Polyclonal human immunoglobulin G (IgG)

Polyclonal human immunoglobulin G (IgG) is the most abundant antibody isotype in the human circulatory system, serving as a cornerstone of the adaptive immune response by identifying and neutralizing foreign pathogens such as bacteria and viruses [StatPearls, 2023]. Structurally, IgG is a glycoprotein composed of two heavy and two light chains, featuring a variable region for antigen binding and a constant (Fc) region that interacts with immune effector cells and the neonatal Fc receptor (FcRn) [UniProt, 2024]. While vital for health, IgG becomes a therapeutic target in autoimmune conditions where 'autoantibodies' mistakenly target the body's own tissues, leading to diseases such as myasthenia gravis or immune thrombocytopenia [Nature Reviews Drug Discovery, 2017]. Therapeutic interventions targeting IgG aim to reduce its concentration or neutralize its activity; for instance, FcRn inhibitors block the recycling pathway that normally extends the half-life of IgG, leading to a rapid reduction in circulating antibody levels [FDA, 2021]. Furthermore, enzymatic depletion using agents like imlifidase can provide immediate reduction of IgG for high-risk procedures like sensitized organ transplantation [NEJM, 2019].

Other names

Human IgGImmunoglobulin GGamma globulinPolyclonal IgGSerum IgG

Drugs targeting polyclonal human IgG primarily act through two distinct mechanisms: 1) Competitive inhibition of the neonatal Fc receptor (FcRn), which prevents the salvage and recycling of IgG molecules from endosomes, thereby accelerating their lysosomal degradation and lowering total serum IgG levels [Nature Reviews Drug Discovery, 2017; FDA, 2021]. 2) Direct proteolytic cleavage by IgG-specific endopeptidases, such as imlifidase, which breaks the IgG heavy chains at a specific site, rendering the antibodies unable to bind Fc receptors or activate complement [NEJM, 2019].