The neonatal Fc receptor: Key to homeostasic control of IgG and IgG-related biopharmaceuticals

IgG and albumin are the most abundant proteins in the circulation and have the longest half-lives. These properties are due to a unique receptor, the neonatal Fc receptor (FcRn). Although FcRn is named for its function of transferring IgG across the placenta from maternal to fetal circulation, FcRn functions throughout life to maintain IgG and albumin concentrations. FcRn protects IgG and albumin from intracellular degradation and recycles them back into the circulation. Clinical trials have confirmed that pathogenic antibodies can be depleted by blocking this homeostatic function of FcRn. Moreover, understanding the molecular interactions between IgG and FcRn has resulted in the design of therapeutic monoclonal antibodies with more efficacious pharmacokinetics. As a result of genetic engineering these monoclonals can be delivered at lower doses and at longer intervals. More recent findings have demonstrated that FcRn enhances phagocytosis by neutrophils, immune complex clearance by podocytes and antigen presentation by dendritic cells, macrophages, and B cells. This minireview highlights the relevance of FcRn to transplantation.