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Purpose <p>Septic patients simultaneously experience hyperinflammation and immunosuppression, the latter driving ICU-acquired infections, prolonged stays in ICU, and increased mortality. As immunostimulant therapies enter clinical trials, effective stratification is critical to identify patients with the most profound immune dysfunction. Monocyte HLA-DR expression (mHLA-DR) has emerged as the most reliable and actionable biomarker of sepsis-induced immunosuppression.</p> Methods <p>We conducted a real-world, 20-year cohort study of 1023 septic shock patients, measuring mHLA-DR by standardized flow cytometry during the first week of ICU admission. Primary outcomes included day-28 and day-90 mortality, and ICU-acquired infections.</p> Results <p>Low mHLA-DR (&lt; 8000 AB/C, a threshold already used in phase II trials) was significantly associated with increased mortality and ICU-acquired infections. This association held across static and dynamic measures, multivariate analyses, Kaplan–Meier survival curves, and trajectory clustering (<i>K</i>-means).</p> Conclusions <p>This large real-world study confirms that mHLA-DR is a robust enrichment biomarker for identifying the most immunosuppressed septic shock patients at higher risk of adverse outcomes. Importantly, time-course analysis suggests that early immune downregulation may represent a physiological adaptation, while delayed and persistent immunosuppression is associated with worse outcomes. Early single time-point measurements may fail to identify patients who are unlikely to develop delayed immunosuppression. Tracking mHLA-DR trajectories after the initial ICU days is essential for detecting persistent immune dysfunction and selecting patients in case of immunostimulant approaches.</p>

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Monocyte HLA-DR expression in septic shock patients: insights from a 20-year real-world cohort of 1023 cases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月23日

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  • Guillaume Monneret,
  • Thomas Lafon,
  • Morgane Gossez,
  • Bruno Evrard,
  • Maxime Bodinier,
  • Thomas Rimmelé,
  • Laurent Argaud,
  • Martin Cour,
  • Arnaud Friggeri,
  • Alain Lepape,
  • Bernard Allaouchiche,
  • Anne-Claire Lukaszewicz,
  • Fabienne Venet

摘要

Purpose

Septic patients simultaneously experience hyperinflammation and immunosuppression, the latter driving ICU-acquired infections, prolonged stays in ICU, and increased mortality. As immunostimulant therapies enter clinical trials, effective stratification is critical to identify patients with the most profound immune dysfunction. Monocyte HLA-DR expression (mHLA-DR) has emerged as the most reliable and actionable biomarker of sepsis-induced immunosuppression.

Methods

We conducted a real-world, 20-year cohort study of 1023 septic shock patients, measuring mHLA-DR by standardized flow cytometry during the first week of ICU admission. Primary outcomes included day-28 and day-90 mortality, and ICU-acquired infections.

Results

Low mHLA-DR (< 8000 AB/C, a threshold already used in phase II trials) was significantly associated with increased mortality and ICU-acquired infections. This association held across static and dynamic measures, multivariate analyses, Kaplan–Meier survival curves, and trajectory clustering (K-means).

Conclusions

This large real-world study confirms that mHLA-DR is a robust enrichment biomarker for identifying the most immunosuppressed septic shock patients at higher risk of adverse outcomes. Importantly, time-course analysis suggests that early immune downregulation may represent a physiological adaptation, while delayed and persistent immunosuppression is associated with worse outcomes. Early single time-point measurements may fail to identify patients who are unlikely to develop delayed immunosuppression. Tracking mHLA-DR trajectories after the initial ICU days is essential for detecting persistent immune dysfunction and selecting patients in case of immunostimulant approaches.