We read the recent paper by Unnewher and colleagues (1) with interest. This paper adds to the growing literature on the role of C5a in human critical illness. The finding of reduced neutrophil CD88 expression in human sepsis was first identified by Furebring and colleagues in 2002 (2). This finding was confirmed in a study of patients with hospital-acquired sepsis (3), in which we demonstrated a correlation between CD88 expression and neutrophil phagocytic function. This was further developed in a longitudinal cohort study demonstrating reduced neutrophil CD88 predicted subsequent diagnosis of nosocomial infection (4). Interestingly, we found that low CD88 was not specific to patients presenting to the intensive care unit (ICU) with sepsis, and patients with sterile insults showed similar reductions in expression. This tallied with previous findings from Huber-Lang’s team demonstrating reduced neutrophil CD88 expression in humans following major trauma (5). This apparently maladaptive response to infective and sterile insults may help explain why secondary infections remain so prevalent in the ICU.
The association between low neutrophil CD88 and mortality from septic shock is supported by our recent analysis of a range of markers of immune cell dysfunction in critical illness (6). Low neutrophil CD88 was the strongest predictor of subsequent nosocomial infection and a significant predictor of death from infective insults but, interestingly, not of death from sterile insults.
The crucial next step in the field of complement-mediated immune dysfunction will be effective therapies, either targeting the complement pathway itself or down-stream mediators of dysfunction (4).
- Copyright © 2013 by The American Association of Immunologists, Inc.
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