Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment

Front Immunol. 2024 Apr 5:15:1374611. doi: 10.3389/fimmu.2024.1374611. eCollection 2024.

Abstract

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response.

Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients.

Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI.

Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Keywords: biomarker; eosinophilic esophagitis; immunome; plasmacytoid dendritic cells; spectral cytometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers* / blood
  • Biopsy
  • Case-Control Studies
  • Dendritic Cells* / immunology
  • Eosinophilic Esophagitis* / blood
  • Eosinophilic Esophagitis* / diagnosis
  • Eosinophilic Esophagitis* / drug therapy
  • Eosinophilic Esophagitis* / immunology
  • Eosinophils / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proton Pump Inhibitors* / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Proton Pump Inhibitors
  • Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. 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. DB is funded through the Spanish Ministry of Science [PID2019-104218RB-I00], Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485) and the European Commission –NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform. 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. CR-R is recipient of an INVESTIGO contract from Ministry of Labor and Social Economy, the national public employment service (SEPE) (INVESTIGO Exp. 2022‐C23.I01.P03. S0020‐0000031) partly funded by the European Social Fund, NextGenerationEU, and Recovery, Transformation and Resilience Plan.