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).


OBJECTIVE
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.


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


METHODS
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.
Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Aachen University (RWTH), Aachen, Germany. ogressner@ukaachen.de
Olav A
OA
Gressner
Alexander
A
Koch
Edouard
E
Sanson
Christian
C
Trautwein
Frank
F
Tacke
D000199:Actins / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015936:Complement C5a / Q000737:chemistry*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D018805:Sepsis / Q000175:diagnosis* / Q000401:mortality*; D018709:Statistics, Nonparametric; D014809:Vitamin D-Binding Protein / Q000097:blood*
D000199:Actins; D015415:Biomarkers; D014809:Vitamin D-Binding Protein; D015936:Complement C5a