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RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis
BACKGROUND & AIMS: The early steps in the pathophysiology of celiac disease (CD) leading to loss of tolerance to gluten are poorly described. Our aim was to use RNA sequencing of duodenal biopsies in patients with active CD, CD in remission, and non-CD controls to gain insight into CD pathophysi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472737/ https://www.ncbi.nlm.nih.gov/pubmed/30998704 http://dx.doi.org/10.1371/journal.pone.0215132 |
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author | Leonard, Maureen M. Bai, Yu Serena, Gloria Nickerson, Kourtney P. Camhi, Stephanie Sturgeon, Craig Yan, Shu Fiorentino, Maria R. Katz, Aubrey Nath, Barbara Richter, James Sleeman, Matthew Gurer, Cagan Fasano, Alessio |
author_facet | Leonard, Maureen M. Bai, Yu Serena, Gloria Nickerson, Kourtney P. Camhi, Stephanie Sturgeon, Craig Yan, Shu Fiorentino, Maria R. Katz, Aubrey Nath, Barbara Richter, James Sleeman, Matthew Gurer, Cagan Fasano, Alessio |
author_sort | Leonard, Maureen M. |
collection | PubMed |
description | BACKGROUND & AIMS: The early steps in the pathophysiology of celiac disease (CD) leading to loss of tolerance to gluten are poorly described. Our aim was to use RNA sequencing of duodenal biopsies in patients with active CD, CD in remission, and non-CD controls to gain insight into CD pathophysiology, identify additional genetic signatures linked to CD, and possibly uncover targets for future therapeutic agents. METHODS: We performed whole transcriptome shotgun sequencing of intestinal biopsies in subjects with active and remission CD and non-CD controls. We also performed functional pathway analysis of differentially expressed genes to identify statistically significant pathways that are up or down regulated in subjects with active CD compared to remission CD. RESULTS: We identified the upregulation of novel genes including IL12R, ITGAM and IGSF4 involved in the immune response machinery and cell adhesion process in the mucosa of subjects with active CD compared to those in remission. We identified a unique signature of genes, related to innate immunity, perturbed exclusively in CD irrespective of disease status. Finally, we highlight novel pathways of interest that may contribute to the early steps of CD pathogenesis and its comorbidities such as the spliceosome, pathways related to the innate immune response, and pathways related to autoimmunity. CONCLUSIONS: Our study confirmed previous findings based on GWAS and immunological studies pertinent to CD pathogenesis and describes novel genes and pathways that with further validation may be found to contribute to the early steps in the pathogenesis of CD, ongoing inflammation, and comorbidities associated with CD. |
format | Online Article Text |
id | pubmed-6472737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64727372019-05-03 RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis Leonard, Maureen M. Bai, Yu Serena, Gloria Nickerson, Kourtney P. Camhi, Stephanie Sturgeon, Craig Yan, Shu Fiorentino, Maria R. Katz, Aubrey Nath, Barbara Richter, James Sleeman, Matthew Gurer, Cagan Fasano, Alessio PLoS One Research Article BACKGROUND & AIMS: The early steps in the pathophysiology of celiac disease (CD) leading to loss of tolerance to gluten are poorly described. Our aim was to use RNA sequencing of duodenal biopsies in patients with active CD, CD in remission, and non-CD controls to gain insight into CD pathophysiology, identify additional genetic signatures linked to CD, and possibly uncover targets for future therapeutic agents. METHODS: We performed whole transcriptome shotgun sequencing of intestinal biopsies in subjects with active and remission CD and non-CD controls. We also performed functional pathway analysis of differentially expressed genes to identify statistically significant pathways that are up or down regulated in subjects with active CD compared to remission CD. RESULTS: We identified the upregulation of novel genes including IL12R, ITGAM and IGSF4 involved in the immune response machinery and cell adhesion process in the mucosa of subjects with active CD compared to those in remission. We identified a unique signature of genes, related to innate immunity, perturbed exclusively in CD irrespective of disease status. Finally, we highlight novel pathways of interest that may contribute to the early steps of CD pathogenesis and its comorbidities such as the spliceosome, pathways related to the innate immune response, and pathways related to autoimmunity. CONCLUSIONS: Our study confirmed previous findings based on GWAS and immunological studies pertinent to CD pathogenesis and describes novel genes and pathways that with further validation may be found to contribute to the early steps in the pathogenesis of CD, ongoing inflammation, and comorbidities associated with CD. Public Library of Science 2019-04-18 /pmc/articles/PMC6472737/ /pubmed/30998704 http://dx.doi.org/10.1371/journal.pone.0215132 Text en © 2019 Leonard et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Leonard, Maureen M. Bai, Yu Serena, Gloria Nickerson, Kourtney P. Camhi, Stephanie Sturgeon, Craig Yan, Shu Fiorentino, Maria R. Katz, Aubrey Nath, Barbara Richter, James Sleeman, Matthew Gurer, Cagan Fasano, Alessio RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
title | RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
title_full | RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
title_fullStr | RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
title_full_unstemmed | RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
title_short | RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
title_sort | rna sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472737/ https://www.ncbi.nlm.nih.gov/pubmed/30998704 http://dx.doi.org/10.1371/journal.pone.0215132 |
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