Complement component 3 and Complement component 4 (C3/C4)

Complement component 3 (C3) and Complement component 4 (C4) are central glycoproteins of the innate immune system's complement cascade [1, 3]. C3 serves as the essential hub where the classical, lectin, and alternative pathways converge, while C4 is a critical component of the classical and lectin pathway C3 convertase [6, 14]. Upon activation, these proteins are proteolytically cleaved into bioactive fragments: anaphylatoxins (C3a, C4a) that mediate inflammation and opsonins (C3b, C4b) that facilitate phagocytosis and the formation of the membrane attack complex [4, 10]. Dysregulation or excessive consumption of C3 and C4 is a hallmark of various autoimmune and inflammatory diseases, most notably systemic lupus erythematosus (SLE) and C3 glomerulopathy [2, 8]. Therapeutic intervention at the level of C3, such as with the pegylated peptide pegcetacoplan, has been approved for treating paroxysmal nocturnal hemoglobinuria (PNH) and geographic atrophy [7, 13]. Monitoring serum levels of C3 and C4 is a standard clinical biomarker for assessing disease activity and treatment efficacy in conditions involving complement consumption [16, 19]. Genetic variations, such as C4 copy number variations, have also been linked to susceptibility to autoimmune disorders and neurodevelopmental conditions like schizophrenia [17]. Overall, C3 and C4 represent critical nodes for both diagnostic monitoring and therapeutic targeting within the complement system [5, 11].

Other names

C3C4Complement C3Complement C4CPAMD1CPAMD2CPAMD3

Inhibition of C3 cleavage and convertase assembly, preventing the generation of downstream effector molecules and the amplification of the complement cascade [7, 12]. Upstream inhibition of C1s or MASP-2 also prevents the cleavage of C4 [5].