High C5a levels are associated with increased mortality in sepsis patients--no enhancing effect by actin-free Gc-globulin

Clin Biochem. 2008 Aug;41(12):974-80. doi: 10.1016/j.clinbiochem.2008.05.005. Epub 2008 May 27.

Abstract

Background: Immune paralysis of phagocytic cells due to excess of the complement activation product C5a has been proposed as a critical pathomechanism in sepsis. In vitro studies suggest an interaction of C5a with Group-specific globulin (Gc-globulin).

Study objectives: To examine the predictive value of serum concentrations of both, C5a and actin-free Gc-globulin, and their ratio for prognosis (mortality) of critically ill patients.

Patients: 154 critically ill (septic and non-septic) adult patients admitted to a Medical ICU and 38 healthy controls.

Measurements: Actin-free Gc-globulin and C5a were measured on ICU admission, alongside extensive laboratory, clinical and prospective outcome measures.

Results: Actin-free Gc-globulin and C5a serum concentrations were significantly reduced in critically ill patients compared with healthy controls. C5a levels, but not actin-free Gc-globulin, were significantly lower in patients with sepsis (n=112) than in critically ill patients without sepsis (n=42). C5a serum level was a prognostic parameter in patients with sepsis: High C5a levels were associated with increased mortality (at ICU and during follow-up). Although C5a and actin-free Gc-globulin were positively correlated, increasing serum concentrations of actin-free Gc-globulin did not enhance the C5a dependent effects in terms of prognosis or mortality in septic patients.

Conclusions: Investigation for C5a and/or actin-free Gc-globulin serum levels upon admission to the ICU may be helpful diagnostic tools. In patients with sepsis, C5a levels are an independent predictor of prognosis. However, different to pre-existing in vitro data, a clinically relevant interaction between actin-free Gc-globulin and C5a in terms of prognosis in severe inflammatory conditions is not given.

MeSH terms

  • Actins / blood
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers / blood
  • Complement C5a / chemistry*
  • Female
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Sepsis / diagnosis*
  • Sepsis / mortality*
  • Statistics, Nonparametric
  • Vitamin D-Binding Protein / blood*

Substances

  • Actins
  • Biomarkers
  • Vitamin D-Binding Protein
  • Complement C5a