The complement system is the backbone of the innate immune system and was discovered over 100 years ago based on the assumption that it complemented the immune cells known at the time. Since then, more than 50 components of this system have been described. Depending on the trigger, there are three different activation pathways of the complement system: the classical, the alternative, and the lectin pathways.
At the end of these three pathways, the membrane attack complex (C5b-9) is formed, which can directly kill pathogens and cells. Highly effective substances are produced as “byproducts.” Some mark (opsonize) particles so that they can be phagocytosed by phagocytes, while others are proinflammatory and attract immune cells.
In rare cases, there is defective or reduced production of complement system factors, which can lead to complement deficiency and, consequently, to increased susceptibility to infection or heightened autoimmunity. If the cause of the complement deficiency is congenital, affected patients often develop severe infectious diseases—such as meningococcal meningitis or severe pneumonia—as early as childhood. In some diseases, such as systemic lupus erythematosus or hereditary angioedema, complement factors are depleted faster than they are produced, and can thus serve as an indicator or measure of disease activity.
Complement assays are therefore indicated in the following cases: when investigating immunodeficiencies—for example, in cases of recurrent infections with encapsulated pathogens—and to detect increased activation or inadequate regulation in the context of autoimmune diseases and nephritis. Another indication is the measurement of C1 esterase inhibitor in angioedema.