Ugalde-Triviño Lola, Molina-Jiménez Francisca, H-Vázquez Juan, Relaño-Rupérez Carlos, Arias-González Laura, Casabona Sergio, Pérez-Fernández María Teresa, Martín-Domínguez Verónica, Fernández-Pacheco Jennifer, Lucendo Alfredo J, Bernardo David, Santander Cecilio, Majano Pedro
Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain.
Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain.
Front Immunol. 2024 Apr 5;15:1374611. doi: 10.3389/fimmu.2024.1374611. eCollection 2024.
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.
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.
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.
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.
本研究旨在对嗜酸性粒细胞性食管炎(EoE)患者在质子泵抑制剂(PPI)治疗前后的循环免疫组进行特征分析,以确定治疗反应的潜在非侵入性生物标志物。
使用39通道光谱流式细胞术对19名健康对照者和24名EoE患者的外周血单核细胞(PBMC)进行研究。通过光谱流式细胞术分析和免疫荧光测定,对7名健康对照者和13名EoE患者食管活检中的浆细胞样树突状细胞(pDC)群体进行差异特征分析。
有趣的是,与对照组相比,基线时EoE患者的循环pDC水平较低。治疗前,对PPI治疗有反应的EoE患者的循环pDC和经典单核细胞水平高于无反应者。此外,PPI治疗后,所有EoE患者的pDC水平均升高,而仅在对PPI有反应的患者中恢复到正常水平。最后,循环pDC水平与食管活检中的嗜酸性粒细胞峰值计数和pDC计数呈负相关。在活动性EoE期间,组织pDC数量显著增加,与PPI治疗前有反应的患者相比,无反应患者的组织pDC数量更高。摄入PPI后pDC水平下降,在PPI治疗后有反应的患者中进一步恢复至几乎对照水平。
我们在此描述了EoE患者诊断时独特的免疫特征。此外,循环pDC也可作为一种新型非侵入性生物标志物,用于预测随后对PPI治疗的反应。