Complement component 4 (C4) (C4)

Complement component 4 (C4) is a critical protein in the innate immune system's complement cascade, functioning as a central node in both the classical and lectin activation pathways. Synthesized primarily in the liver, C4 is cleaved by the proteases C1s or MASP-2 into C4a (an anaphylatoxin) and C4b, which subsequently binds with C2 to form the C3-convertase enzyme complex (UniProt P0C0L4/P0C0L5; NIH StatPearls). Beyond its traditional role in opsonizing pathogens and facilitating inflammation, C4 plays a specialized role in the central nervous system by mediating C3-dependent synaptic pruning during brain development (Nature, 2016, 530:177-183). Genetic variations, particularly high copy numbers of the C4A isoform, have been strongly linked to an increased risk of schizophrenia, while C4 deficiency is a significant risk factor for the development of systemic lupus erythematosus (PubMed ID: 26814963). Current therapeutic strategies often target the activation of C4 rather than the protein itself, using C1s inhibitors like sutimlimab or C1 esterase inhibitors to manage complement-mediated hemolytic and inflammatory disorders (FDA Label: Enjaymo). Due to its role in pathogen clearance, pharmaceutical modulation of C4 requires careful monitoring for increased susceptibility to bacterial infections.

Other names

C4AC4BCPAMD2CPAMD3Acidic complement C4Basic complement C4

Inhibition of C1s-mediated cleavage of C4 into C4a and C4b, thereby preventing the formation of the C3-convertase (C4b2a) and halting the downstream complement cascade.