The complement system

The complement system is the human’s first line of defense against microbial pathogens, and it holds important housekeeping and infection/inflammation control roles. It is composed of a series of soluble and cell-bound proteins that are activated in a cascade effect, similar to the coagulation pathways. There are different pattern-recognizing molecules that activate the complement system in response to different stimuli or threats, and three known complement activation pathways: classical, lectin, and alternative. All pathways converge at the C3 component. The main outputs of the complement system action are cell lysis, pro-inflammatory anaphylatoxins, and opsonization of targets. Laboratory testing is relevant in the setting of suspected complement deficiencies, autoimmune diseases, and a series of complement-mediated injuries. Most common assays measure complement lytic activity and the different complement component concentrations. Specialized testing includes evaluation of autoantibodies against complement components, activation fragments, and genetic studies.