(1577) Complement Profiles in Septic Pediatric Patients With Multiple Organ Dysfunction Syndrome

Introduction: Multiple organ dysfunction syndrome (MODS) due to sepsis is a common cause of mortality in pediatric intensive care units (PICU). In a study of transplant-associated thrombotic microangiopathy, children with MODS receiving complement-mediated therapy had ~50% reduction in 1-year mortality. Despite its well-established role in sepsis, the complement cascade remains poorly investigated in critically ill pediatric patients.

Methods: We performed a multi-part prospective cohort study on septic children admitted to a single center PICU. Patients were placed into MODS and single organ dysfunction (SOD) cohorts. Elective surgery patients comprised the control cohort. Samples were collected within 48 hours of enrollment and measured for concentration of soluble C5b9 (sC5b9), a clinically available biomarker of complement activation, using an enzyme-linked immunosorbent assay. Descriptive analysis of risk factors and clinical outcomes was performed for septic patients based on sC5b9 concentrations. Finally, additional complement proteins were measured with a multiplex immunofluorescence assay and evaluated with multiple linear regression analysis.

Results: Fifteen patients were enrolled in the study - MODS (n=4), SOD cohort (n=4), control cohort (n=7) - with sC5b9 concentration (median,(min-max) ng/mL) of 1,227 (135-14,916), 176 (40-412), and 45 (11-83), respectively. The majority of patients in the high and medium sC5b9 cohorts had a bacterial etiology and incidence of renal dysfunction. Analysis of multiplex assay results revealed that sC5b9 was positively associated with C3 (p = 0.002) and negatively associated with C5 (p = 0.028). No other complement proteins achieved significance.

Conclusions: This is the first prospective study to measure sC5b9 in critically ill children with organ dysfunction from sepsis. Concentrations were notably highest in septic patients with MODS although significance could not be established given the small study sample size. A bacterial etiology of sepsis and incidence of renal dysfunction appear more closely related to sC5b9 concentrations than the number of dysfunctional organs. The convergent pathway is upregulated along with the classical and lectin pathways, while the alternative pathway changes appears variable.