Molecular diagnostics in sepsis: from bedside to bench.

Area of Science:

• Genomics
• Molecular Biology
• Medical Diagnostics

Background:

• Recent in vitro data suggests microarray expression profiles may diagnose sepsis.
• The study aimed to differentiate in vivo between sterile and infectious causes of systemic inflammation.

Purpose of the Study:

• To test the hypothesis that microarray expression profiles can diagnose sepsis.
• To distinguish between sterile and infectious causes of systemic inflammation.

Main Methods:

• Exploratory studies used spleen samples from septic patients and mice with abdominal sepsis.
• A sepsis classification model was developed and tested on mouse blood samples.
• Gene expression data from human and mouse samples were analyzed using cross-validation.

Main Results:

• Classification accuracy for sepsis prediction was 67.1% in human spleen, 96% in mouse spleen, and 94.4% in mouse blood.
• Nine common mouse inflammatory response genes were identified, with six mapped to a single pathway.
• Nested cross-validation was used to estimate classification accuracy.

Conclusions:

• Sepsis induces distinct changes in mouse leukocyte gene expression.
• These gene expression changes can be utilized to diagnose sepsis and differentiate it from general systemic inflammation.