Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model.
The nonclassical MHC class-I molecule, FcRn, salvages both IgG and albumin from degradation. Here we introduce a mechanism-based kinetic model for human to quantify FcRn-mediated recycling of both ligands based on saturable kinetics and data from the literature using easily measurable plasma concentrations rather than unmeasurable endosomal concentrations. The FcRn-mediated fractional recycling rates of IgG and albumin were 142% and 44% of their fractional catabolic rates, respectively. Clearly, FcRn-mediated recycling is a major contributor to the high endogenous concentrations of these two important plasma proteins. While familial hypercatabolic hypoproteinemia is caused by complete FcRn deficiency, the hypercatabolic IgG deficiency of myotonic dystrophy could be explained, based on the kinetic analyses, by a normal number of FcRn with lowered affinity for IgG but normal affinity for albumin. A simulation study demonstrates that the plasma concentrations of IgG and albumin could be dynamically controlled by both FcRn-related and -unrelated parameters.
Kim
Jonghan
J
Department of Internal Medicine, The Ohio State University, 425 Davis Heart and Lung Research Institute, Columbus, OH 43210, USA.
Hayton
William L
WL
Robinson
John M
JM
Anderson
Clark L
CL
D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D018448:Models, Immunological; D009223:Myotonic Dystrophy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D011504:Protein-Losing Enteropathies / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D011961:Receptors, Fc / Q000502:physiology*; D012709:Serum Albumin / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D012709:Serum Albumin; C100688:Fc receptor, neonatal