TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

Area of Science:

• Immunology
• Genetics
• Critical Care Medicine

Background:

• Tumour necrosis factor (TNF) is a key pro-inflammatory cytokine implicated in sepsis.
• Previous studies on TNF gene polymorphisms and sepsis have yielded inconsistent findings.
• Understanding the genetic and protein level associations with sepsis is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate if common polymorphisms in TNF, TNFRSF1A, and TNFRSF1B genes affect protein levels.
• To determine if these polymorphisms or haplotypes are associated with sepsis susceptibility, severity, or outcome.
• To explore the relationship between circulating TNF and its soluble receptor levels and clinical parameters in sepsis.

Main Methods:

• Genotyping of common polymorphisms in TNF, TNFRSF1A, and TNFRSF1B genes.
• Measurement of plasma levels of TNF, soluble TNFRSF1A (sTNFRSF1A), and soluble TNFRSF1B (sTNFRSF1B).
• Correlation analysis between genetic variations, protein levels, and clinical data including Sequential Organ Failure Assessment (SOFA) scores in 213 Caucasian sepsis patients.

Main Results:

• Plasma levels of TNF, sTNFRSF1A, and sTNFRSF1B were significantly higher in non-survivors compared to survivors.
• Increasing levels of sTNFRSF1A and sTNFRSF1B positively correlated with organ dysfunction, particularly renal dysfunction (SOFA score).
• No significant associations were found between TNF or TNF receptor gene polymorphisms/haplotypes and sepsis susceptibility, severity, or patient outcome.

Conclusions:

• While elevated TNF and soluble receptor levels are linked to sepsis mortality and severity, common polymorphisms in these genes do not appear to influence these outcomes.
• The role of TNF gene polymorphisms in sepsis susceptibility and outcome remains uncertain.
• Soluble TNF receptors may serve as important biomarkers for sepsis severity and organ dysfunction.