Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study

Area of Science:

• Critical Care Medicine
• Immunology
• Translational Research

Background:

• Cellular immune dysfunction is prevalent in intensive care unit (ICU) patients, increasing complication risks.
• Clinically applicable methods are needed to detect immune dysfunction for targeted treatment.
• Identifying immune dysfunction markers can stratify secondary infection risk in critically ill patients.

Purpose of the Study:

• To confirm if cellular markers of immune dysfunction can stratify secondary infection risk in critically ill patients.
• To validate the use of neutrophil CD88, monocyte HLA-DR, and T regulatory cells as predictive markers.
• To assess the feasibility of standardized, multi-site flow cytometry for immune marker analysis.

Main Methods:

• A prospective observational cohort study involving 138 critically ill patients across four UK ICUs.
• Serial blood samples were analyzed using standardized flow cytometry for neutrophil CD88, monocyte HLA-DR, and T regulatory cell percentages.
• Patients were monitored for the development of secondary infections.

Main Results:

• Reduced neutrophil CD88, reduced monocyte HLA-DR, and elevated T regulatory cells were associated with increased secondary infection risk (ORs 2.18-3.44).
• The cumulative burden of immune dysfunction correlated with progressive infection risk, from 14% to 59%.
• Risk stratification was effective between days 3 and 9 post-ICU admission, not immediately upon admission.

Conclusions:

• Three cell surface markers (neutrophil CD88, monocyte HLA-DR, T regulatory cells) effectively predict secondary infection risk in critically ill patients.
• Standardized, multi-site flow cytometry is feasible for assessing these immune markers.
• This approach provides a tool for targeting immunomodulatory therapies in ICU patients.