Complementremmers

Complementremmers, or complement inhibitors, are substances that block the activation or effector functions of the complement system, a proteolytic cascade in the innate immune system that enhances antibody responses and helps clear pathogens. The system can be activated via classical, lectin, or alternative pathways, all converging on C3 and leading to inflammation, opsonization, and formation of the membrane attack complex (MAC). In normal physiology, this activity is tightly regulated by endogenous inhibitors to prevent damage to host tissues.

Endogenous regulators include C1 esterase inhibitor, factor H, factor I, and membrane-associated proteins such as CD55 and CD59. Defects or dysregulation of these controls can contribute to disease, prompting the development of therapeutic complement inhibitors. Pharmacological agents aim to prevent excessive or misdirected activation in conditions such as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy, or certain forms of age-related macular degeneration, among others. Therapeutic strategies target different steps: blocking initiation (C1 inhibitors), preventing formation or activity of C3/C5 convertases, inhibiting C5 to prevent MAC formation, or antagonizing C5a receptors to reduce inflammation. Small-molecule inhibitors and monoclonal antibodies are common formats.

Examples of therapeutic inhibitors include C5 inhibitors (eculizumab, ravulizumab), C3 inhibitors (pegcetacoplan), C1 esterase inhibitors (berinert, Cinryze), and agents targeting the alternative pathway such as factor B or factor D inhibitors, as well as C5a receptor antagonists. Treatment often requires vaccination against encapsulated bacteria due to infection risk.

See also: complement system, PNH, aHUS.