Complement system components and Fc-binding plasma proteins

The complement system and Fc-binding plasma proteins constitute a complex network of proteins essential for the innate immune response and the regulation of antibody-mediated immunity (Janeway's Immunobiology, 2001). The complement system consists of over 30 proteins that circulate in an inactive form and are activated through classical, lectin, or alternative pathways, leading to the formation of the membrane attack complex (MAC) and the release of pro-inflammatory anaphylatoxins like C3a and C5a (Ricklin et al., Nature Immunology, 2010). Fc-binding plasma proteins, most notably the neonatal Fc receptor (FcRn), play a pivotal role in maintaining the long half-life of immunoglobulin G (IgG) and albumin by protecting them from lysosomal degradation (Roopenian & Akilesh, Nature Reviews Immunology, 2007). Dysregulation or overactivation of these pathways is a primary driver in diseases such as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and generalized myasthenia gravis (gMG) (Morgan & Harris, Nature Reviews Drug Discovery, 2015). Therapeutic intervention in this space has expanded significantly, with drugs like eculizumab and ravulizumab targeting C5 to prevent terminal complement activation, and newer agents like efgartigimod targeting FcRn to reduce pathogenic IgG levels (Howard et al., The Lancet Neurology, 2021). This target entry is considered incorrect as a single entity because it represents a broad functional category of diverse proteins rather than a specific molecular target.

Other names

Complement systemFc-binding proteinsHumoral immune factorsComplement cascade proteins

Drugs targeting this group typically act by inhibiting specific proteases in the complement cascade (e.g., C1s, C3, or C5) to prevent the formation of pro-inflammatory mediators and the membrane attack complex, or by blocking Fc-receptors (e.g., FcRn) to accelerate the degradation of pathogenic IgG antibodies (Ricklin et al., Nature Immunology, 2010; Roopenian & Akilesh, Nature Reviews Immunology, 2007).