LAUSR

BACKGROUND Circulating complement C3 fragments released during septic shock might contribute to the development of complications such as profound hypotension and disseminated intravascular coagulation. The role of C3 in the course of septic shock varies in the literature, possibly because circulating C3 exists in different forms indistinguishable via traditional ELISA-based methods. We sought to test the relationship between C3 forms, measured by Western blotting with its associated protein size differentiation feature, and clinical outcomes. METHODS Secondary analysis of two prospective cohorts of patients with septic shock: a discovery cohort of 24 patents and a validation cohort of 181 patients. C3 levels were measured by Western blotting in both cohorts using blood obtained at enrollment. Differences between survivors and non-survivors were compared, and the independent prognostic value of C3 forms were assessed. RESULTS In both cohorts there were significantly lower levels of the C3-alpha chain in non-survivors than in survivors, and persisted after controlling for SOFA score. AUROC to predict survival was 0.65 (95% confidence interval [CI]: 0.56-0.75). At a best cutoff value (Youden) of 970.6 μg/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). CONCLUSION Circulating C3-alpha chain levels is a significant independent predictor of survival in septic shock patients.