Parameter Identification for a Model of Neonatal Fc Receptor-Mediated Recycling of Endogenous Immunoglobulin G in Humans.

Salvage of endogenous immunoglobulin G (IgG) by the neonatal Fc receptor (FcRn) is implicated in many clinical areas, including therapeutic monoclonal antibody kinetics, patient monitoring in IgG multiple myeloma, and antibody-mediated transplant rejection. There is a clear clinical need for a fully parameterized model of FcRn-mediated recycling of endogenous IgG to allow for predictive modeling, with the potential for optimizing therapeutic regimens for better patient outcomes. In this paper we study a mechanism-based model incorporating nonlinear FcRn-IgG binding kinetics.

Analysis of a Compartmental Model of Endogenous Immunoglobulin G Metabolism with Application to Multiple Myeloma.

Immunoglobulin G (IgG) metabolism has received much attention in the literature for two reasons: (i) IgG homeostasis is regulated by the neonatal Fc receptor (FcRn), by a pH-dependent and saturable recycling process, which presents an interesting biological system; (ii) the IgG-FcRn interaction may be exploitable as a means for extending the plasma half-life of therapeutic monoclonal antibodies, which are primarily IgG-based. A less-studied problem is the importance of endogenous IgG metabolism in IgG multiple myeloma. In multiple myeloma, quantification of serum monoclonal immunoglobulin plays an important role in diagnosis, monitoring and response assessment.