Neonatal Fc receptor

As glomerular filtration has an approximate molecular size limit of 20-30 kDa, mAbs do not undergo filtration in the kidneys due to their relatively large size. The situation is different, however, for low molecular-mass antibody fragments, which can be filtered. Tubular secretion has not been reported to occur to any significant extent for mAbs, and peptides/small proteins are readily reabsorbed in the proximal or distal tubule of the nephron (potentially also mediated by the neonatal Fc receptor, Fc-Rn), or are even metabolized. Thus, renal elimination in total is uncommon or low for mAbs. Biliary excretion of mAbs has been reported only for IgA molecules, and only to a very small extent. Therefore, total clearance (CL) does usually not comprise renal or biliary clearance. 

Similar to that of endogenous IgG, the plasma half-life for human IgGl, IgG2, and IgG4 therapeutic antibodies can be up to three to four weeks in humans. This long plasma half-life has been ascribed to the protection from catabolism conferred by the neonatal Fc receptor (FcRn) as part of its role in regulating IgG homeostasis [3-5] (see below). In beta-2-microglobulin-... 

Zhu X, Meng G, Dickinson BL, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol 2001 166(5) 3266-76. 

Schlachetzki F, Zhu C, Pardridge WM. Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J Neurochem 2002 81(l) 203-6. 

Mikulska JE, Pablo L, Canel J, Simister NE. Cloning and analysis of the gene encoding the human neonatal Fc receptor. Eur J Immunogenet 2000 27(4) 231-40. 

Zhu X, Peng J, Raychowdhury R, Nakajima A, Lencer WI, Blumberg RS. The heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic reticulum by forming oligomers in the absence of beta2-microglobulin association. Biochem J 2002 367(Pt 3) 703-14. 

Datta-Mannan A, Witcher DR, Tnag Y, Watkins J, Wroblewski VJ. Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor. / Biol Chem 2007 282(3) 1709-17. http //www.ibc.org/cgi/doi/10.10741/ jbc.M607161200... 

McCarthy KM, Yoong Y, Simister NE. Bidirectional transcytosis of IgG by the rat neonatal Fc receptor expressed in a rat kidney cell line A system to study protein transport across epithelia. J Cell Sci 2000 113 1277-85. 

C). The neonatal Fc receptor, which is related structurally to Class IMHC antigens (Section D,5), is one of three major types of Fc receptor. The other two are the receptors for Fey (of IgG) and Fee (of IgE). 

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