Progression of Celiac Disease in Children With Antibodies Against Tissue Transglutaminase and Normal Duodenal Architecture

Auricchio, Renata; Mandile, Roberta; Vecchio, Maria Rosaria Del; Scapaticci, Serena; Galatola, Martina; Maglio, Mariantonia; Discepolo, Valentina; Miele, Erasmo; Cielo, Donatella; Troncone, Riccardo; Greco, Luigi

doi:10.1053/j.gastro.2019.04.004

Cited by 70 publications

(64 citation statements)

References 23 publications

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“…Potential CD is characterized by the presence of CD specific autoantibodies in sera (patients enrolled to our study had positive celiac specific autoantibodies both anti-tTG2-IgA and anti-EMA-IgA) and normal histology of the small intestine (described as Marsh 0 in modified Marsh-Oberhuber classification) or only increased number of IEL without other features of inflammation (described as Marsh 1). Recently, a long-term study of 280 children with potential CD on a gluten-containing diet has shown that the cumulative incidence of progression to active CD with villous atrophy was only 43% [27]. However, in our study, 2 of 3 children were followed for 3 years, and one of them (patient No 1) developed active CD, while the other (patients No 2) had persistently elevated levels of anti-tTG2-IgA.…”

Section: Discussioncontrasting

confidence: 59%

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Sowińska

Morsy

Czarnowska

et al. 2020

Cells

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Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset.

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Section: Discussioncontrasting

confidence: 59%

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Sowińska

Morsy

Czarnowska

et al. 2020

Cells

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“…In a subset, anti-TG2 antibodies may fluctuate or even disappear (60,61). Recently, factors predicting such evolution have been suggested, such as increased density of intraepithelial γδ T cells, small intestinal mucosal deposits of anti-TG2 antibodies, and HLA dose (62).…”

Section: Natural Historymentioning

confidence: 99%

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity

et al. 2020

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Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis.

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“…Thus, non-diagnostic duodenal biopsies do not exclude CD, and practice guidelines require follow-up endoscopy and additional biopsies in patients with clinical and serological evidence of CD (i.e., high pre-test probability) [14,17]. Longitudinal studies have also demonstrated histological evolution in patients who carry the diagnosis of CD based on clinical, serological and genetic data [48]. In these patients, duodenal histology at presentation can be non-diagnostic, suggesting that biopsy is an inherently suboptimal test in early CD.…”

Section: Pathophysiology Of CDmentioning

confidence: 99%

Value of Biopsy in a Cohort of Children with High-Titer Celiac Serologies: Observation of Dynamic Policy Differences between Europe and North America

Badizadegan¹,

Vanlandingham

Hampton

et al. 2020

Preprint

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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 practioners. Methods: We use retrospective clinical cohorts of 27,868 serum tissue transglutaminase (tTG) immunoglobulin A levels and 7,907 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 4,891 and 7,738 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 the forces that maintain the status quo in North America go beyond medical evidence and include a variety of social and economic factors. This work contributes to the growing body of evidence that suggests that the dynamics that largely favor maintaining status quo management policies extend to clinical medicine and influence a variety of clinical decisions at the level of individual patients and the population.

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Progression of Celiac Disease in Children With Antibodies Against Tissue Transglutaminase and Normal Duodenal Architecture

Cited by 70 publications

References 23 publications

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity

Value of Biopsy in a Cohort of Children with High-Titer Celiac Serologies: Observation of Dynamic Policy Differences between Europe and North America

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