Key signature genes of early terminal granulocytic differentiation distinguish sepsis from systemic inflammatory response syndrome on intensive care unit admission

• Verfasst von: Velásquez, Sonia Y. [VerfasserIn]
• Verfasst von: Coulibaly, Anna [VerfasserIn]
• Verfasst von: Sticht, Carsten [VerfasserIn]
• Verfasst von: Schulte, Jutta [VerfasserIn]
• Verfasst von: Hahn, Bianka [VerfasserIn]
• Verfasst von: Sturm, Timo [VerfasserIn]
• Verfasst von: Schefzik, Roman [VerfasserIn]
• Verfasst von: Thiel, Manfred [VerfasserIn]
• Verfasst von: Lindner, Holger A. [VerfasserIn]
• Titel: Key signature genes of early terminal granulocytic differentiation distinguish sepsis from systemic inflammatory response syndrome on intensive care unit admission
• Verf.angabe: Sonia Y. Velásquez, Anna Coulibaly, Carsten Sticht, Jutta Schulte, Bianka Hahn, Timo Sturm, Roman Schefzik, Manfred Thiel and Holger A. Lindner
• E-Jahr: 2022
• Jahr: 30 June 2022
• Umfang: 14 S.
• Fussnoten: Gesehen am 12.07.2022
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2022
• Band/Heft Quelle: 13(2022), Artikel-ID 864835, Seite 1-14
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2022.864835
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Forschungsdaten: Lindner, Holger A., 1970 - : Key signature genes of early terminal granulocytic differentiation distinguish sepsis from SIRS on ICU admission
• K10plus-PPN: 1809918960
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Infection can induce granulopoiesis. This process potentially contributes to blood gene classifiers of sepsis in systemic inflammatory response syndrome (SIRS) patients. This study aimed to identify signature genes of blood granulocytes from patients with sepsis and SIRS on intensive care unit (ICU) admission. CD15+ cells encompassing all stages of terminal granulocytic differentiation were analyzed. CD15 transcriptomes from patients with sepsis and SIRS on ICU admission and presurgical controls (discovery cohort) were subjected to differential gene expression and pathway enrichment analyses. Differential gene expression was validated by bead array in independent sepsis and SIRS patients (validation cohort). Blood counts of granulocyte precursors were determined by flow cytometry in an extension of the validation cohort. Despite similar transcriptional CD15 responses in sepsis and SIRS, enrichment of canonical pathways known to decline at the metamyelocyte stage (mitochondrial, lysosome, cell cycle, and proteasome) was associated with sepsis but not SIRS. Twelve of 30 validated genes, from 100 selected for changes in response to sepsis rather than SIRS, were endo-lysosomal. Revisiting the discovery transcriptomes revealed an elevated expression of promyelocyte-restricted azurophilic granule genes in sepsis and myelocyte-restricted specific granule genes in sepsis followed by SIRS. Blood counts of promyelocytes and myelocytes were higher in sepsis than in SIRS. Sepsis-induced granulopoiesis and signature genes of early terminal granulocytic differentiation thus provide a rationale for classifiers of sepsis in patients with SIRS on ICU admission. Yet, the distinction of this process from noninfectious tissue injury-induced granulopoiesis remains to be investigated.