학술논문
The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsisResearch in context
Document Type
article
Author
Roberto Lozano-Rodríguez; José Avendaño-Ortíz; Karla Montalbán-Hernández; Juan Carlos Ruiz-Rodríguez; Ricardo Ferrer; Alejandro Martín-Quirós; Charbel Maroun-Eid; Juan José González-López; Anna Fàbrega; Verónica Terrón-Arcos; María Gutiérrez-Fernández; Elisa Alonso-López; Carolina Cubillos-Zapata; María Fernández-Velasco; Rebeca Pérez de Diego; Pablo Pelegrin; Carlos García-Palenciano; Francisco J. Cueto; Carlos del Fresno; Eduardo López-Collazo
Source
EBioMedicine, Vol 97, Iss , Pp 104841- (2023)
Subject
Language
English
ISSN
2352-3964
Abstract
Summary: Background: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. Methods: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). Findings: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656–0.769; p