Persistent Systemic Complement Activation Despite Increased Endogenous C1-Inhibitor Levels in Adult Burn Patients

ABSTRACT Background Burns induce prolonged inflammation that can compromise immune function and wound healing. The complement system is involved in immune responses, but its activation after burn remains incompletely characterized. This study aimed to characterize systemic complement activation over 30 days and explore associations with burn size and age. Methods Eighteen adult burn patients admitted to the Burn Center Beverwijk in 2016-2017 were included. Blood samples were collected at 2–6 days (n=11), 9–14 days (n=16), and 20–30 days (n=11) post-burn. Serum C3b/c, C4b/c, and C1-INH antigen and functional activity were measured by ELISA. CRP and leukocyte counts were obtained routinely. Eleven age- and sex-matched healthy donors served as controls. Patients were stratified by burn size (<10%, 10–20%, >20% TBSA). Associations with burn size and age were explored using linear mixed-effects models. Results CRP remained elevated throughout 30 days and was positively associated with burn size and age. Leukocytes peaked at 9–14 days and were not associated with burn size or age. C3b/c was significantly higher than controls at 2–6 days, 9–14 days, and 20–30 days post-burn. C4b/c was significantly higher than controls at 9–14 days only. No detectable associations between C3b/c or C4b/c and burn size or age were observed. C1-INH antigen levels were significantly higher than controls at 9–14 and 20–30 days. Functional C1-INH activity was significantly higher at 9–14 days only. Larger burn size was associated with higher C1-INH levels. Functional C1-INH levels were positively associated with age, whereas antigenic C1-INH levels were not. Conclusions Systemic complement activation persists for up to 30 days following burn injury, based on sustained C3b/c and transient C4b/c elevation, alongside increased C1-INH antigen and functional activity. Further studies should determine the clinical relevance of these findings and evaluate complement-targeted interventions.