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Abstract
Immunoglobulin G (IgG), the major antibody in the serum, is involved with clearing foreign pathogens, such as bacteria and viruses. Conversely, self-reactive antibodies can be responsible for the pathogenesis of autoimmune diseases such as rheumatoid arthritis. The relatively long serum half-lives of IgG have been attributed to a recycling mechanism largely controlled by the neonatal Fc receptor (FcRn). Engineered antibodies with increased affinities for FcRn (Abdegs) can indirectly influence the clearance rates of endogenous IgG by inhibiting FcRn function. As such, Abdegs have potential functions for the treatment of autoimmune diseases. In this work, we develop a pharmacokinetic model that describes the FcRn-mediated mice endogenous IgG recycling pathway. We further improve the model by introducing hypothetical exponential functions for describing endogenous IgG-FcRn recycle and degradation pathways to predict half-lives of injected Abdeg Mutants with altered binding affinities. These simulation results are in agreement with the experimentally observed results.
