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Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis

Background: Eosinophilic esophagitis (EoE) is commonly associated with concomitant atopic diseases including atopic dermatitis (AD) and allergic airway (AA) diseases including asthma. Despite this link and the shared pathologic features across these three disorders, detailed analyses of the unifying...

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Autores principales: Doucet-Ladevèze, Rémi, Holvoet, Sébastien, Raymond, Frédéric, Foata, Francis, Hershey, Gurjit K. Khurana, Sherrill, Joseph D., Rothenberg, Marc E., Blanchard, Carine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879454/
https://www.ncbi.nlm.nih.gov/pubmed/31824894
http://dx.doi.org/10.3389/fped.2019.00467
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author Doucet-Ladevèze, Rémi
Holvoet, Sébastien
Raymond, Frédéric
Foata, Francis
Hershey, Gurjit K. Khurana
Sherrill, Joseph D.
Rothenberg, Marc E.
Blanchard, Carine
author_facet Doucet-Ladevèze, Rémi
Holvoet, Sébastien
Raymond, Frédéric
Foata, Francis
Hershey, Gurjit K. Khurana
Sherrill, Joseph D.
Rothenberg, Marc E.
Blanchard, Carine
author_sort Doucet-Ladevèze, Rémi
collection PubMed
description Background: Eosinophilic esophagitis (EoE) is commonly associated with concomitant atopic diseases including atopic dermatitis (AD) and allergic airway (AA) diseases including asthma. Despite this link and the shared pathologic features across these three disorders, detailed analyses of the unifying molecular pathways are lacking. Objectives: We sought to investigate the mRNA expression profile overlap between EoE, AA, and AD and to identify the involvement of interleukin 13 (IL-13) in modulating gene expression. Methods: Whole-genome mRNA expression analyses were performed on tissue specimens (biopsies or nasal brushes) from patients with EoE, AD, and AA, and IL-13-stimulated primary human epithelial cells from the esophagus, the skin, and the airways. Results: By human disease expression profiles, EoE evidenced a significantly higher overlap (p = 0.0006) with AD (181 transcripts; 10%) than with AA (124 transcripts, 7%). Only 18 genes were found to be commonly dysregulated among the three diseases; these included filaggrin, histamine receptor H1, claudin 1, cathepsin C, plasminogen activator urokinase receptor, and suppressor of cytokine signaling 3. Ontogenetic analysis revealed a common immune/inflammatory response among the three diseases and a different epithelial response (epidermal cell differentiation) between EoE and AA. The overlap between the IL-13–stimulated epithelial cell transcriptome and the respective disease transcriptome was 22, 9, and 5% in EoE, AD, and AA, respectively, indicating a greater involvement of the IL-13 pathway in EoE than AA (p = 0.0007) or AD (p = 0.02). Conclusion: EoE, AD, and AA share a common set of disease-specific transcripts, highlighting common molecular etiology. Their comparative analysis indicates relatively closer relationships between EoE and AD, particularly centered around IL-13–driven pathways. Therefore, these findings provide an increased rationale for shared therapeutic strategies.
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spelling pubmed-68794542019-12-10 Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis Doucet-Ladevèze, Rémi Holvoet, Sébastien Raymond, Frédéric Foata, Francis Hershey, Gurjit K. Khurana Sherrill, Joseph D. Rothenberg, Marc E. Blanchard, Carine Front Pediatr Pediatrics Background: Eosinophilic esophagitis (EoE) is commonly associated with concomitant atopic diseases including atopic dermatitis (AD) and allergic airway (AA) diseases including asthma. Despite this link and the shared pathologic features across these three disorders, detailed analyses of the unifying molecular pathways are lacking. Objectives: We sought to investigate the mRNA expression profile overlap between EoE, AA, and AD and to identify the involvement of interleukin 13 (IL-13) in modulating gene expression. Methods: Whole-genome mRNA expression analyses were performed on tissue specimens (biopsies or nasal brushes) from patients with EoE, AD, and AA, and IL-13-stimulated primary human epithelial cells from the esophagus, the skin, and the airways. Results: By human disease expression profiles, EoE evidenced a significantly higher overlap (p = 0.0006) with AD (181 transcripts; 10%) than with AA (124 transcripts, 7%). Only 18 genes were found to be commonly dysregulated among the three diseases; these included filaggrin, histamine receptor H1, claudin 1, cathepsin C, plasminogen activator urokinase receptor, and suppressor of cytokine signaling 3. Ontogenetic analysis revealed a common immune/inflammatory response among the three diseases and a different epithelial response (epidermal cell differentiation) between EoE and AA. The overlap between the IL-13–stimulated epithelial cell transcriptome and the respective disease transcriptome was 22, 9, and 5% in EoE, AD, and AA, respectively, indicating a greater involvement of the IL-13 pathway in EoE than AA (p = 0.0007) or AD (p = 0.02). Conclusion: EoE, AD, and AA share a common set of disease-specific transcripts, highlighting common molecular etiology. Their comparative analysis indicates relatively closer relationships between EoE and AD, particularly centered around IL-13–driven pathways. Therefore, these findings provide an increased rationale for shared therapeutic strategies. Frontiers Media S.A. 2019-11-20 /pmc/articles/PMC6879454/ /pubmed/31824894 http://dx.doi.org/10.3389/fped.2019.00467 Text en Copyright © 2019 Doucet-Ladevèze, Holvoet, Raymond, Foata, Hershey, Sherrill, Rothenberg and Blanchard. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Doucet-Ladevèze, Rémi
Holvoet, Sébastien
Raymond, Frédéric
Foata, Francis
Hershey, Gurjit K. Khurana
Sherrill, Joseph D.
Rothenberg, Marc E.
Blanchard, Carine
Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis
title Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis
title_full Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis
title_fullStr Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis
title_full_unstemmed Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis
title_short Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis
title_sort transcriptomic analysis links eosinophilic esophagitis and atopic dermatitis
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879454/
https://www.ncbi.nlm.nih.gov/pubmed/31824894
http://dx.doi.org/10.3389/fped.2019.00467
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