Evidence supporting safe diagnosis of coeliac disease in children with antitissue transglutaminase titre ≥5 times upper limit of normal.

OBJECTIVE: European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on coeliac disease (CD) recommend that children who have IgA-based antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) and positive antiendomysial antibody, can be reliably diagnosed with CD via the no-biopsy pathway. The aim of this study was to examine the relationship between TGA-IgA ≥5×ULN and histologically confirmed diagnosis of CD. METHODS: Data including TGA-IgA levels at upper gastrointestinal endoscopy and histological findings from children diagnosed with CD following endoscopy from 2006 to 2021 were analysed. CD was confirmed by Marsh-Oberhuber histological grading 2 to 3 c. Statistical analysis was performed using χ² analysis (p<0.05= significant). RESULTS: 722 of 758 children had histological confirmation of CD. 457 children had TGA-IgA ≥5×ULN and 455 (99.5%) of these had histological confirmation for CD; the two that did not had eventual diagnosis of CD based on clinicopathological features. 114 of 457 had between TGA-IgA ≥5×ULN and <10×ULN, all had confirmed CD. The likelihood of a positive biopsy with TGA-IgA ≥5×ULN (455/457) compared with TGA-IgA <5×ULN (267/301) has strong statistical significance (p<0.00001). The optimal TGA-IgA cut-off from receiver operating characteristic curve analysis was determined to be below 5×ULN for the two assays used. CONCLUSION: 99.5% of children with TGA-IgA ≥5×ULN had histological confirmation of CD, suggesting that CD diagnosis can be made securely in children with TGA-IgA ≥5×ULN. If other studies confirm this finding, there is a case to be made to modify the ESPGHAN guidelines to a lower threshold of TGA-IgA for serological diagnosis of CD.

Positive tissue transglutaminase antibodies with negative endomysial antibodies: Unresolved issues in diagnosing celiac disease.

BACKGROUND: The serological screening for celiac disease (CD) is currently based on the detection of anti-transglutaminase (tTG) IgA antibodies, subsequently confirmed by positive endomysial antibodies (EMA). When an anti-tTG IgA positive/EMA IgA negative result occurs, it can be due either to the lower sensitivity of the EMA test or to the lower specificity of the anti-tTG test. This study aimed at verifying how variation in analytical specificity among different anti-tTG methods could account for this discrepancy. METHODS: A total of 130 consecutive anti-tTG IgA positive/EMA negative samples were collected from the local screening routine and tested using five anti-tTG IgA commercial assays: two chemiluminescence methods, one fluoroimmunoenzymatic method, one immunoenzymatic method and one multiplex flow immunoassay method. RESULTS: Twenty three/130 (17.7%) patients were diagnosed with CD. In the other 107 cases a diagnosis of CD was not confirmed. The overall agreement among the five anti-tTG methods ranged from 28.5% to 77.7%. CD condition was more likely linked to the positivity of more than one anti-tTG IgA assay (monopositive = 2.5%, positive with ≥ three methods = 29.5%; p = 0.0004), but it was not related to anti-tTG IgA antibody levels (either positive or borderline; p = 0.5). CONCLUSIONS: Patients with positive anti-tTG/negative EMA have a low probability of being affected by CD. Given the high variability among methods to measure anti-tTG IgA antibodies, anti-tTG-positive/EMA-negative result must be considered with extreme caution. It is advisable that the laboratory report comments on any discordant results, suggesting to consider the data in the proper clinical context and to refer the patient to a CD reference center for prolonged follow up.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Estimation of the celiac disease prevalence in Denmark and the diagnostic value of HLA-DQ2/DQ8.

The aims of the present study were to estimate the celiac disease (CD) prevalence in Denmark and the relevance of the test for human leukocyte antigen DQ2 and DQ8 haplotypes (HLA-DQ2/DQ8) for diagnosing CD. The plasma IgA transglutaminase antibody (TGA-IgA) and HLA-DQ2/DQ8 tests should normally be positive for a CD diagnosis. First, we estimated the CD and HLA-DQ2/DQ8 prevalence in the available blood samples collected at the North Zealand Hospital. Out of a total of 9754 patients, with symptoms suggestive of CD (such as malabsorption, diarrhea, steatorrhea, ion-deficiency anemia, and weight loss or growth failure), 153 patients had TGA-IgA positive results (i.e. TGA-IgA > 10 U/mL). In this cohort, the prevalence of CD was 0.912% and the prevalence of HLA-DQ2/DQ8 positive patients was estimated to be 62%. Based on the distribution of HLA-DQ2/DQ8 positive individuals in the general Danish population, a calculation of CD prevalence in Denmark was found to be maximum 0.77%. Second, we analysed for the HLA-DQ2/DQ8 haplotypes in 293 positive plasma TGA-IgA samples. Nearly all (99%) of the CD patients and non-CD patients were HLA-DQ2/DQ8 positive.

Value of biopsy in a cohort of children with high-titer celiac serologies: observation of dynamic policy differences between Europe and North America.

BACKGROUND: Healthcare systems implement change at different rates because of differences in incentives, organizational processes, key influencers, and management styles. A comparable set of forces may play out at the national and international levels as demonstrated in significant differences in the diagnostic management of pediatric Celiac Disease (CD) between European and North American practitioners. METHODS: We use retrospective clinical cohorts of 27,868 serum tissue transglutaminase (tTG) immunoglobulin A levels and 7907 upper gastrointestinal endoscopy pathology reports to create a dataset of 793 pathology reports with matching tTG results between July 1 of 2014 and July 1 of 2018. We use this dataset to characterize histopathological findings in the duodenum, stomach and esophagus of patients as a function of serum tTG levels. In addition, we use the dataset to estimate the local and national cost of endoscopies performed in patients with serum tTG levels greater than 10 times the upper limit of normal. RESULTS: Using evidence from a US tertiary care center, we show that in the cohort of pediatric patients with high pre-test probability of CD as determined by serum tTG levels, biopsy provides no additional diagnostic value for CD, and that it counter-intuitively introduces diagnostic uncertainty in a number of patients. We estimate that using the European diagnostic algorithms could avoid between 4891 and 7738 pediatric endoscopies per year in the US for evaluation of CD. CONCLUSIONS: This study considers the North American and European management guidelines for the diagnosis of pediatric CD and highlights the slow adoption in North America of evidence-based algorithms developed and applied in Europe for triage of endoscopy and biopsy. We suggest that system dynamics influences that help maintain the status quo in North America include a variety of social and economic factors in addition to medical evidence. This work contributes to the growing body of evidence that the dynamics that largely favor maintaining status quo management policies in a variety of systems extend to clinical medicine and potentially influence clinical decisions at the level of individual patients and the population.

ESPGHAN 'biopsy-sparing' guidelines for celiac disease in children with low antitransglutaminase during COVID-19.

OBJECTIVES: Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. METHODS: In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. RESULTS: Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. CONCLUSION: During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.

Celiac disease serology and gut microbiome following proton pump inhibitor treatment.

BACKGROUND: Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to proton pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome. METHODS: We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks. RESULTS: The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales. CONCLUSIONS: The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.

The Utility of IgA-Based Serologic Markers in Diagnosing Celiac Disease in Children 24 Months of Age or Younger.

Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age.

Raising the Cut-Off Level of Anti-Tissue Transglutaminase Antibodies to Detect Celiac Disease Reduces the Number of Small Bowel Biopsies in Children with Type 1 Diabetes: A Retrospective Study.

OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.

Progress in the serology-based diagnosis and management of adult celiac disease.

Introduction: This article provides a comprehensive overview of the development and application of serological tests used routinely in clinical practice for the diagnosis and management of adult celiac disease.Areas covered: We summarize existing scientific literature related to anti-endomyseal, anti-tissue transglutaminase, and anti-deamidated gliadin peptide antibodies and detail the current and potential future applications of these tests in celiac disease.Expert commentary: Current serological tests in celiac disease have some of the best performance characteristics among disease-specific tests. However, in adult celiac disease, current diagnostic algorithms still rely on duodenal biopsies to confirm the diagnosis. A 'biopsy avoidance strategy' has been implemented in pediatric celiac disease. Future high-quality studies will help inform on whether this approach can be implemented into adult gastroenterology services. It is envisaged that the next 5 years will see an increasing reliance on serology in the diagnosis of adult celiac disease.

Transglutaminase 3 Promotes Skin Inflammation in Atopic Dermatitis by Activating Monocyte-Derived Dendritic Cells via DC-SIGN.

Atopic dermatitis (AD) is often concomitant with increased levels of IgE against not only foreign allergens but also autoallergens. AD patients with autoallergy are likely to be more severe and difficult to treat, and self-reactive IgE might be a contributing factor in the pathogenesis of AD. However, how autoallergens are recognized by the immune system and what immune responses are induced subsequently remain largely unknown. We found that the serum level of IgE against transglutaminase 3 (TGase3) was significantly higher in AD patients than in healthy individuals and was positively correlated with disease severity. The expression of TGase3 in the lesional skin of AD patients was markedly increased compared with that of the controls, and Th2 cytokines and/or allergen promoted the expression of TGase3 in keratinocytes. TGase3 bond monocytes-derived dendritic cells (MoDCs) via dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), which resulted in the production of IL-6 and activation of the NF-κB signaling pathway in MoDCs; and TGase3-treated MoDCs facilitated Th1 polarization. Moreover, skin inflammation in the mouse model of MC903-induced AD was attenuated when TGase3 was inhibited. In conclusion, TGase3 was revealed as an autoallergen in AD and actively involved in skin inflammation; TGase3-targeting might be a therapeutic strategy for the treatment of AD.

Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients.

Seminal plasma, because of its proximity to prostate, is a promising fluid for biomarker discovery and noninvasive diagnostics. In this study, we investigated if seminal plasma proteins could increase diagnostic specificity of detecting primary prostate cancer and discriminate between high- and low-grade cancers. To select 147 most promising biomarker candidates, we combined proteins identified through five independent experimental or data mining approaches: tissue transcriptomics, seminal plasma proteomics, cell line secretomics, tissue specificity, and androgen regulation. A rigorous biomarker development pipeline based on selected reaction monitoring assays was designed to evaluate the most promising candidates. As a result, we qualified 76, and verified 19 proteins in seminal plasma of 67 negative biopsy and 152 prostate cancer patients. Verification revealed a prostate-specific, secreted and androgen-regulated protein-glutamine gamma-glutamyltransferase 4 (TGM4), which predicted prostate cancer on biopsy and outperformed age and serum Prostate-Specific Antigen (PSA). A machine-learning approach for data analysis provided improved multi-marker combinations for diagnosis and prognosis. In the independent verification set measured by an in-house immunoassay, TGM4 protein was upregulated 3.7-fold (p = 0.006) and revealed AUC = 0.66 for detecting prostate cancer on biopsy for patients with serum PSA ≥4 ng/ml and age ≥50. Very low levels of TGM4 (120 pg/ml) were detected in blood serum. Collectively, our study demonstrated rigorous evaluation of one of the remaining and not well-explored prostate-specific proteins within the medium-abundance proteome of seminal plasma. Performance of TGM4 warrants its further investigation within the distinct genomic subtypes and evaluation for the inclusion into emerging multi-biomarker panels.

CD44, TGM2 and EpCAM as novel plasma markers in endometrial cancer diagnosis.

BACKGROUND: Endometrial cancer (EC) is the most common malignancy of the female reproductive tract. Despite years of research, the accurate screening strategy is still not available in this disease and it is usually diagnosed only after the clinical signs are present. The recent technological advances in analytical methodologies enabled detection of multiple molecules in one, small sample of biological materials. Such approach was undertaken in the presented study. METHODS: Concentrations of aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), carbonic anhydrase IX (CA9), CD44, epithelial cell adhesion molecule (EpCAM), hepsin, kallikrein-6, mesothelin, midkine, neural cell adhesion molecule L1 (L1CAM), and transglutaminase 2 (TGM2) were measured using MAGPIX®System in plasma samples of 45 EC, 20 healthy controls and 11 patients with endometriosis. RESULTS: Significantly increased concentration in EC as compared to healthy controls were found in case of CD44 (p <  0.001), EpCAM (p = 0.033) and TGM2 (p <  0.001). EpCAM and mesothelin concentrations differed based on FIGO stages. Regression analysis revealed marker panels with high accuracy in detection of EC. The highest AUC 0.937 was attributed to the 3-marker panel of CD44/TGM2/EpCAM (84% sensitivity, 100% specificity), FIGO IA samples were discriminated from more advanced stages of EC with the mesothelin/grade 1 model featuring AUC of 0.911 (95.24% sensitivity, 78.26% specificity). CONCLUSIONS: Novel plasma biomarkers presenting good accuracy in diagnosing EC were found with TGM2 reported for the first time as plasma marker. It was also revealed that endometriosis may share similarities in the pattern of markers alterations characteristic for EC.

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.

Comparison of celiac disease markers in women with early recurrent pregnancy loss and normal controls.

PROBLEM: Celiac disease (CD) is an autoimmune intestinal inflammatory disease triggered by gluten in the diet. Untreated CD has been associated with pregnancy loss and infertility. The purpose of this study was to screen unselected women with recurrent pregnancy loss (RPL) for markers of CD to determine whether a correlation exists between RPL and CD serum markers. METHOD OF STUDY: Frequencies of three serum markers of CD [tissue transglutaminase (TTG) IgA, endomysial (EMA) IgA, and deaminated gliadin peptide (DGP) IgA] were determined by enzyme-linked immunoassay (ELISA). Seven hundred and eight women who had two or more failed clinical pregnancies (cases) and one hundred women with at least one live birth and no miscarriages (controls) were included in this study. All cases had a full workup for RPL based on the American Society for Reproductive Medicine 2013 guidelines. Antiphospholipid antibodies (aPL) were correlated with CD markers based on their potential prothrombotic role. Results The results show no significant difference in the prevalence of CD autoantibodies when comparing the RPL patients with the controls. Over half of the patients who tested positive for serum markers for CD also had positive aPL. Conclusion Screening unselected women with RPL who are asymptomatic for CD is not supported based on these data. Women who test positive for CD may be candidates for aPL testing based on the association of adverse pregnancy outcomes.

Synthetic Neoepitopes of the Transglutaminase-Deamidated Gliadin Complex as Biomarkers for Diagnosing and Monitoring Celiac Disease.

BACKGROUND & AIMS: Celiac disease (CeD) has characteristics of an autoimmune disease, such as increased antibody levels to tissue transglutaminase (tTG). However, assays to measure these biomarkers in blood samples do not identify patients with sufficient accuracy for diagnosis or monitoring of CeD. We aimed to discover biomarkers of CeD derived from neoepitopes of deamidated gliadin peptides (DGP) and tTG fragments and to determine if immune reactivity against these epitopes can identify patients with CeD with mucosal healing. METHODS: We analyzed serum samples from 90 patients with biopsy-proven CeD and 79 healthy individuals (controls) for immune reactivity against the tTG-DGP complex (discovery cohort). A fluorescent peptide microarray platform was used to estimate the antibody-binding intensity of each synthesized tTG-DGP epitope. We validated our findings in 82 patients with newly diagnosed CeD and 217 controls. We tested the ability of our peptide panel to identify patients with mucosal healing (based on the histologic analysis) using serum samples from patients with treated and healed CeD (n = 85), patients with treated but unhealed CeD (n = 81; villous atrophy despite a adhering a gluten-free diet), patients with untreated CeD (n = 82) and disease controls (n = 27), villous atrophy without CeD), and healthy controls (n = 217). Data were analyzed using principal component analysis followed by machine learning and support vector machine modeling. RESULTS: We identified 172 immunogenic epitopes of the tTG-DGP complex. We found significantly increased immune reactivity against these epitopes vs controls. In the both cohort, the set of neoepitopes derived from the tTG-DGP complex identified patients with CeD with 99% sensitivity and 100% specificity. Serum samples from patients with untreated CeD had the greatest mean antibody-binding intensity against the tTG-DGP complex (32.5 ± 16.4). The average antibody-binding intensity was significantly higher in serum from patients with treated but unhealed CeD mucosa (15.1 ± 7.5) than in patients with treated and healed CeD mucosa (5.5 ± 3.4) (P < .001). The assay identified patients with mucosa healing status with 84% sensitivity and 95% specificity. CONCLUSIONS: We identified immunogenic epitopes of the tTG-DGP complex, and found that an assay to measure the immune response to epitopes accurately identified patients with CeD, as well as patients with mucosal healing. This biomarker assay might be used in detection and monitoring of patients with CeD.

Elevated anti-tissue transglutaminase antibodies in children newly diagnosed with type 1 diabetes do not always indicate coeliac disease.

AIM: Elevated levels of anti-tissue transglutaminase (anti-tTG) antibody may spontaneously normalise in children with newly diagnosed type 1 diabetes, even if they eat gluten. The prevalence of this phenomenon and predictors of a subsequent coeliac disease (CD) diagnosis were determined. METHODS: The medical records of children diagnosed with type 1 diabetes at Ha'Emek Medical Centre, Israel, from 2007 to 2015, were retrospectively reviewed for elevated anti-tTG antibody levels. Demographic, clinical, laboratory and histological findings were compared between CD patients and those with transient coeliac serology. RESULTS: Of 425 patients with new onset type 1 diabetes, 34 (8%) had elevated anti-tTG antibodies: CD was diagnosed in 14, anti-tTG normalisation occurred in 13 and duodenal biopsies did not suggest CD in seven without anti-tTG antibody normalisation. Protective factors for a subsequent CD diagnosis were older age (p = 0.009) and mildly elevated anti-tTG antibody levels at the time of the type 1 diabetes diagnosis (p = 0.007), and decreased anti-tTG levels within six months of diagnosis (p = 0.03). CONCLUSION: Serological follow-up of a diet containing gluten is recommended for children who have newly diagnosed type 1 diabetes and slightly elevated anti-tTG antibodies with no symptoms that suggest CD.