Surviving septic patients endotyped with a functional assay demonstrate active immune responses

Area of Science:

• Immunology
• Critical Care Medicine
• Translational Research

Background:

• Sepsis involves a complex and heterogeneous immune response, traditionally assessed using static metrics.
• Novel approaches are needed to dynamically evaluate immune function in sepsis for improved patient stratification and treatment.

Purpose of the Study:

• To test if ex vivo functional tumor necrosis factor (TNF) expression and immune endotypes can model clinical outcomes in sepsis patients.
• To investigate the association between specific immune endotypes (based on IFNγ and TNF) and patient survival and discharge disposition.

Main Methods:

• Prospective observational study involving 107 sepsis patients, 68 non-septic ICU patients, and 46 healthy controls.
• Whole blood ELISpot assays measured ex vivo TNF and IFNγ expression on days 1, 4, and 7 of ICU admission.
• Patients were classified into four immune endotypes: 'immunocompetent', 'immunosuppressed', and two 'mixed' categories.

Main Results:

• Increased ex vivo TNF expression correlated with favorable discharge and lower in-hospital mortality in sepsis patients.
• The 'immunocompetent' endotype was associated with better discharge disposition and higher in-hospital survival compared to the 'immunosuppressed' endotype.
• Decreased total TNF and IFNγ expression were linked to increased 180-day mortality among septic patients.

Conclusions:

• Ex vivo assessment of functional TNF expression serves as a valuable predictor of clinical outcomes in sepsis.
• Early identification of an 'immunocompetent' immune endotype predicts improved survival and discharge success.
• Functional immune stratification of sepsis patients may guide the development of targeted immunomodulatory therapies.