Complement component 4 and C4b-binding protein (C4/C4BP)

Complement component 4 (C4) and C4b-binding protein (C4BP) constitute a critical regulatory axis within the classical and lectin pathways of the complement system. C4 is a central effector protein that, upon activation by proteases such as C1s or MASP-2, is cleaved into C4a (an anaphylatoxin) and C4b, which covalently attaches to surfaces to form the C3 convertase (C4b2a). C4BP serves as the primary fluid-phase regulator of this process, binding to C4b to accelerate the decay of the C3 convertase and acting as a cofactor for Factor I-mediated cleavage of C4b into inactive fragments like C4c and C4d. Dysregulation of this system is linked to various pathologies; for instance, C4 deficiency is a major genetic risk factor for systemic lupus erythematosus (SLE) due to impaired immune complex clearance, while excessive C4 activation contributes to tissue damage in inflammatory conditions and transplant rejection. Therapeutic strategies include the use of C1s or MASP-2 inhibitors to prevent C4 activation, as well as the development of recombinant C4BP or C4BP-fusion proteins to treat infections and autoimmune diseases by modulating complement activity and inflammatory signaling.

Other names

C4C4BPComplement C4C4b-binding proteinComplement component 4AComplement component 4BC4AC4BC4BPAC4BPB

Inhibition of C1s or MASP-2 mediated cleavage of C4; inhibition of C4 covalent binding to surfaces; enhancement of C4b degradation via cofactor activity for Factor I; acceleration of C3 convertase decay.