Search

BACKGROUND: . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients.OBJECTIVES: To identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD).METHODS: . We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25-58) and at least Marsh 2 histology.RESULTS: . Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis.CONCLUSION: . Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.

SummaryDifferent regions of the gastrointestinal tract have distinct digestive and absorptive functions, which may be locally disrupted by infection or autoimmune disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. Here, we used mouse models, transcriptomics, and immune profiling to show that regional epithelial expression of the transcription factor GATA4 prevented adherent bacterial colonization and inflammation in the proximal small intestine by regulating retinol metabolism and luminal IgA. Loss of epithelial GATA4 expression increased mortality in mice infected with Citrobacter rodentium. In active celiac patients with villous atrophy, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. This study reveals broad impacts of GATA4-regulated intestinal regionalization and highlights an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.One-sentence summaryEpithelial GATA4 regulates intestinal regionalization of bacterial colonization, metabolic pathways, and tissue immunity.

Background and aims: Celiac disease (CeD) is a gluten triggered, immune-mediated disease of the small intestine. Few clinical cohort descriptions are available, despite the diverse clinical picture. This study provides an overview of a large Dutch CeD cohort focusing on presenting symptoms, co-occurrence of immune mediated diseases (IMD) and malignancies.Methods: We performed a retrospective study in a Dutch university and a non-university medical hospital and included only biopsy proven (>= Marsh type 2 classification) CeD patients.Results: 412 patients were included, selected from 9468 small-bowel biopsy pathology reports and financial codes.Classical symptoms were present in approximately one third of the cohort (diarrhea (37.4%), fatigue (35.0%), weight loss (31.6%), abdominal pain (33.3%)). Atypical symptoms as constipation (10.4%) and reflux (12.4%) were reported as well. 11.7% was diagnosed without reported symptoms.In 25.2% concomitant IMD occurred (most prevalent: type 1 diabetes mellitus (4.9%), microscopic colitis (4.9%), immune mediated-thyroid disease (4.1%)). CeD patients with a concomitant IMD were diagnosed at a significantly higher age compared to those without (P = 0.002). Malignancies occurred in 53 cases (12.9%), including eight Enteropathy Associated T-cell Lymphomas.Conclusion: This is the first study describing a CeD cohort in such detail in the Netherlands and highlights the clinical heterogeneity and importance of screening for concomitant diseases in CeD. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Celiac disease (CeD) is a complex immune-mediated disorder that is triggered by dietary gluten in genetically predisposed individuals. CeD is characterized by inflammation and villous atrophy of the small intestine, which can lead to gastrointestinal complaints, malnutrition, and malignancies. Currently, diagnosis of CeD relies on serology (antibodies against transglutaminase and endomysium) and small-intestinal biopsies. Since small-intestinal biopsies require invasive upper-endoscopy, and serology cannot predict CeD in an early stage or be used for monitoring disease after initiation of a gluten-free diet, the search for non-invasive biomarkers is ongoing. Here, we summarize current and up-and-coming non-invasive biomarkers that may be able to predict, diagnose, and monitor the progression of CeD. We further discuss how current and emerging techniques, such as (single-cell) transcriptomics and genomics, can be used to uncover the pathophysiology of CeD and identify non-invasive biomarkers.