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

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.