High-dimensional flow cytometry identifies immune signatures associated with septic shock severity in critically ill postoperative patients - 08/10/26

Doi : 10.1016/j.accpm.2026.101898

Miguel Bardají-Carrillo ^a,^b,^c,^d,^e,^{^{1
These authors contributed equally.}}, Rosa Dolores Prieto-Utrera ^a,^f,^g,^{^{1
These authors contributed equally.}}, Rosa Cobo-Zubia ^a,^f,^g, Irina Rebollo-Mato ^a,^f,^g, Jessica Matesanz-Isabel ^a,^f,^g, María Álvarez-Bardón ^a,^c,^f,^g, Álvaro Tamayo-Velasco ^a,^e,^h,ⁱ, Marta Martin-Fernández ^a,^e,ⁱ, María Sherezade Tovar-Doncel ^a,^j, Peter Adamove ^k, Pedro Martínez-Paz ^a,^e,^f, Diego Fernández Sanchez-Gabriel ^a,^b, Fe Tomillo-Cebrian ^a,^b, Federico Bilotta ^l, Hugo Gonzalo-Benito ^a,^d,^e,^f,^g, Rocío López-Herrero ^a,^b,^c,^d,^e, Roberto Hornero ^m,ⁿ, Adrián García-Concejo ^a,^e,⁎ , David Bernardo ^e,^o, Rodrigo Poves-Álvarez ^a,^b,^c,^d,^e,^{^{1
These authors contributed equally.}}, Esther Gómez-Sánchez ^a,^b,^c,^d,^e,^{^{1
These authors contributed equally.}}, Eduardo Tamayo ^a,^b,^c,^d,^e,^{^{1
These authors contributed equally.}}

^a BioCritic, Group for Biomedical Research in Critical Care Medicine, 47003, Valladolid, Spain

^b Anesthesiology and Critical Care, Clinical University Hospital of Valladolid, Av. Ramón y Cajal, 3, 47003, Valladolid, Spain

^c Department of Surgery, University of Valladolid, 47003, Valladolid, Spain

^d Health Research Institute of Valladolid (IBioVALL), Valladolid, Spain

^e Biomedical Research Networking Center in Infectious Diseases (CIBERINFEC), Carlos III Health Institute, Madrid, Spain

^f Institute of Health Sciences of Castile and Leon (ICSCYL), Soria, Spain

^g Research Unit, University Clinical Hospital of Valladolid, Spain

^h Department of Hematology and Hemotherapy, University Clinical Hospital of Valladolid, 47003, Valladolid, Spain

ⁱ Department of Medicine, Toxicology and Dermatology, University of Valladolid, Valladolid, Spain

^j Anesthesiology and Critical Care, University Hospital of Toledo, Toledo, Spain

^k Department of Anesthesiology and Critical Care, Clinical Hospital of Bellvitge, Barcelona, 08907, Spain

^l "Sapienza" University of Rome, Department of Anesthesiology and Critical Care, Rome, Italy

^m Biomedical Engineering Group, University of Valladolid, Valladolid, Spain

ⁿ Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Carlos III Health Institute, Madrid, Spain

^o Mucosal Immunology Laboratory, Institute of Biomedicine and Molecular Genetics from Valladolid (IBGM, University of Valladolid - Spanish National Research Council). Valladolid, Spain

^⁎ Corresponding author.

Highlights

•	Septic shock is characterized by a distinct immune signature with depletion of dendritic cells and CD2 ⁻ /CD8 ⁺ NK-like cells.
•	High-dimensional spectral flow cytometry identifies immune cell alterations across non-septic ICU, sepsis, and septic shock patients.
•	A combined model integrating immune subsets with routine biomarkers (lactate and NLR) improves early prediction of septic shock.
•	Immune depletion signatures are externally validated by single-cell RNA sequencing, confirming systemic immune dysregulation.

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Abstract

Background

Sepsis and septic shock are associated with severe immune dysregulation and high mortality, while current biomarkers provide limited accuracy for early risk stratification. This study aimed to characterize immune cell alterations using high-dimensional spectral flow cytometry in postoperative ICU patients and to explore their association with disease severity in combination with clinical biomarkers.

Methods

We conducted a prospective multicentre study including 219 postoperative ICU patients classified as non-septic ICU (n = 77), sepsis (n = 62), and septic shock (n = 80). PBMCs were analysed by spectral flow cytometry. Immune populations were defined using supervised gating. Associations with clinical severity were assessed using logistic regression and ROC analysis. External validation was performed using single-cell RNA sequencing.

Results

Patients with septic shock showed a significant reduction in CD2 ⁻ /CD8 ⁺ NK-like cells and dendritic cells compared with sepsis and non-septic ICU patients. In multivariable models, lactate, neutrophil-to-lymphocyte ratio, dendritic cells, and NK-like cells were associated with septic shock. The combined model showed superior performance (AUC = 0.870). Single-cell RNA sequencing confirmed reduced dendritic and NK-like populations and revealed transcriptional alterations consistent with immune and metabolic dysregulation.

Conclusions

Septic shock is associated with a distinct immune signature characterized by reduced dendritic cells and NK-like cells. Integration of immune profiling with routine biomarkers is associated with improved discrimination of disease severity in this setting and supports further investigation of immune phenotyping approaches in sepsis.

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Keywords : Sepsis, Septic shock, Flow cytometry, Biomarkers.

Plan

Introduction

Material and methods

Study design and population

Ethical considerations and reporting standards

Clinical data and sample collection

Blood sampling timing

Statistical analysis and predictive modelling

External validation by scRNA-seq

Results

Patients’ characteristics

Identification and UMAP projection of the main immune subsets

Statistical analysis of immune subset distributions across clinical groups

Multivariate modeling and the relevance of immune subsets in clinical prediction of septic shock

Single-cell RNA sequencing validation of immune alterations associated with septic shock

Discussion

Authors’ contribution

Ethics approval

Funding

Data availability

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Vol 45 - N° 6

Article 101898- novembre 2026 Retour au numéro

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High-dimensional flow cytometry identifies immune signatures associated with septic shock severity in critically ill postoperative patients - 08/10/26

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