The cellular response capacity (CRC) as a novel immunomonitoring approach in sepsis

David Alexander Christian Messerer; Paul Müller; Lisa Wohlgemuth; Frederik Münnich; Laura Stukan; Adam Omar Khalaf Mohamed; Jürgen Benjamin Hagemann; Alexander Sebastian Koller; Darko Jovanovski; Simon Lauer; Rebecca Traut; Leonard Schöbel; Bertram Dietrich Thomaß; Finn Münnich; Eberhard Barth; Manfred Weiss; Andreas Liebold; Bettina Jungwirth; Markus Huber-Lang

doi:10.1016/j.mmr.2026.100010

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The cellular response capacity (CRC) as a novel immunomonitoring approach in sepsis

RESEARCH | Updated：2026-05-11

- The cellular response capacity (CRC) as a novel immunomonitoring approach in sepsis
- Military Medical Research (2026)
- Affiliations：
  
  Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, 89081 Ulm, Germany
  Institute of Medical Microbiology and Hygiene, University Hospital Ulm, 89081 Ulm, Germany
  Institute for Transfusion Medicine, University Hospital Ulm, 89081 Ulm, Germany
  Clinic for Cardiothoracic and Vascular Surgery, University Hospital Ulm, 89081 Ulm, Germany
  Clinic for Anesthesiology and Intensive Care Medicine, University Hospital Ulm, 89081 Ulm, Germany
  Anesthesiology and Operative Intensive Care, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany
- Author bio：
  
  *David Alexander Christian Messerer, david.messerer@uni-ulm.de
- Funds：
- DOI：10.1016/j.mmr.2026.100010
  CLC：
- Received：18 August 2025，
  
  Revised：2026-03-05，
  
  Published：2026-03
- Accepted：
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Messerer DAC, Müller P, Wohlgemuth L, Münnich F, Stukan L, Mohamed AOK, et al. The cellular response capacity (CRC) as a novel immunomonitoring approach in sepsis. Mil Med Res. 2026;13(1):100010.
DOI：

Messerer DAC, Müller P, Wohlgemuth L, Münnich F, Stukan L, Mohamed AOK, et al. The cellular response capacity (CRC) as a novel immunomonitoring approach in sepsis. Mil Med Res. 2026;13(1):100010. DOI： 10.1016/j.mmr.2026.100010.

摘要

Abstract

Background:

Early recognition of sepsis remains difficult in clinical practice because conventional humoral biomarkers such as C-reactive protein

procalcitonin

and interleukin-6 (IL-6) exhibit unfavorable

slow-release kinetics and rise hours after the onset of infection. Flow cytometry enables upstream

cell-based immunomonitoring

but its clinical use is restricted by poor standardization of fluorescence measurements. In this study

the neutrophil cellular response capacity (CRC) was developed and evaluated as a standardized approach for rapid assessment of systemic inflammation in bacteremia and sepsis.

Methods:

The CRC is based on a flow cytometry-based framework that defines a stable maximal stimulation reference point for neutrophil granulocytes. The CRC was evaluated in a human

ex vivo

whole blood bacteremia model with graded exposure to

Escherichia coli

and compared with humoral inflammatory markers. Next

the CRC was assessed in a prospective intensive care unit seps

is cohort. Moreover

preliminary validation was performed in an independent sepsis cohort and in patients undergoing cardiac surgery.

Results:

In the bacteremia model

the CRC of neutrophil markers CD10

CD11b

and CD66b increased in a dose-dependent manner with increasing bacterial burden and detected inflammation at lower pathogen burdens than IL-6 and other humoral mediators

with a superior area under the receiver operating characteristic curve. In clinical sepsis

the CRC discriminated patients from age- and sex-matched healthy volunteers

with the CRC of CD11b showing the highest diagnostic performance. CRC values increased over time in patients with sepsis

consistent with immunological recovery. The maximal stimulation reference point for CD11b remained stable across inflammatory states

cohorts

and instruments. In addition

the CRC more precisely captured the onset and resolution of surgery-induced inflammation than conventional biomarkers.

Conclusions:

The CRC provides a rapid

standardized

and robust cell-based immunomonitoring tool that outperforms traditional humoral markers in experimental bacteremia and reliably identifies sepsis in clinical cohorts

strongly supporting its use as a novel biomarker for earlier

more precise sepsis diagnosis and monitoring.

关键词

Keywords

references

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