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Two New Neutrophil Subsets Define a Discriminating Sepsis Signature

Abstract : Rationale: Sepsis is the leading cause of death in adult ICUs. At present, sepsis diagnosis relies on nonspecific clinical features. It could transform clinical care to have immune-cell biomarkers that could predict sepsis diagnosis and guide treatment. For decades, neutrophil phenotypes have been studied in sepsis, but a diagnostic cell subset has yet to be identified. Objectives: To identify an early, specific immune signature of sepsis severity that does not overlap with other inflammatory biomarkers and that distinguishes patients with sepsis from those with noninfectious inflammatory syndrome. Methods: Mass cytometry combined with computational high-dimensional data analysis was used to measure 42 markers on whole-blood immune cells from patients with sepsis and control subjects and to automatically and comprehensively characterize circulating immune cells, which enables identification of novel, disease-specific cellular signatures. Measurements and Main Results: Unsupervised analysis of high-dimensional mass cytometry data characterized previously unappreciated heterogeneity within the CD64+ immature neutrophils and revealed two new subsets distinguished by CD123 and PD-L1 (programmed death ligand 1) expression. These immature neutrophils exhibited diminished activation and phagocytosis functions. The proportion of CD123-expressing neutrophils correlated with clinical severity. Conclusions: This study showed that these two new neutrophil subsets were specific to sepsis and detectable through routine flow cytometry by using seven markers. The demonstration here that a simple blood test distinguishes sepsis from other inflammatory conditions represents a key biological milestone that can be immediately translated into improvements in patient care.
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Submitted on : Wednesday, February 9, 2022 - 6:48:30 PM
Last modification on : Thursday, December 8, 2022 - 4:06:15 AM
Long-term archiving on: : Tuesday, May 10, 2022 - 7:21:02 PM


Meghraoui-Kheddar et al. - 202...
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Aïda Meghraoui-Kheddar, Benjamin Chousterman, Noëlline Guillou, Sierra Barone, Samuel Granjeaud, et al.. Two New Neutrophil Subsets Define a Discriminating Sepsis Signature. American Journal of Respiratory and Critical Care Medicine, 2022, 205 (1), pp.46-59. ⟨10.1164/rccm.202104-1027OC⟩. ⟨hal-03419725⟩



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