Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb;155(2):505-519.
doi: 10.1016/j.jaci.2024.09.016. Epub 2024 Sep 27.

Persistent desmoglein-1 downregulation and periostin accumulation in histologic remission of eosinophilic esophagitis

Hannes Hoelz  1 , Tim Faro  1 , Marie-Luise Frank  1 , Ignasi Forné  2 , Daniela Kugelmann  3 , Anja Jurk  1 , Simon Buehler  1 , Kolja Siebert  1 , Monica Matchado  4 , Tobias Straub  5 , Annett Hering  6 , Guido Piontek  7 , Susanna Mueller  7 , Sibylle Koletzko  8 , Markus List  9 , Katja Steiger  6 , Martina Rudelius  7 , Jens Waschke  3 , Tobias Schwerd  10
Affiliations
Free article

Persistent desmoglein-1 downregulation and periostin accumulation in histologic remission of eosinophilic esophagitis

Hannes Hoelz et al. J Allergy Clin Immunol. 2025 Feb.
Free article

Abstract

Background: Patients with eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite histologic remission.

Objective: We characterized persisting molecular alterations in pediatric patients with EoE using tissue transcriptomics and proteomics.

Methods: Esophageal biopsy samples (n = 247) collected prospectively during 189 endoscopies from pediatric patients with EoE (n = 36, up to 11 follow-up endoscopies) and pediatric controls (n = 44, single endoscopies) were subjected to bulk transcriptomics (n = 96) and proteomics (n = 151). Intercellular junctions (desmoglein-1/3, desmoplakin, E-cadherin) and epithelial-to-mesenchymal transition (vimentin:E-cadherin ratio) were assessed by immunofluorescence staining.

Results: Active EoE (≥15 eosinophils per high-power field [eos/hpf]), inactive EoE (<15 eos/hpf), and deep-remission EoE (0 eos/hpf) were diagnosed in 107 of 185, 78 of 185, and 41 of 185 biopsy samples, respectively. Among the dysregulated genes (up-/downregulated 310/112) and proteins (up-/downregulated 68/16) between active EoE and controls, 17 genes, and 6 proteins remained dysregulated in inactive EoE. Using persistently upregulated genes (n = 9) and proteins (n = 3) only, such as ALOX15, CXCL1, CXCL6, CTSG, CDH26, PRRX1, CLC, EPX, and periostin (POSTN), was sufficient to separate inactive EoE and deep-remission biopsy samples from control tissue. While 32 differentially expressed genes persisted in deep-remission EoE compared to controls, the proteome normalized except for persistently upregulated POSTN. Epithelial-to-mesenchymal transition normalized in inactive EoE, whereas desmosome recovery remained impaired as a result of desmoglein-1 downregulation.

Conclusion: The analysis of molecular changes shows persistent EoE-associated esophageal dysregulation despite histologic remission. These data expand our understanding of inflammatory processes and possible mechanisms that underlie tissue remodeling in EoE.

Keywords: Eosinophilic esophagitis; epithelial barrier dysfunction; fibrosis; proteome; transcriptome.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement Supported by “Förderprogramm für Forschung und Lehre (FöFoLe)” of the medical faculty, LMU Munich; and the German Research Foundation (DFG; SFB 1371-395357507). The funding source was not involved in the study design, collection, analysis, or interpretation of data or the preparation of the report and its publication. All data supporting our findings are available here and in the Online Repository. The mass spectrometry proteomics data were deposited to the ProteomeXchange Consortium via the PRIDE partner repository with dataset identifier PXD052250.48 (www.ebi.ac.uk/pride/archive/projects/PXD052250). Raw RNA sequencing data are available on reasonable request from the corresponding author. The data are protected and not publicly available because the research participants are children. Disclosure of potential conflict of interest: T. Schwerd reports receipt of received lecture honoraria from Nutricia and MSD, personal honorarium as member of an advisory board from AstraZeneca, and travel support from AbbVie and Ferring outside the submitted work. H. Hoelz reports receipt of lecture honoraria from Nutricia outside the submitted work. S. Koletzko reports receipt of fees as a member of advisory boards or as speaker from AbbVie, AstraZeneca, Danone, Janssen, Mead Johnson, Nestlé Nutrition, Pfizer, Sanofi, and Takeda outside the submitted work. M. List reports consulting for mbiomics GmbH. The rest of the authors declare that they have no relevant conflicts of interest.