X-ray microtomography imaging enables accurate visualization and quantification of the small-intestinal villi microvasculature - celiac disease as a model.

Vasculature of the small bowel mucosa, with a significant role in nutrient absorption and gut homeostasis, has been suggested to undergo remodeling in various gastrointestinal disorders, including celiac disease. However, due to its spatial organization within the mucosa, conventional 2D histological methods are of limited value in studying the intestinal vasculature reliably. X-ray microtomography (micro-CT) is a promising tool for soft tissue imaging, as it enables digital 3D reconstruction of various tissue samples, including endoscopically obtained small-bowel mucosal biopsies.

Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.

Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study.

Indirect Markers of Intestinal Damage in IgA Nephropathy.

Introduction: Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN.

Coeliac disease: what can we learn from prospective studies about disease risk?

Paediatric prospective studies of coeliac disease with longitudinal collection of biological samples and clinical data offer a unique perspective on disease risk. This Review highlights the information now available from international paediatric prospective studies on genetic and environmental risk factors for coeliac disease. In addition, recent omics studies have made it possible to study complex interactions between genetic and environmental factors and thereby further our insight into the causes of the disease.

Prevalence of vomiting and nausea and associated factors after chronic and acute gluten exposure in celiac disease.

Background: Vomiting and nausea seem to be relatively specific symptoms related to gluten ingestion in treated celiac disease. However, the overall prevalence and associated factors of these symptoms after chronic gluten exposure at celiac disease diagnosis and acute re-exposure during gluten challenge remain obscure.

Methods: Medical data on 815 adult celiac disease patients were collected at diagnosis from the medical records and through supplementary interviews.

Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes.

Gluten-free diet adherence in children with screening-detected celiac disease using a prospective birth cohort study.

Background: Celiac disease has an increasing incidence worldwide and is treated with lifelong adherence to a gluten-free diet. We aimed to describe gluten-free diet adherence rates in children with screening-identified celiac disease, determine adherence-related factors, and compare adherence to food records in a multinational prospective birth cohort study.

Methods: Children in The Environmental Determinants of Diabetes in the Young study with celiac disease were included.

Incidence of Pediatric Celiac Disease Varies by Region.

Introduction: The Environmental Determinants of Diabetes in the Young study follows an HLA risk selected birth cohort for celiac disease (CD) development using a uniform protocol. Children under investigation come from 6 different regions within Europe and the United States. Our aim was to identify regional differences in CD autoimmunity and CD cumulative incidence for children born between 2004 and 2010.

Validation of the X-ray microtomography in the assessment of duodenal morphometry and surface area in celiac disease.

Background: Duodenal histology remains the diagnostic reference standard in celiac disease. However, traditional methods have suboptimal sensitivity and reproducibility for early mucosal changes and research purposes. We validated a recently introduced micro-CT imaging method for an accurate digital evaluation of duodenal histomorphometry and mucosal surface areas.

Coeliac disease re-screening among once seronegative at-risk relatives: A long-term follow-up study.

Background: Serological screening of the relatives of coeliac disease patients is widely endorsed. However, the need for and the optimal timing of possible re-testing of once seronegative at-risk individuals for coeliac disease remain unclear.

Objective: We investigated this issue by inviting a large cohort of previously screening-negative relatives of patients with coeliac disease to participate in a follow-up study.

Antibody Responses to Transglutaminase 3 in Dermatitis Herpetiformis: Lessons from Celiac Disease.

Dermatitis herpetiformis (DH) is the skin manifestation of celiac disease, presenting with a blistering rash typically on the knees, elbows, buttocks and scalp. In both DH and celiac disease, exposure to dietary gluten triggers a cascade of events resulting in the production of autoantibodies against the transglutaminase (TG) enzyme, mainly TG2 but often also TG3. The latter is considered to be the primary autoantigen in DH.

Toward Xeno-Free Differentiation of Human Induced Pluripotent Stem Cell-Derived Small Intestinal Epithelial Cells.

The small intestinal epithelium has an important role in nutrition, but also in drug absorption and metabolism. There are a few two-dimensional (2D) patient-derived induced pluripotent stem cell (iPSC)-based intestinal models enabling easy evaluation of transcellular transport. It is known that animal-derived components induce variation in the experimental outcomes.

Dissecting the contribution of single nucleotide polymorphisms in and genomic regions to the celiac disease phenotype.

Purpose And Objectives: Given their role in homing immune cells to the intestine, CC motif chemokine receptor 9 (CCR9) and its specific ligand CC motif chemokine ligand 25 (CCL25) are interesting candidate genes for celiac disease. These genes are located in regions previously shown to be associated with or linked to celiac disease, but no investigations on their association with various celiac disease phenotypes have so far been conducted. Here we studied such associations of both genotyped and imputed single nucleotide polymorphisms (SNPs) with either regulatory function or exonic location of the and loci.

Presence of high-risk HLA genotype is the most important individual risk factor for coeliac disease among at-risk relatives.

Background: Family screening has been advocated as a means to reduce the major underdiagnosis of coeliac disease. However, the precise risk of the disease in relatives and the impact of patient- and relative-related individual factors remain obscure.

Aims: To investigate the individual risk of coeliac disease among patients' relatives.

Celiac Disease-Type Tissue Transglutaminase Autoantibody Deposits in Kidney Biopsies of Patients with IgA Nephropathy.

An association between celiac disease and IgA nephropathy (IgAN) has been suggested. In celiac disease, in addition to circulating in serum, IgA-class tissue transglutaminase (tTG) autoantibodies are deposited in the small bowel mucosa and extraintestinal organs. In this case series of IgAN patients with or without celiac disease, we studied whether celiac disease-type IgA-tTG deposits occur in kidney biopsies.

Missing Insight Into T and B Cell Responses in Dermatitis Herpetiformis.

Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation.

Iron Transporter Protein Expressions in Children with Celiac Disease.

Anemia is a frequent finding in children with celiac disease but the detailed pathophysiological mechanisms in the intestine remain obscure. One possible explanation could be an abnormal expression of duodenal iron transport proteins. However, the results have so far been inconsistent.

Independent and cumulative coeliac disease-susceptibility loci are associated with distinct disease phenotypes.

The phenotype of coeliac disease varies considerably for incompletely understood reasons. We investigated whether established coeliac disease susceptibility variants (SNPs) are individually or cumulatively associated with distinct phenotypes. We also tested whether a polygenic risk score (PRS) based on genome-wide associated (GWA) data could explain the phenotypic variation.

Influence of HLA-DQ2.5 Dose on Clinical Picture of Unrelated Celiac Disease Patients.

The clinical phenotype of celiac disease varies considerably among patients and the dosage of HLA-DQ2.5 alleles has been suggested to be a contributing factor. We investigated whether HLA-DQ2.

Current and emerging therapies for coeliac disease.

Coeliac disease is a common enteropathy that occurs in genetically susceptible individuals in response to the ingestion of gluten proteins present in wheat, rye and barley. Currently, the only available treatment for the condition is a strict, life-long gluten-free diet that, despite being safe and often effective, is associated with several challenges. Due to the high cost, particularly restrictive nature and perception of decreased quality of life associated with the diet, some patients are continuously exposed to gluten, which prevents an adequate disease control.

The use of peripheral blood mononuclear cells in celiac disease diagnosis and treatment.

: Celiac disease is characterized by an abnormal immune activation driven by the ingestion of gluten from wheat, barley, and rye. Gluten-specific CD4 T cells play an important role in disease pathogenesis and are detectable among peripheral blood mononuclear cells (PBMCs). : This review summarizes the use of celiac disease patient PBMCs in clinical applications focusing on their exploitation in the development of diagnostic approaches and novel drugs to replace or complement gluten-free diet.

Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities.

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities.

X-ray microtomography is a novel method for accurate evaluation of small-bowel mucosal morphology and surface area.

The often poorly orientated small-bowel mucosal biopsies taken for the diagnostics of celiac disease and other intestinal disorders are prone to misinterpretation. Furthermore, conventional histopathology has suboptimal sensitivity for early histopathological changes observed in short-term challenge studies. X-ray microtomography (micro-CT) is a promising new method for accurate imaging of human-derived biological samples.