Given the growing issue of bacterial multidrug resistance, it requires a rational basis ( 3). Sepsis is a leading cause of death globally ( 1), and timely administration of antibiotics is life-saving ( 2). Yet, the distinction of this process from noninfectious tissue injury-induced granulopoiesis remains to be investigated. 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. Blood counts of promyelocytes and myelocytes were higher in sepsis than in SIRS. 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.

Twelve of 30 validated genes, from 100 selected for changes in response to sepsis rather than SIRS, were endo-lysosomal. 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. Blood counts of granulocyte precursors were determined by flow cytometry in an extension of the validation cohort. Differential gene expression was validated by bead array in independent sepsis and SIRS patients (validation cohort). 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. CD15 + cells encompassing all stages of terminal granulocytic differentiation were analyzed. This study aimed to identify signature genes of blood granulocytes from patients with sepsis and SIRS on intensive care unit (ICU) admission. This process potentially contributes to blood gene classifiers of sepsis in systemic inflammatory response syndrome (SIRS) patients. 3Mannheim Institute of Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.2Next Generation Sequencing Core Facility, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.1Department of Anesthesiology and Surgical Intensive Care Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.Velásquez 1, Anna Coulibaly 1, Carsten Sticht 2, Jutta Schulte 1, Bianka Hahn 1, Timo Sturm 1, Roman Schefzik 1, Manfred Thiel 1,3 and Holger A.

Eliza ong jie zhi team asterisk