologists and general practitioners. The aim of this review was to shed light on 2 neglected and not yet well-defined celiac phenotypes, that is, seronegative and ultrashort CeD. Seronegative CeD can be suspected in the presence of flat villi, positive HLA-DQ2 and/or HLA-DQ8, and the absence of CeD antibodies. After ruling out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histologic improvements after 1 year of a gluten-free diet. Ultrashort CeD is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serologic positivity. Data on the prevalence, clinical manifestations, histologic lesions, genetic features, and outcome of seronegative and ultrashort CeD are inconclusive due to the few studies available and the small number of patients diagnosed. Some additional diagnostic tools have been developed recently, such as assessing intestinal transglutaminase 2 deposits, flow cytometry technique, microRNA detection, or proteomic analysis, and they seem to be useful in the identification of complex cases. Further cooperative studies are highly desirable to improve the knowledge of these 2 still-obscure variants of CeD.

Zonulin as a Biomarker for the Development of Celiac Disease.

OBJECTIVES: Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability. METHODS: We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin. RESULTS: Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = ß = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04). CONCLUSIONS: Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.

Circulating anti-hypothalamus antibodies in celiac patients: tissue transglutaminase friend or foe?

Celiac disease (CD) is an autoimmune disease with inflammatory characteristics, having a condition of chronic malabsorption, affecting approximately 1% of the population at any age. In recent years, a concrete correlation between eating disorders and CD has emerged. Hypothalamus plays a central role in determining eating behaviour, regulating appetite and, consequently, food intake. One hundred and ten sera from celiac patients (40 active and 70 following a gluten-free diet) were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. In addition, ghrelin was measured by ELISA. As control, 45 blood serums from healthy age matched were analysed. Among active CD, all patients resulted positive for anti-hypothalamus autoantibodies and sera showed significantly higher levels of ghrelin. All of the free-gluten CD were negative for anti-hypothalamus autoantibodies and had low levels of ghrelin, as well as healthy controls. Of interest, anti-hypothalamic autoantibodies directly correlate with anti-tTG amounts and with mucosal damage. In addition, competition assays with recombinant tTG showed a drastically reduction of anti-hypothalamic serum reactivity. Finally, ghrelin levels are increased in CD patients and correlated with anti-tTG autoantibodies and anti-hypothalamus autoantibodies. This study demonstrates for the first time the presence of anti-hypothalamus antibodies and their correlation with the severity of the CD. It also allows us to hypothesize the role of tTG as a putative autoantigen expressed by hypothalamic neurons.

Characterization of acquired anemia in children by iron metabolism parameters.

Inflammatory states are associated with anemia of chronic disease and acute infection. Hepcidin, a regulator of iron metabolism, is involved in iron pathophysiology during inflammation. We investigated biochemical characteristics in children with anemia from different causes. Four patient groups (n = 38; mean age: 12.44 ± 4.35 years) were studied: (1) inflammatory bowel disease (IBD, 10 patients); (2) iron deficiency anemia (IDA, 12); (3) celiac disease (CD, 8); (4) acute infection (AI, 8). Laboratory measurements were evaluated at diagnosis: blood count, serum iron, transferrin, ferritin, vitamin B12, folic acid, CRP, erythropoietin, hepcidin and soluble transferrin receptor (sTfR). IDA patients had the lowest Hgb (6.9 ± 1.7 g/dL), MCV (63.2 ± 7.2 fL), iron (16.8 ± 13.5 µg/dL), ferritin (4.5 ± 4.5 ng/mL) and hepcidin (3.1 ± 0.8 ng/mL) values, and the highest transferrin and sTfR values. AI patients had the highest ferritin (156.2 ± 124.5 ng/mL), CRP (144.6 ± 94 mg/L) and hepcidin (74.67 ± 12.3 ng/ml) values. Overall, hepcidin levels correlated with CRP and with ferritin (r = 0.83 and 0.85, respectively). Elucidating specific etiology-related biochemical profiles in pediatric patients with anemia from different causes using a combination of laboratory biomarkers, including hepcidin, can help physicians treat the anemia.

Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Serologic Testing for Celiac Disease in Graves' Hyperthyroidism: Should We Act Early?

BACKGROUND: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves'Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. MATERIALS AND METHODS: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG - AGA and IgA - AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. RESULTS: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. CONCLUSION: Due to possibility of false seropositivity of celiac antibodies in patients with Graves' thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.

Antitissue transglutaminase antibodies' normalization after starting a gluten-free diet in a large population of celiac children-a real-life experience.

INTRODUCTION: Few data are available regarding the trend of IgA anti-transglutaminase antibodies (TGA-IgA) in children with celiac disease (CD) on a gluten-free diet (GFD). Our aim is to examine the normalization time of CD serology in a large pediatric population, and its predictors. MATERIAL AND METHODS: We retrospectively evaluated the normalization time of TGA-IgA and its predictive factors (age, sex, ethnicity, symptoms, associated diabetes/thyroiditis, Marsh stage, TGA-IgA and endomysial antibody levels at diagnosis, diet adherence), in 1024 children diagnosed from 2000 to 2019 in three pediatric Italian centers, on a GFD. RESULTS: TGA-IgA remission was reached in 67,3%, 80,7%, 89,8% and 94,9% after 12, 18, 24 and 36 months from starting a GFD, respectively (median time = 9 months). TGA-IgA >10´upper limit of normal at diagnosis (HR = 0.56), age 7-12 years old (HR = 0.83), poor compliance to diet (HR = 0.69), female sex (HR = 0.82), non-Caucasian ethnicity (HR = 0.75), and comorbidities (HR = 0.72) were independent factors significantly associated with longer time to normalization. CONCLUSIONS: Our population is the largest in the literature, with the majority of patients normalizing CD serology within 24 months from starting a GFD. We suggest a special attention to patients with comorbidities, language barriers or age 7-12 years for a proper management and follow-up.

Delayed presentation of seropositivity in pre-existent coeliac disease in patients with Type 1 diabetes mellitus: a possible co-occurrence?

OBJECTIVE: The co-occurrence of coeliac disease (CD) and type 1 diabetes mellitus (T1DM) is well described and is mainly explained by sharing of common pathogenic mechanisms, such as common high-risk human lymphocyte antigen (HLA) genotypes (DR-DQ). PATIENTS AND METHODS: We describe a 12-year-old female patient with T1DM who presented with prolonged and severe glucose dysregulation. Extensive investigations, including coeliac screen, were negative. RESULTS: 3 years after glucose dysregulation manifested, coeliac screen testing was positive and coeliac disease was confirmed with bowel biopsy. Compliance to a gluten-free diet resulted in improvement of glucose control and seronegativity 9 months post-diagnosis. CONCLUSIONS: This is the first case report describing delayed seropositivity of CD and suggests that CD enteropathy may precede positive serology and could cause severe glucose dysregulation in patients with T1DM.

Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. Conclusions: We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.

Esophageal Eosinophilia and Eosinophilic Esophagitis in Celiac Children: A Ten Year Prospective Observational Study.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. METHODS: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia; at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. RESULTS: A total of 465 children (M 42% mean age 7.1 years (range: 1-16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54-2.9%). Only one child was diagnosed as eosinophilic esophagitis; we calculated a prevalence of 0.3% (95% CI: 0.2-0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89-47.7%; p = 0.06) than in the general population. CONCLUSION: The finding of an increased number of eosinophils (>15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

Screening of Altered Metabolites and Metabolic Pathways in Celiac Disease Using NMR Spectroscopy.

BACKGROUND: Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. METHOD: We compared the serum metabolic profile of CeD patients (n = 42) and healthy controls (n = 22) using NMR spectroscopy and multivariate analysis. RESULT: 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients' samples compared with healthy controls (p < 0.05). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. CONCLUSION: In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

Clinical Value of Tissue Transglutaminase Antibodies in Celiac Patients over a Long Term Follow-Up.

INTRODUCTION & AIM: Anti-tissue transglutaminase antibody (tTGA) titer is used during the follow-up of celiac patients to evaluate gluten-free diet (GFD) responsiveness. However, no clear data are available on this issue. The aim of this study was to evaluate tTGA significance during celiac disease (CD) monitoring. METHODS: From January 2017 to January 2020, consecutive CD patients on a GFD with persistent positive tTGA were enrolled. Antibody titres were evaluated on a yearly basis from CD diagnosis to the last follow-up. Urinary gluten detection tests, duodenal histology and capsule enteroscopy (CE) were performed. A tTGA-positive cohort was compared with a control group composed of 212 treated CD patients with negative tTGA. RESULTS: 65 patients (12% males, median age at enrollment and CD diagnosis, 37 (14-86) and 31 (1-76), respectively, median follow up 4 (1-26) years) presented with positive tTGA during follow-up. Overall, the tTGA titres were 3 (1-79) fold increased (ULN). Three different tTGA trends were recognized: (I) 36 (55%) patients with a progressive titres decrease; (II) 16 (25%) patients with a fluctuating behavior; (III) 13 (20%) patients with a steady state or increased titres. tTGA+ patients did not present with different clinical and demographic parameters. Duodenal atrophy was present in 10% vs. 36% of the tTGA positive vs. negative group (p < 0.005), respectively. Gluten detection results were positive in 3 (8%) cases, all in the III group. In tTGA+ patients, CE did not identify any CD-related complications. CONCLUSIONS: tTGA positivity during CD follow up did not present a relevant clinical significance without association with autoimmune comorbidities and mucosal damage.

The prevalence, immune profile, and clinical characteristics of children with celiac disease and type 1 diabetes mellitus in the state of Qatar.

OBJECTIVES: Children with antibody positive type 1 diabetes mellitus (type 1 diabetes) are at an increased risk of developing celiac disease (CD) which suggests a common autoimmune basis with both high-risk human lymphocyte antigen (HLA) and non-HLA factors playing a role in the pathophysiology. We aim to describe the prevalence, immune profile, and clinical characteristics of children with CD who have type 1 diabetes mellitus in Qatar. METHODS: All children (aged 0-18 years) attending a regional diabetes clinic with antibody positive type 1 diabetes were screened for CD. Measurement of tissue transglutaminase IgA and IgG as well as anti-endomysial antibody, was done, clinical details about the birth history, family history of diabetes and CD, age of onset, and ethnicity were collected. RESULTS: Out of the 1,325 children with antibody positive type 1 diabetes, 54 were identified to have CD on screening and then confirmed on small bowel biopsy. The prevalence of CD in the type 1 diabetes childhood population in Qatar is 4.07%. CD and type 1 diabetes were more prevalent in the Qatari children (n=32) as compared to non-Qatari (n=22) and occurred mostly in the age group 6-10 years. The most common type 1 diabetes antibodies in children with CD were glutamic acid decarboxylase and insulin autoantibody. Twelve subjects were asymptomatic for CD symptoms and picked up only on screening. CONCLUSIONS: The prevalence of CD in children with type 1 diabetes in Qatar is comparable to reports from around the world. Many children were asymptomatic and thus routine screening is recommended.