Complement System

The complement system, in its enzyme cascade construction resembling the coagulation system, is built from 48 proteins, 9 different cell membrane proteins and is at work every day, in the healthy individual. The 4th International Congress on Controversies in Rheumatology and Autoimmunity (CORA) will be held in Bologna, Italy march 2017 ; more information displayed on the Workshop Website and will feature a special session on complement.

Complement helps us for defense against infectious agents and the central component, C3 (1.3 grams/liter) is synthesized by the liver to be turned over by 50% daily. Genetic deficiencies of complement components cause disease – worst is C3 deficiency which, if untreated, is lethal at young age; may be CRISP Cas9 technology will help.

Genetic polymorphisms of C3 or of regulatory proteins can be predisposing for definite diseases, such as haemolytic uremic syndrome, HUS. If complement activation maintains health, its overreaction/persistent activation by autoantigen-antibody complexes leads to inflammatory reaction in those organs that contain much of the reticuloendothelial system (lung, liver, spleen, bone marrow) or where the microvasculature is strongly developed (kidney, skin). C5a may prime retinal pigment epithelial cells for inflammasome activation. Crosstalk C –>  growth factor receptors, inflammasomes, metabolic sensors and the Notch system is seen.

The extent of complement overreaction can be measured by exploring the concentration of complement breakdown products, such as C3a and C5a or C3d. Therapeutic downregulation of complement is possible and finds increasing interest of clinicians: TP10, soluble complement receptor 1 is a novel inhibitor for C3 and C5 convertases and eculizumab is a humanized, monoclonal, single-chain antibody fragment that inhibits C5 – both are promising therapeutic options.

Diagnostic procedures are commercially available (e.g. from eurodiagnostica.com).
Trials