Complement component 4 (C4)

Complement component 4 (C4) is a large, disulfide-bonded glycoprotein (~200 kDa), comprising three peptide chains (α, β, γ) and encoded by the genes C4A and C4B, located in the human leukocyte antigen (HLA) region on chromosome 6[1][7][2]. C4 is a key protein in the classical and lectin pathways of the complement system, acting as an essential mediator that links pathogen recognition (by antibodies or carbohydrate structures) to effector mechanisms of the immune response[1][3][4][7]. Upon activation by proteases C1s (classical pathway) or MASP-2 (lectin pathway), C4 is cleaved into C4a (smaller fragment, released into plasma) and C4b (large fragment, covalently binds to target surfaces and serves as an opsonin)[1][7][4][10]. C4b participates in the assembly of C3 convertase, critical for complement cascade amplification and downstream immune defense activities[1][10]. Deficiency or dysfunction of C4 leads to increased susceptibility to bacterial and viral infections as well as autoimmune conditions, particularly systemic lupus erythematosus and related disorders[6][7]. Clinical measurement of C4 in blood is routinely used as a biomarker for diagnosing, monitoring, and prognosing autoimmune diseases and immune deficiencies; the cleavage product C4d is another recognized marker for complement pathway activation and tissue injury[1][6][7]. While there are no widely approved drugs that directly target C4, the complement pathway is an active area of drug development, with several agents targeting upstream or downstream complement factors to control unwanted inflammation or autoimmunity. Safety challenges include increased infection risk and possible disease exacerbation if the pathway is over- or under-modulated[6][7][1].

Other names

Complement C4C4AC4B

Inhibition or modulation of complement activation (targeted by experimental or emerging drugs to dampen complement activity in autoimmune or inflammatory conditions)