Complement Overreaction

The complement system, in its enzyme cascade construction resembling the coagulation system, is built from about 25 different serum proteins and about 10 different cell membrane proteins and is at work every day, in the healthy individual. 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 different diseases - worst is C3 deficiency which, if untreated, is lethal at young age. Genetic polymorphisms of C3 or of regulatory proteins can be predisposing for definite diseases, such as hemolytic uremic syndrome, HUS. If complement activation is something good for the body, its overreaction or its endless activation by the autoantigen-antibody complexes leads to severe, sometimes acute 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).

The extent of complement overreaction can be measured by exploring the concentration of complement breakdown products, such as C3a and C5a or C3d. The 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 positioned for clinical development as we will survey in february 2011 at the zurich-complement-symposium (URL in construction)

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