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| Pàgina inicial > Articles > Articles publicats > The prognostic impact of SIGLEC5-induced impairment of CD8 + T cell activation in sepsis |
(Universitat Autònoma de Barcelona. Departament de Medicina) (Universitat Autònoma de Barcelona. Departament de Medicina) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Hospital Universitari Vall d'Hebron) (Hospital Universitario La Paz (Madrid)) (Hospital Universitario Virgen de la Arrixaca (Múrcia))| Data: | 2023 |
| Resum: | 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. 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). 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 < 0. 0001). Kaplan-Meier survival curve showed a significant decrease in survival above the calculated cut-off (HR of 3. 418, 95% CI, 2. 380-4. 907, p < 0. 0001 by log-rank test) estimated by Youden Index (523. 6 ng/mL). SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. |
| Ajuts: | Ministerio de Economía y Competitividad PIE15/00065 Instituto de Salud Carlos III PI18/00148 Ministerio de Economía y Competitividad PI14/01234 Instituto de Salud Carlos III PI21/00869 Instituto de Salud Carlos III PI21/01178 Instituto de Salud Carlos III FI19/00334 Instituto de Salud Carlos III CD21/00059 European Commission 713673 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Sepsis ; Immune checkpoint ; SIGLEC5 ; T-cell exhaustion ; Biomarker ; HIF1α |
| Publicat a: | EBioMedicine, Vol. 97 (November 2023) , art. 104841, ISSN 2352-3964 |
