Complement system components (C3 and C4) (Complement)

The complement system consists of a series of plasma proteins that play a critical role in the innate immune response and inflammation. In many autoimmune and inflammatory diseases, overactivation of the complement cascade leads to tissue damage through opsonization and the formation of the membrane attack complex. Intravenous immunoglobulin (IVIG) acts as a therapeutic modulator by interacting directly with various complement components. Specifically, IVIG can scavenge active fragments such as C3b and C4b via its Fab and Fc regions, effectively neutralizing their pro-inflammatory effects (Basta et al., 2003). This interaction prevents the amplification of the complement cascade and protects host cells from complement-mediated destruction (Lutz et al., 2004). Consequently, IVIG is a vital treatment for conditions like Myasthenia Gravis and Guillain-Barré syndrome where complement-mediated injury is a primary driver of pathology (StatPearls, 2023). Monitoring serum C3 and C4 levels can help assess the efficacy of IVIG in modulating the complement system during treatment.

Other names

C3C4C1qComplement cascadeComplement proteins

IVIG interacts with complement components through both its Fab and Fc regions. The Fab fragments can specifically bind to and neutralize active complement fragments like C3b and C4b, preventing their deposition on host tissues and the subsequent formation of the membrane attack complex. Additionally, the Fc portion of IVIG can bind to C1q, diverting it from its normal targets and thereby inhibiting the initiation of the classical complement pathway.