A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease

Celiac disease (CeD) is triggered by gluten and results in inflammation and villous atrophy of the small intestine. We aimed to explore the role of miRNA-mediated deregulation of the transcriptome in CeD. Duodenal biopsies of CeD patients (n = 33) and control subjects (n = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (n = 5) and CeD (n = 6). Differential expression analysis was performed to select CeD-associated miRNAs and genes. MiRNA‒target transcript pairs selected from public databases that also displayed a strong negative expression correlation in the current dataset (R < −0.7) were used to construct a CeD miRNA‒target transcript interaction network. The network includes 2030 miRNA‒target transcript interactions, including 423 experimentally validated pairs. Pathway analysis found that interactions are involved in immune-related pathways (e.g., interferon signaling) and metabolic pathways (e.g., lipid metabolism). The network includes 13 genes previously prioritized to be causally deregulated by CeD-associated genomic variants, including STAT1. CeD-associated miRNAs might play a role in promoting inflammation and decreasing lipid metabolism in the small intestine, thereby contributing unbalanced cell turnover in the intestinal crypt. Some CeD-associated miRNAs deregulate genes that are also affected by genomic CeD-risk variants, adding an additional layer of complexity to the deregulated transcriptome in CeD.

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Molecular Biomarkers for Celiac Disease: Past, Present and Future

International Journal of Molecular Sciences ◽

10.3390/ijms21228528 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8528

Author(s):

Aarón D. Ramírez-Sánchez ◽

Ineke L. Tan ◽

B.C. Gonera-de Jong ◽

Marijn C. Visschedijk ◽

Iris Jonkers ◽

...

Keyword(s):

Small Intestine ◽

Celiac Disease ◽

Early Stage ◽

Villous Atrophy ◽

Upper Endoscopy ◽

Gluten Free ◽

Non Invasive ◽

Immune Mediated ◽

Gastrointestinal Complaints ◽

Small Intestinal

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.

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Single cell transcriptome atlas of immune cells in human small intestine and in celiac disease

10.1101/721258 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nader Atlasy ◽

Anna Bujko ◽

Peter B Brazda ◽

Eva Janssen-Megens ◽

Espen S. Bækkevold ◽

...

Keyword(s):

T Cells ◽

Small Intestine ◽

Celiac Disease ◽

Single Cell ◽

Cd8 T Cells ◽

Immune Cells ◽

Current Knowledge ◽

Villous Atrophy ◽

Cellular Heterogeneity ◽

Human Small Intestine

Celiac disease (CeD) is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine1,2. The CeD lesion is characterized by crypt hyperplasia, villous atrophy and chronic inflammation with accumulation of leukocytes both in the lamina propria (LP) and in the epithelium3, which eventually leads to destruction of the intestinal epithelium1 and subsequent digestive complications and higher risk of non-hodgkin lymphoma4. A lifetime gluten-free diet is currently the only available treatment5. Gluten-specific LP CD4 T cells and cytotoxic intraepithelial CD8+ T cells are thought to be central in disease pathology1,6-8, however, CeD is a complex immune-mediated disorder and to date the findings are mostly based on analysis of heterogeneous cell populations and on animal models. Here, we comprehensively explore the cellular heterogeneity of CD45+ immune cells in human small intestine using index-sorting single-cell RNA-sequencing9,10. We find that myeloid and mast cell transcriptomes are reshaped in CeD. We observe extensive changes in the proportion and transcriptomes of CD4+ and CD8+ T cells and define a CD3zeta expressing NK-T-like cell population present in the control LP and epithelial layers that is absent and replaced in CeD. Our findings show that the immune landscape is dramatically changed in active CeD which provide new insights and considerably extend the current knowledge of CeD immunopathology.

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The Underlying Effects of Celiac Disease and Subsequent Implications on Deployment in the United States Army

Military Medicine ◽

10.1093/milmed/usab177 ◽

2021 ◽

Author(s):

Grayson Seidel ◽

Halle Kotchman ◽

Erin Milner ◽

Kevin J O’Donovan

Keyword(s):

Small Intestine ◽

Celiac Disease ◽

Villous Atrophy ◽

Gastrointestinal Symptoms ◽

Autoimmune Disorder ◽

The United States ◽

Service Members ◽

Diagnostic Process ◽

Intestinal Biopsy ◽

Gluten Free

ABSTRACT Introduction The purpose of this review is to provide an overview of the etiology, pathology, and treatments for celiac disease (CD), as well as to provide context as to how CD impacts the U.S. military. Materials and Methods To conduct this review, the authors surveyed recent epidemiology and immunology literature in order to provide a detailed summary of the current understanding of CD, its diagnosis, and the real-world impacts within the Department of Defense (DoD). Results We described the gluten proteins and both the immune response in CD. We further describe the underlying genetic risk factors and diagnosis and pathogenesis of the disease and conclude the review with a discussion of how current DoD regulations impact U.S. military readiness. Conclusion Celiac disease (CD) is an autoimmune disorder that results in damage to the small intestine. Ingestion of gluten in a CD patient is usually followed by villous atrophy in the small intestine, often along with other gastrointestinal symptoms. Around 1% of patients diagnosed with CD can experience complications if gluten-free diet is not followed, including intestinal lymphoma and hyposplenism. Therefore, a patient showing possible symptoms should discuss the diagnostic process with their healthcare providers to ensure adequate understanding of serological and genetic tests along with the histological examination of intestinal biopsy. Patients should seek consults with registered dietitians to structure their diets appropriately. Considering the prevalence and incidence of CD and gluten intolerances are increasing, the military should consider providing gluten-free Meals Ready-to-Eat as an option for all service members. Given the retention of service members with CD, subsequent admission of personnel with mild CD that does not affect the duties will allow the DoD access to a growing population of fully capable service members with critical technical skills who are eager to serve the USA.

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Identification of key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma

Current Bioinformatics ◽

10.2174/1574893615999200608125427 ◽

2020 ◽

Vol 15 ◽

Author(s):

Wei Han ◽

Dongchen Lu ◽

Chonggao Wang ◽

Mengdi Cui ◽

Kai Lu

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Differential Expression Analysis ◽

Interaction Network ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Integrated Analysis ◽

Papillary Thyroid ◽

Gene Set Enrichment ◽

Mirna Expression Data

Background: In the past decades, the incidence of thyroid cancer (TC) has been gradually increasing, owing to the widespread use of ultrasound scanning devices. However, the key mRNAs, miRNAs, and mRNA-miRNA network in papillary thyroid carcinoma (PTC) has not been fully understood. Material and Methods: In this study, multiple bioinformatics methods were employed, including differential expression analysis, gene set enrichment analysis, and miRNA-mRNA interaction network construction. Results: First, we investigated the key miRNAs that regulated significantly more differentially expressed genes based on GSEA method. Second, we searched for the key miRNAs based on the mRNA-miRNA interaction subnetwork involved in PTC. We identified hsa-mir-1275, hsa-mir-1291, hsa-mir-206 and hsa-mir-375 as the key miRNAs involved in PTC pathogenesis. Conclusion: The integrated analysis of the gene and miRNA expression data not only identified key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma, but also improved our understanding of the pathogenesis of PTC.

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Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211008709 ◽

2021 ◽

Vol 35 ◽

pp. 205873842110087

Author(s):

Taoufik Ben Houmich ◽

Brahim Admou

Keyword(s):

Celiac Disease ◽

Villous Atrophy ◽

Current Trend ◽

Diagnostic Delay ◽

General Medicine ◽

Iga Deficiency ◽

Health Concern ◽

Intestinal Biopsy ◽

Antibody Testing ◽

Main Challenge

Celiac disease (CD) is characterized by clinical polymorphism, with classic, asymptomatic or oligosymptomatic, and extra-intestinal forms, which may lead to diagnostic delay and exposure to serious complications. CD is a multidisciplinary health concern involving general medicine, pediatric, and adult gastroenterology, among other disciplines. Immunology and pathology laboratories have a fundamental role in diagnosing and monitoring CD. The diagnosis consists of serological testing based on IgA anti-transglutaminase (TG2) antibodies combined with IgA quantification to rule out IgA deficiency, a potential misleading factor of CD diagnosis. Positive TG2 serology should be corroborated by anti-endomysium antibody testing before considering an intestinal biopsy. Owing to multiple differential diagnoses, celiac disease cannot be confirmed based on serological positivity alone, nor on isolated villous atrophy. In children with classical signs or even when asymptomatic, with high levels of CD-linked markers and positive HLA DQ2 and/or DQ8 molecules, the current trend is to confirm the diagnosis on basis of the non-systematic use of the biopsy, which remains obligatory in adults. The main challenge in managing CD is the implementation and compliance with a gluten-free diet (GFD). This explains the key role of the dietitian and the active participation of patients and their families throughout the disease-management process. The presence of the gluten in several forms of medicine requires the sensitization of physicians when prescribing, and particularly when dispensing gluten-containing formulations by pharmacists. This underlines the importance of the contribution of the pharmacist in the care of patients with CD within the framework of close collaboration with physicians and nutritionists.

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Wait-and-See Approach or Gluten-Free Diet Administration—The Rational Management of Potential Coeliac Disease

Nutrients ◽

10.3390/nu13030947 ◽

2021 ◽

Vol 13 (3) ◽

pp. 947

Author(s):

Anna Szaflarska-Popławska

Keyword(s):

Small Intestine ◽

Celiac Disease ◽

Prognostic Factors ◽

Coeliac Disease ◽

Gluten Free Diet ◽

Gluten Free ◽

Individual Basis ◽

Therapeutic Decisions ◽

Rational Management ◽

Wait And See

Potential celiac disease (PCD) is a heterogeneous disease; only some patients develop full celiac disease (CD), characterised by advanced atrophic changes in the small intestine. Few accurate prognostic factors exist for the progression of PCD; therefore, therapeutic decisions should be made on an individual basis in each case. Patients with clinical gastroenterological or parenteral symptoms often benefit from a gluten-free diet, and those left on a diet containing gluten should receive clinical, serological and histopathological supervision.

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