RT Journal Article
T1 Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response
A1 Molina Jiménez, Francisca
A1 Ugalde Triviño, Lola
A1 Arias González, Laura
A1 Armenteros, Elisa
A1 Relaño Rupérez, Carlos
A1 Casabona, Sergio
A1 Moreno Monteagudo, José Andrés
A1 Pérez Fernández, María Teresa
A1 Martín Domínguez, Verónica
A1 Fernández Pacheco, Jennifer
A1 Laserna Mendieta, Emilio José
A1 Muñoz Hernández, Patricia
A1 García Martínez, Jorge
A1 Muñoz, Javier
A1 Lucendo, Alfredo J.
A1 Santander, Cecilio
A1 Majano Rodríguez, Pedro Lorenzo
AB BackgroundRecently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response.MethodsWe evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8‐week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non‐responders (non‐responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.ResultsComparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder‐PrePPI, non‐responder‐PrePPI, and non‐responder‐PostPPI) and without inflammation (controls and responder‐PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder‐PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder‐PrePPI and non‐responder‐PrePPI EoE patients before treatment.ConclusionThese findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.
PB Wiley
SN 0105-4538
YR 2024
FD 2024-08
LK https://hdl.handle.net/20.500.14352/112372
UL https://hdl.handle.net/20.500.14352/112372
LA eng
NO Molina-Jiménez F, Ugalde-Triviño L, Arias-González L, et al. Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response. Allergy. 2024;00:1-16. doi:10.1111/all.16261
NO Funding:PM and CS are supported by grants PI17/0008 and ISCIII-Proteored 2019 of Instituto de Salud Carlos III (ISCIII, Spain) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER). CS is also funded by Asociación Española de Gastroenterología (AEG) 2019 grant. JM is supported by grant PID2021-123144OB-I00 funded by MCIN /AEI /10.13039/501100011033 / FEDER, UE. LU-T is recipient of an INVESTIGO contract from Comunidad de Madrid (09-PIN1-00015.6/2022) partly funded by the European Social Fund, NextGenerationEU, and Recovery, Transformation and Resilience Plan. EA is recipient of an INVESTIGO contract from Ministry of Labour and Social Economy, the national public employment service (SEPE) (INVESTIGO Exp. 2022-C23.I01.P03. S0020-0000031.2) and CR-R is recipient of an INVESTIGO/ SEPE (Exp. 2022-C23.I01.P03. S0020-0000031) partly funded by the European Social Fund, NextGenerationEU, and Recovery, Transformation and Resilience Plan. EJL-M holds a Juan Rodés grant (JR19/00005) from the ISCIII, Spanish Ministry of Health—Social Services and Equality, which is partly funded by the European Social Fund (2014–2020).
NO European Commission
NO Ministerio de Ciencia e Innovación (España)
NO Ministerio de Trabajo y Economía Social (España)
NO Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
NO Servicio Público de Empleo Estatal (España)
NO Instituto de Salud Carlos III (España)
NO Asociación Española de Gastroenterología
NO Comunidad de Madrid
DS Docta Complutense
RD 17 abr 2025