Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration*

Area of Science:

• Immunology
• Hematology
• Critical Care Medicine

Background:

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Early prediction of sepsis evolution is crucial for timely intervention and improved patient outcomes.
• Leukocyte subsets play a significant role in the host's immune response to sepsis.

Purpose of the Study:

• To identify leukocyte subsets capable of predicting early sepsis evolution (deterioration or stability/improvement) at 48 hours.
• To assess the prognostic value of leukocyte subsets on sepsis-related mortality.
• To investigate the immunosuppressive properties of immature granulocytes in sepsis.

Main Methods:

• Analysis of 23 peripheral blood leukocyte subsets using 10-color flow cytometry.
• Exploration of T-cell killing activity of immature granulocytes via a specialized sorting method.
• Inclusion of 177 adult patients admitted to ICUs and emergency departments with sepsis onset < 24 hours.

Main Results:

• Decreased CD10 and CD16 expression on granulocytes were key indicators of sepsis.
• Immature granulocytes (defined by CD10 and CD16 thresholds) predicted sepsis deterioration with 57-70% sensitivity and 78-82% specificity.
• Survival rates at day 30 were significantly lower in patients with increased CD10 and/or CD16 granulocytes (p < 0.001).
• A subset of CD16 immature granulocytes identified as CD14/CD24 myeloid-derived suppressor cells exhibited T-cell killing capability.
• Elevated CD16 immature granulocytes correlated with CD3 and CD4 T-cell lymphopenia in deteriorating patients.

Conclusions:

• Circulating immature granulocytes are predictive of early sepsis deterioration.
• Immature granulocytes are enriched in myeloid-derived suppressor cells.
• These myeloid-derived suppressor cells may induce T-cell lymphopenia, contributing to sepsis-induced immunosuppression.