American Society of Hematology

Fig. 1.

$Fig. 1. Models of the role of FcRn in the degradation of IgG and of the 2-compartment pharmacokinetics used for the simulations. / (A) IgG is taken up by aspecific pinocytosis into endosomes. At decreasing pH (approximately pH 6), IgG binds to FcRn in the wall of the endosomes, after which the IgG-FcRn complexes are recycled to the cell surface, where IgG is released because of higher pH. IgG not bound to FcRn is delivered to lysosomes and degraded. At higher IgG concentrations FcRn will become saturated, resulting in a smaller proportion of the endocytosed IgG rescued by FcRn from degradation in the lysosomes. This results in a shorter plasma half-life (or higher fractional clearance rate) with a minimum value determined by the pinocytosis rate when all FcRn is saturated. (B) Elimination from the plasma compartment, consisting of cellular uptake with saturable return as depicted above, is a nonlinear process described by a concentration-dependent FCR.$

Models of the role of FcRn in the degradation of IgG and of the 2-compartment pharmacokinetics used for the simulations.

(A) IgG is taken up by aspecific pinocytosis into endosomes. At decreasing pH (approximately pH 6), IgG binds to FcRn in the wall of the endosomes, after which the IgG-FcRn complexes are recycled to the cell surface, where IgG is released because of higher pH. IgG not bound to FcRn is delivered to lysosomes and degraded. At higher IgG concentrations FcRn will become saturated, resulting in a smaller proportion of the endocytosed IgG rescued by FcRn from degradation in the lysosomes. This results in a shorter plasma half-life (or higher fractional clearance rate) with a minimum value determined by the pinocytosis rate when all FcRn is saturated. (B) Elimination from the plasma compartment, consisting of cellular uptake with saturable return as depicted above, is a nonlinear process described by a concentration-dependent FCR.

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