Comprehensive proteomic characterization of the esophageal String Test identifies a luminal protein signature associated with eosinophilic esophagitis.
- 1Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain.
Abstract
BackgroundThe esophageal String Test (EST) is emerging as a minimally invasive alternative for assessing disease activity in eosinophilic esophagitis (EoE), yet the molecular composition of its protein content remains unknown.
ObjectiveTo comprehensively characterize the esophageal EST proteome, define an EoE-associated luminal protein signature, and evaluate its biological and clinical relevance.
MethodsEST samples were obtained from patients with active EoE, healthy controls (C) and patients with gastroesophageal reflux disease (GERD). Label-free proteomic profiling was performed by liquid chromatography-tandem mass spectrometry. Differential protein accumulation, principal component analysis (PCA), pathway annotation, comparison with published esophageal tissue and salivary proteomes, receiver operating characteristic (ROC) analyses and correlations with clinical disease activity were performed.
ResultsMore than 3,000 proteins were identified in esophageal EST samples. Global proteomic profiling clearly separated patients with EoE from both C and GERD, whereas only limited differences were observed between the latter two groups. This enabled the identification of an EoE-associated luminal protein signature comprising inflammatory, epithelial, and tissue remodeling proteins. Comparison with published proteomic datasets indicated that the EST samples a complex esophageal luminal protein microenvironment containing proteins represented in esophageal mucosa and saliva, together with inflammatory and extracellular components. Several individual proteins showed high discriminatory performance in this exploratory cohort for distinguishing EoE from non-EoE subjects, and multiple proteins correlated with eosinophil counts and endoscopic measures of disease activity.
ConclusionsThis study demonstrates that the EST provides access to a complex esophageal luminal protein microenvironment and establishes a molecular framework for its minimally invasive characterization in EoE.
Related
- Advances in Diagnostic Testing for Eosinophilic Esophagitis: Current Approaches, Limitations, and Emerging Technologies
- Lessons Learned: Digital Epidemiology of Eosinophilic Esophagitis and What Google Trends Reveals
- Two pediatric type II achalasia cases complicated by candidal and eosinophilic esophagitis: Successful peroral endoscopic myotomy treatment
- Herpes Simplex Esophagitis Superimposed on Eosinophilic Esophagitis in an Immunocompetent Patient.
- Eosinophilic Esophagitis and Marked Leukocytosis in Alpha-Gal Syndrome: Infection, Allergy, or Hematologic Malignancy?
BibTeX
@misc{delgadocruz2026comprehensive,
title = {{Comprehensive proteomic characterization of the esophageal String Test identifies a luminal protein signature associated with eosinophilic esophagitis.}},
author = {F. Delgado-Cruz and F. Molina-Jimenez and S. Casabona and E. Resina and V. Martin-Dominguez and J. Fernandez-Pacheco and L. Arias-Gonzalez and E. Armenteros and E. J. Laserna-Mendieta and P. Munoz-Hernandez and M. Sendino and J. Munoz and E. Efrem and A. J. Lucendo and P. Majano and C. Santander},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.26364161},
url = {https://www.medrxiv.org/content/10.64898/2026.09.30.26364161v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Comprehensive proteomic characterization of the esophageal String Test identifies a luminal protein signature associated with eosinophilic esophagitis.
AU - F. Delgado-Cruz
AU - F. Molina-Jimenez
AU - S. Casabona
AU - E. Resina
AU - V. Martin-Dominguez
AU - J. Fernandez-Pacheco
AU - L. Arias-Gonzalez
AU - E. Armenteros
AU - E. J. Laserna-Mendieta
AU - P. Munoz-Hernandez
AU - M. Sendino
AU - J. Munoz
AU - E. Efrem
AU - A. J. Lucendo
AU - P. Majano
AU - C. Santander
PY - 2026
DA - 2026/09/30
PB - medRxiv
DO - 10.64898/2026.09.30.26364161
UR - https://www.medrxiv.org/content/10.64898/2026.09.30.26364161v1
AB - BackgroundThe esophageal String Test (EST) is emerging as a minimally invasive alternative for assessing disease activity in eosinophilic esophagitis (EoE), yet the molecular composition of its protein content remains unknown. ObjectiveTo comprehensively characterize the esophageal EST proteome, define an EoE-associated luminal protein signature, and evaluate its biological and clinical relevance. MethodsEST samples were obtained from patients with active EoE, healthy controls (C) and patients with gastroesophageal reflux disease (GERD). Label-free proteomic profiling was performed by liquid chromatography-tandem mass spectrometry. Differential protein accumulation, principal component analysis (PCA), pathway annotation, comparison with published esophageal tissue and salivary proteomes, receiver operating characteristic (ROC) analyses and correlations with clinical disease activity were performed. ResultsMore than 3,000 proteins were identified in esophageal EST samples. Global proteomic profiling clearly separated patients with EoE from both C and GERD, whereas only limited differences were observed between the latter two groups. This enabled the identification of an EoE-associated luminal protein signature comprising inflammatory, epithelial, and tissue remodeling proteins. Comparison with published proteomic datasets indicated that the EST samples a complex esophageal luminal protein microenvironment containing proteins represented in esophageal mucosa and saliva, together with inflammatory and extracellular components. Several individual proteins showed high discriminatory performance in this exploratory cohort for distinguishing EoE from non-EoE subjects, and multiple proteins correlated with eosinophil counts and endoscopic measures of disease activity. ConclusionsThis study demonstrates that the EST provides access to a complex esophageal luminal protein microenvironment and establishes a molecular framework for its minimally invasive characterization in EoE.
ER -