Measures of Classical and Alternative Complement Function in Serum as Markers in Critical Care

Abstract

The human complement system is a crucial component of the host response to pathogen invaders, cellular stress, and injury – all of which are common causes and manifestations of critical illness. The complement cascade can be activated by alternative, classical, and lectin pathways that function as immune recognition pathways. Yet, the capacity of the complement system to respond to infection and injury depends not only on the ability to activate but also on effective regulation to prevent complement factor exhaustion, limit inflammation, and preserve complement function to respond to threats. Therefore, measurements of complement pathway function and levels of specific complement proteins may serve as useful biomarkers during critical illness. Complement activity or function is widely variable during critical illness caused by sepsis and other infections, acute respiratory failure including pneumonia, and during the massive injury of trauma. Preserved complement function has been associated with improved outcomes across numerous investigations. However, whether preservation of complement function is a causal mechanism or the consequence of decreased burden of pathogen or injury is unclear and worthy of future research. Herein, we present key biology of the complement system, review assays of complement function, and describe key findings of the existing literature evaluating complement function during critical illness. We further present potential topics for future research on the complement system during critical illness.