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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pediatr. | doi: 10.3389/fped.2019.00467

Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis

Rémi Doucet-Ladevèze1,  Sebastien Holvoet1,  Frederic Raymond,1, Francis Foata1, Gurjit (Neeru) Khurana2, Joseph Sherrill2, Marc Rothenberg2 and  Carine Blanchard1*
  • 1Nestlé Research Center, Switzerland
  • 2Cincinnati Children's Hospital Medical Center, United States

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 3 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 = 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.

Keywords: Asthma, Atopic dermatitis (AD), Eosinophilic Esophagitis, Epithelial Cells, Interleukin 13 (IL-13)

Received: 16 Aug 2019; Accepted: 28 Oct 2019.

Copyright: © 2019 Doucet-Ladevèze, Holvoet, Raymond,, Foata, Khurana, Sherrill, Rothenberg and Blanchard. 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.

* Correspondence: Dr. Carine Blanchard, Nestlé Research Center, Lausanne, 1000, Vaud, Switzerland,