Circulating Complement C3-Alpha Chain Levels Predict Survival of Septic Shock Patients

Abstract

Abstract Septic shock is a critical clinical condition with a high mortality rate. Previous observations have suggested that circulating complement C3 fragments, released during septic shock, might contribute to the development of complications such as profound hypotension and disseminated intravascular coagulation, resulting in a more severe disease course and a poorer outcome. However, there are conflicting reports regarding the role of C3 in the course of septic shock. Because circulating C3 exists in different sizes through enzymatic processing or spontaneous hydrolysis, these previous studies, which used ELISA-based methods, would not have distinguished among different C3 species. We have used Western blotting, with its associated protein size differentiation feature, to investigate the forms of circulating C3 in two cohorts of septic shock patients: a discovery cohort of 24 patents and a validation cohort of 181 patients. In both cohorts there were significantly lower levels of the C3-alpha chain in non-survivors than in survivors. In addition, the levels of the C3-alpha chain significantly correlated with days of survival. ROC and AUC analyses showed an AUC=0.65 (95% confidence interval [CI]: 0.56–0.75). At a best cutoff value (Youden) of 970.6 mg/ml, the test demonstrated a sensitivity of 68.5% and specificity of 61.5%. At this cutoff point, Kaplan-Meier survival analysis showed that patients with lower levels of C3-alpha chain had significantly lower survival than those with higher levels (p < 0.001). Thus, circulating C3-alpha chain levels in septic shock patients may predict survival rates.