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

Abstract

ABSTRACTObjectivesThe 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.MethodsPBMCs 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 of immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients.ResultsInterestingly, 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.ConclusionsWe 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.WHAT IS KNOWNEosinophilic esophagitis (EoE) is a Th2 type immune disorder with increased prevalence in the last years.Proton pump inhibitor (PPI) treatment is the preferred first-line therapy for EoE, which leads to clinical and pathological reversion in about half of the cases. Non-responding patients require other therapeutic options.Currently, an endoscopy with esophageal biopsies is required for EoE diagnosis and to monitor response to treatment. Therefore, the discovery of non-invasive biomarkers is of utmost importance for treatment monitoring.To date only peripheral eosinophil and Th2 profiles have been studied in EoE.WHAT IS NEW HEREAt diagnosis EoE patients have a specific circulating immune signature.PPI-responding and non-responding EoE patients have different immune fingerprints at baseline.Immune characterization of EoE patients at diagnosis and after PPI treatment unveiled differential levels of circulating plasmacytoid dendritic cells (pDCs) depending on their inflammatory state and response to PPI treatment. Those levels are related with the number of pDCs infiltrated in the esophageal tissue.