Fc-gamma receptors and complement system proteins (FcγR and Complement)

Fc-gamma receptors (FcγRs) and complement system proteins are the primary molecular targets through which Intravenous Immunoglobulin (IVIG) exerts its immunomodulatory and anti-inflammatory effects [1, 2]. FcγRs are a family of cell surface glycoproteins, including activating (FcγRI, FcγRIIa/c, FcγRIIIa) and inhibitory (FcγRIIb) types, expressed on various immune cells where they mediate effector functions such as phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) [2, 7, 12]. The complement system consists of plasma proteins like C1q, C3, and C4 that trigger a proteolytic cascade leading to opsonization and inflammation [5]. In autoimmune and inflammatory diseases, IVIG acts by saturating activating FcγRs to block the binding of pathogenic autoantibodies, potentially upregulating the inhibitory receptor FcγRIIb, and neutralizing activated complement components to mitigate tissue injury [1, 3, 4, 5]. Additionally, IVIG competes for binding to the neonatal Fc receptor (FcRn), thereby accelerating the degradation of harmful endogenous antibodies [6, 12]. These multifaceted interactions make the FcγR and complement pathways central to the therapeutic management of conditions such as immune thrombocytopenia (ITP), Kawasaki disease, and various inflammatory neuropathies [2, 10].

Other names

Fc gamma receptorsComplement systemFcγRCD64CD32CD16C1qC3C4Receptors for the Fc region of IgG

Competitive inhibition of activating Fc-gamma receptors (FcγRs) by high-dose IgG; upregulation of the inhibitory receptor FcγRIIb; saturation of the neonatal Fc receptor (FcRn) to increase clearance of pathogenic autoantibodies; and scavenging of activated complement fragments (C3b, C4b) to prevent complement-mediated tissue damage.