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Neonatal Fc receptor

August 28, 2023

The neonatal Fc receptor (also FcRn, IgG receptor FcRn large subunit p51, or Brambell receptor) is a protein that in humans is encoded by the FCGRT gene.[1][2][3] It is an IgG Fc receptor which is similar in structure to the MHC class I molecule and also associates with beta-2-microglobulin.[4][5] In rodents, FcRn was originally identified as the receptor that transports maternal immunoglobulin G (IgG) from mother to neonatal offspring via mother's milk, leading to its name as the neonatal Fc receptor.[6][7] In humans, FcRn is present in the placenta where it transports mother's IgG to the growing fetus.[1][8] FcRn has also been shown to play a role in regulating IgG and serum albumin turnover.[9][10][11][12][13] Neonatal Fc receptor expression is up-regulated by the proinflammatory cytokine, TNF, and down-regulated by IFN-γ.[14]

Fc fragment of IgG, receptor, transporter, alpha
Identifiers
SymbolFCGRT
NCBI gene2217
HGNC3621
OMIM601437
RefSeqNM_004107
UniProtP55899
Other data
LocusChr. 19 q13.3
Search for
StructuresSwiss-model
DomainsInterPro

Interactions of FcRn with IgG and serum albumin Edit

In addition to binding to IgG, FCGRT has been shown to interact with human serum albumin.[10][15] FcRn-mediated transcytosis of IgG across epithelial cells is possible because FcRn binds IgG at acidic pH (<6.5) but not at neutral or higher pH.[6][7][16] The binding site for FcRn on IgG has been mapped using functional and structural studies, and involves in the interaction of relatively well conserved histidine residues on IgG with acidic residues on FcRn.[17] [18]

FcRn-mediated recycling and transcytosis of IgG and serum albumin Edit

FcRn extends the half-life of IgG and serum albumin by reducing lysosomal degradation of these proteins in endothelial cells[19] and bone-marrow derived cells.[20][21][22] The clearance rate of IgG and albumin is abnormally short in mice that lack functional FcRn.[9][10] IgG, serum albumin and other serum proteins are continuously internalized into cells through pinocytosis. Generally, internalized serum proteins are transported from early endosomes to lysosomes, where they are degraded. Following entry into cells, the two most abundant serum proteins, IgG and serum albumin, are bound by FcRn at the slightly acidic pH (<6.5) within early (sorting) endosomes, sorted and recycled to the cell surface where they are released at the neutral pH (>7.0) of the extracellular environment.[23][24][25] In this way, IgG and serum albumin are salvaged to avoid lysosomal degradation.[23][24][26] This cellular mechanism provides an explanation for the prolonged in vivo half-lives of IgG and serum albumin[12][13][23] and transport of these ligands across cellular barriers.[8][16][27] In addition, for cell types bathed in an acidic environment such as the slightly acidic intestinal lumen, cell surface FcRn can bind to IgG, transport bound ligand across intestinal epithelial cells followed by release at the near neutral pH at the basolateral surface.[6][7][16]

Diverse roles for FcRn in various organs Edit

FcRn is expressed on antigen-presenting leukocytes such as dendritic cells and is also expressed in neutrophils to help clear opsonized bacteria.[14] In the kidneys, FcRn is expressed on epithelial cells called podocytes to prevent IgG and albumin from clogging the glomerular filtration barrier.[28][29] Current studies are investigating FcRn in the liver because there are relatively low concentrations of both IgG and albumin in liver bile despite high concentrations in the blood.[30][31] Studies have also shown that FcRn-mediated transcytosis is involved with the trafficking of the HIV-1 virus across genital tract epithelium.[32]

Half-life extension of therapeutic proteins Edit

The identification of FcRn as a central regulator of IgG levels[9] led to the engineering of IgG-FcRn interactions to increase in vivo persistence of IgG.[11][33] For example, the half-life extended complement C5-specific antibody, Ultomiris (ravulizumab), has been approved for the treatment of autoimmunity[34] and a half-life extended antibody cocktail (Evusheld) with 'YTE' mutations[35] is used for the prophylaxis of SARS-CoV2.[36] Engineering of albumin-FcRn interactions has also generated albumin variants with increased in vivo half-lives.[37] It has also been shown that conjugation of some drugs to the Fc region of IgG or serum albumin to generate fusion proteins significantly increases their half-life.[38][39][40]

There are several drugs on the market that have Fc portions fused to the effector proteins in order to increase their half-lives through FcRn-mediated recycling. They include: Amevive (alefacept), Arcalyst (rilonacept), Enbrel (etanercept), Nplate (romiplostim), Orencia (abatacept) and Nulojix (belatacept).[40] Enbrel (etanercept) was the first successful IgG Fc-linked soluble receptor therapeutic and works by binding and neutralizing the pro-inflammatory cytokine, TNF-α.[40][41]

Targeting FcRn to treat autoimmune disease Edit

Multiple autoimmune disorders are caused by the binding of IgG to self antigens. Since FcRn extends IgG half-life in the circulation, it can also confer long half-lives on these pathogenic antibodies and promote autoimmune disease.[42][43][44] Therapies seek to disrupt the IgG-FcRn interaction to increase the clearance of disease-causing IgG autoantibodies from the body.[33] One such therapy is the infusion of intravenous immunoglobulin (IVIg) to saturate FcRn's IgG recycling capacity and proportionately reduce the levels of disease-causing IgG autoantibody binding to FcRn, thereby increasing disease-causing IgG autoantibody removal.[43][45][46] More recent approaches involve the strategy of blocking the binding of IgG to FcRn by delivering antibodies that bind with high affinity to this receptor through their Fc region[47][44][48] or variable regions.[49][50][51] These engineered Fc fragments or antibodies are being used in clinical trials as treatments for antibody-mediated autoimmune diseases such as primary immune thrombocytopenia and skin blistering diseases (pemphigus),[52][53][54][55] and the Fc-based inhibitor, efgartigimod, based on the 'Abdeg' technology[47] was recently approved (as 'Vyvgart') for the treatment of generalized myasthenia gravis in December 2021.[56]

References Edit

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Further reading Edit

  • Dürrbaum-Landmann I, Kaltenhäuser E, Flad HD, Ernst M (April 1994). "HIV-1 envelope protein gp120 affects phenotype and function of monocytes in vitro". Journal of Leukocyte Biology. 55 (4): 545–551. doi:10.1002/jlb.55.4.545. PMID 8145026. S2CID 44412688.
  • Leach JL, Sedmak DD, Osborne JM, Rahill B, Lairmore MD, Anderson CL (October 1996). "Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport". Journal of Immunology. 157 (8): 3317–3322. PMID 8871627.
  • Kivelä J, Parkkila S, Waheed A, Parkkila AK, Sly WS, Rajaniemi H (December 1997). "Secretory carbonic anhydrase isoenzyme (CA VI) in human serum". Clinical Chemistry. 43 (12): 2318–2322. doi:10.1093/clinchem/43.12.2318. PMID 9439449.
  • Vaughn DE, Bjorkman PJ (January 1998). "Structural basis of pH-dependent antibody binding by the neonatal Fc receptor". Structure. 6 (1): 63–73. doi:10.1016/S0969-2126(98)00008-2. PMID 9493268.
  • West AP, Bjorkman PJ (August 2000). "Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor(,)". Biochemistry. 39 (32): 9698–9708. doi:10.1021/bi000749m. PMID 10933786.
  • Mikulska JE, Pablo L, Canel J, Simister NE (August 2000). "Cloning and analysis of the gene encoding the human neonatal Fc receptor". European Journal of Immunogenetics. 27 (4): 231–240. doi:10.1046/j.1365-2370.2000.00225.x. PMID 10998088.
  • Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, et al. (March 2001). "MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells". Journal of Immunology. 166 (5): 3266–3276. doi:10.4049/jimmunol.166.5.3266. PMC 2827247. PMID 11207281.
  • Ober RJ, Radu CG, Ghetie V, Ward ES (December 2001). "Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies". International Immunology. 13 (12): 1551–1559. doi:10.1093/intimm/13.12.1551. PMID 11717196.
  • Praetor A, Hunziker W (June 2002). "beta(2)-Microglobulin is important for cell surface expression and pH-dependent IgG binding of human FcRn". Journal of Cell Science. 115 (Pt 11): 2389–2397. doi:10.1242/jcs.115.11.2389. PMID 12006623.
  • Claypool SM, Dickinson BL, Yoshida M, Lencer WI, Blumberg RS (August 2002). "Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin". The Journal of Biological Chemistry. 277 (31): 28038–28050. doi:10.1074/jbc.M202367200. PMC 2825174. PMID 12023961.
  • Praetor A, Jones RM, Wong WL, Hunziker W (August 2002). "Membrane-anchored human FcRn can oligomerize in the absence of IgG". Journal of Molecular Biology. 321 (2): 277–284. doi:10.1016/S0022-2836(02)00626-5. PMID 12144784.
  • Shah U, Dickinson BL, Blumberg RS, Simister NE, Lencer WI, Walker WA (February 2003). "Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine". Pediatric Research. 53 (2): 295–301. doi:10.1203/01.pdr.0000047663.81816.e3. PMC 2819091. PMID 12538789.
  • Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL (February 2003). "The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan". The Journal of Experimental Medicine. 197 (3): 315–322. doi:10.1084/jem.20021829. PMC 2193842. PMID 12566415.
  • Schilling R, Ijaz S, Davidoff M, Lee JY, Locarnini S, Williams R, Naoumov NV (August 2003). "Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions". Journal of Virology. 77 (16): 8882–8892. doi:10.1128/JVI.77.16.8882-8892.2003. PMC 167249. PMID 12885906.
  • Zhou J, Johnson JE, Ghetie V, Ober RJ, Ward ES (September 2003). "Generation of mutated variants of the human form of the MHC class I-related receptor, FcRn, with increased affinity for mouse immunoglobulin G". Journal of Molecular Biology. 332 (4): 901–913. doi:10.1016/S0022-2836(03)00952-5. PMID 12972260.
  • Cianga P, Cianga C, Cozma L, Ward ES, Carasevici E (December 2003). "The MHC class I related Fc receptor, FcRn, is expressed in the epithelial cells of the human mammary gland". Human Immunology. 64 (12): 1152–1159. doi:10.1016/j.humimm.2003.08.025. PMID 14630397.
  • Ober RJ, Martinez C, Vaccaro C, Zhou J, Ward ES (February 2004). "Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn". Journal of Immunology. 172 (4): 2021–2029. doi:10.4049/jimmunol.172.4.2021. PMID 14764666.

External links Edit

August 28, 2023
neonatal, receptor, neonatal, receptor, also, fcrn, receptor, fcrn, large, subunit, brambell, receptor, protein, that, humans, encoded, fcgrt, gene, receptor, which, similar, structure, class, molecule, also, associates, with, beta, microglobulin, rodents, fcr. The neonatal Fc receptor also FcRn IgG receptor FcRn large subunit p51 or Brambell receptor is a protein that in humans is encoded by the FCGRT gene 1 2 3 It is an IgG Fc receptor which is similar in structure to the MHC class I molecule and also associates with beta 2 microglobulin 4 5 In rodents FcRn was originally identified as the receptor that transports maternal immunoglobulin G IgG from mother to neonatal offspring via mother s milk leading to its name as the neonatal Fc receptor 6 7 In humans FcRn is present in the placenta where it transports mother s IgG to the growing fetus 1 8 FcRn has also been shown to play a role in regulating IgG and serum albumin turnover 9 10 11 12 13 Neonatal Fc receptor expression is up regulated by the proinflammatory cytokine TNF and down regulated by IFN g 14 Fc fragment of IgG receptor transporter alphaIdentifiersSymbolFCGRTNCBI gene2217HGNC3621OMIM601437RefSeqNM 004107UniProtP55899Other dataLocusChr 19 q13 3Search forStructuresSwiss modelDomainsInterPro Contents 1 Interactions of FcRn with IgG and serum albumin 2 FcRn mediated recycling and transcytosis of IgG and serum albumin 3 Diverse roles for FcRn in various organs 4 Half life extension of therapeutic proteins 5 Targeting FcRn to treat autoimmune disease 6 References 7 Further reading 8 External linksInteractions of FcRn with IgG and serum albumin EditIn addition to binding to IgG FCGRT has been shown to interact with human serum albumin 10 15 FcRn mediated transcytosis of IgG across epithelial cells is possible because FcRn binds IgG at acidic pH lt 6 5 but not at neutral or higher pH 6 7 16 The binding site for FcRn on IgG has been mapped using functional and structural studies and involves in the interaction of relatively well conserved histidine residues on IgG with acidic residues on FcRn 17 18 FcRn mediated recycling and transcytosis of IgG and serum albumin EditFcRn extends the half life of IgG and serum albumin by reducing lysosomal degradation of these proteins in endothelial cells 19 and bone marrow derived cells 20 21 22 The clearance rate of IgG and albumin is abnormally short in mice that lack functional FcRn 9 10 IgG serum albumin and other serum proteins are continuously internalized into cells through pinocytosis Generally internalized serum proteins are transported from early endosomes to lysosomes where they are degraded Following entry into cells the two most abundant serum proteins IgG and serum albumin are bound by FcRn at the slightly acidic pH lt 6 5 within early sorting endosomes sorted and recycled to the cell surface where they are released at the neutral pH gt 7 0 of the extracellular environment 23 24 25 In this way IgG and serum albumin are salvaged to avoid lysosomal degradation 23 24 26 This cellular mechanism provides an explanation for the prolonged in vivo half lives of IgG and serum albumin 12 13 23 and transport of these ligands across cellular barriers 8 16 27 In addition for cell types bathed in an acidic environment such as the slightly acidic intestinal lumen cell surface FcRn can bind to IgG transport bound ligand across intestinal epithelial cells followed by release at the near neutral pH at the basolateral surface 6 7 16 Diverse roles for FcRn in various organs EditFcRn is expressed on antigen presenting leukocytes such as dendritic cells and is also expressed in neutrophils to help clear opsonized bacteria 14 In the kidneys FcRn is expressed on epithelial cells called podocytes to prevent IgG and albumin from clogging the glomerular filtration barrier 28 29 Current studies are investigating FcRn in the liver because there are relatively low concentrations of both IgG and albumin in liver bile despite high concentrations in the blood 30 31 Studies have also shown that FcRn mediated transcytosis is involved with the trafficking of the HIV 1 virus across genital tract epithelium 32 Half life extension of therapeutic proteins EditThe identification of FcRn as a central regulator of IgG levels 9 led to the engineering of IgG FcRn interactions to increase in vivo persistence of IgG 11 33 For example the half life extended complement C5 specific antibody Ultomiris ravulizumab has been approved for the treatment of autoimmunity 34 and a half life extended antibody cocktail Evusheld with YTE mutations 35 is used for the prophylaxis of SARS CoV2 36 Engineering of albumin FcRn interactions has also generated albumin variants with increased in vivo half lives 37 It has also been shown that conjugation of some drugs to the Fc region of IgG or serum albumin to generate fusion proteins significantly increases their half life 38 39 40 There are several drugs on the market that have Fc portions fused to the effector proteins in order to increase their half lives through FcRn mediated recycling They include Amevive alefacept Arcalyst rilonacept Enbrel etanercept Nplate romiplostim Orencia abatacept and Nulojix belatacept 40 Enbrel etanercept was the first successful IgG Fc linked soluble receptor therapeutic and works by binding and neutralizing the pro inflammatory cytokine TNF a 40 41 Targeting FcRn to treat autoimmune disease EditMultiple autoimmune disorders are caused by the binding of IgG to self antigens Since FcRn extends IgG half life in the circulation it can also confer long half lives on these pathogenic antibodies and promote autoimmune disease 42 43 44 Therapies seek to disrupt the IgG FcRn interaction to increase the clearance of disease causing IgG autoantibodies from the body 33 One such therapy is the infusion of intravenous immunoglobulin IVIg to saturate FcRn s IgG recycling capacity and proportionately reduce the levels of disease causing IgG autoantibody binding to FcRn thereby increasing disease causing IgG autoantibody removal 43 45 46 More recent approaches involve the strategy of blocking the binding of IgG to FcRn by delivering antibodies that bind with high affinity to this receptor through their Fc region 47 44 48 or variable regions 49 50 51 These engineered Fc fragments or antibodies are being used in clinical trials as treatments for antibody mediated autoimmune diseases such as primary immune thrombocytopenia and skin blistering diseases pemphigus 52 53 54 55 and the Fc based inhibitor efgartigimod based on the Abdeg technology 47 was recently approved as Vyvgart for the treatment of generalized myasthenia gravis in December 2021 56 References Edit a b Story CM Mikulska JE Simister NE December 1994 A major histocompatibility complex class I like Fc receptor cloned from human placenta possible role in transfer of immunoglobulin G from mother to fetus The Journal of Experimental Medicine 180 6 2377 2381 doi 10 1084 jem 180 6 2377 PMC 2191771 PMID 7964511 Kandil E Egashira M Miyoshi O Niikawa N Ishibashi T Kasahara M Miyosi O July 1996 The human gene encoding the heavy chain of the major histocompatibility complex class I like Fc receptor FCGRT maps to 19q13 3 Cytogenetics and Cell Genetics 73 1 2 97 98 doi 10 1159 000134316 PMID 8646894 Entrez Gene FCGRT Fc fragment of IgG receptor transporter alpha Simister NE Mostov KE 1989 Cloning and expression of the neonatal rat intestinal Fc receptor a major histocompatibility complex class I antigen homolog Cold Spring Harbor Symposia on Quantitative Biology 54 Pt 1 571 580 doi 10 1101 sqb 1989 054 01 068 PMID 2534798 Kuo TT Aveson VG 2011 01 01 Neonatal Fc receptor and IgG based therapeutics mAbs 3 5 422 430 doi 10 4161 mabs 3 5 16983 PMC 3225846 PMID 22048693 a b c Rodewald R Kraehenbuhl JP July 1984 Receptor mediated transport of IgG The Journal of Cell Biology 99 1 Pt 2 159s 164s doi 10 1083 jcb 99 1 159s PMC 2275593 PMID 6235233 a b c Simister NE Rees AR July 1985 Isolation and characterization of an Fc receptor from neonatal rat small intestine European Journal of Immunology 15 7 733 738 doi 10 1002 eji 1830150718 PMID 2988974 S2CID 42396197 a b Firan M Bawdon R Radu C Ober RJ Eaken D Antohe F et al August 2001 The MHC class I related receptor FcRn plays an essential role in the maternofetal transfer of gamma globulin in humans International Immunology 13 8 993 1002 doi 10 1093 intimm 13 8 993 PMID 11470769 a b c Ghetie V Hubbard JG Kim JK Tsen MF Lee Y Ward ES March 1996 Abnormally short serum half lives of IgG in beta 2 microglobulin deficient mice European Journal of Immunology 26 3 690 696 doi 10 1002 eji 1830260327 PMID 8605939 S2CID 85730132 a b c Chaudhury C Mehnaz S Robinson JM Hayton WL Pearl DK Roopenian DC Anderson CL February 2003 The major histocompatibility complex related Fc receptor for IgG FcRn binds albumin and prolongs its lifespan The Journal of Experimental Medicine 197 3 315 322 doi 10 1084 jem 20021829 PMC 2193842 PMID 12566415 a b Ghetie V Popov S Borvak J Radu C Matesoi D Medesan C et al July 1997 Increasing the serum persistence of an IgG fragment by random mutagenesis Nature Biotechnology 15 7 637 640 doi 10 1038 nbt0797 637 PMID 9219265 S2CID 39836528 a b Roopenian DC Akilesh S September 2007 FcRn the neonatal Fc receptor comes of age Nature Reviews Immunology 7 9 715 725 doi 10 1038 nri2155 PMID 17703228 S2CID 6980400 a b Ward ES Ober RJ 2009 Chapter 4 Multitasking by exploitation of intracellular transport functions the many faces of FcRn Advances in Immunology 103 77 115 doi 10 1016 S0065 2776 09 03004 1 PMC 4485553 PMID 19755184 a b Kuo TT Baker K Yoshida M Qiao SW Aveson VG Lencer WI Blumberg RS November 2010 Neonatal Fc receptor from immunity to therapeutics Journal of Clinical Immunology 30 6 777 789 doi 10 1007 s10875 010 9468 4 PMC 2970823 PMID 20886282 Andersen JT Dee Qian J Sandlie I November 2006 The conserved histidine 166 residue of the human neonatal Fc receptor heavy chain is critical for the pH dependent binding to albumin European Journal of Immunology 36 11 3044 3051 doi 10 1002 eji 200636556 PMID 17048273 S2CID 22024929 a b c Dickinson BL Badizadegan K Wu Z Ahouse JC Zhu X Simister NE et al October 1999 Bidirectional FcRn dependent IgG transport in a polarized human intestinal epithelial cell line The Journal of Clinical Investigation 104 7 903 911 doi 10 1172 JCI6968 PMC 408555 PMID 10510331 Kim JK Tsen MF Ghetie V Ward ES October 1994 Localization of the site of the murine IgG1 molecule that is involved in binding to the murine intestinal Fc receptor European Journal of Immunology 24 10 2429 2434 doi 10 1002 eji 1830241025 PMID 7925571 S2CID 43499403 Martin WL West AP Gan L Bjorkman PJ April 2001 Crystal structure at 2 8 A of an FcRn heterodimeric Fc complex mechanism of pH dependent binding Molecular Cell 7 4 867 877 doi 10 1016 s1097 2765 01 00230 1 PMID 11336709 Ward ES Zhou J Ghetie V Ober RJ February 2003 Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans International Immunology 15 2 187 195 doi 10 1093 intimm dxg018 PMID 12578848 Akilesh S Christianson GJ Roopenian DC Shaw AS October 2007 Neonatal FcR expression in bone marrow derived cells functions to protect serum IgG from catabolism Journal of Immunology 179 7 4580 4588 doi 10 4049 jimmunol 179 7 4580 PMID 17878355 Qiao SW Kobayashi K Johansen FE Sollid LM Andersen JT Milford E et al July 2008 Dependence of antibody mediated presentation of antigen on FcRn Proceedings of the National Academy of Sciences of the United States of America 105 27 9337 9342 Bibcode 2008PNAS 105 9337Q doi 10 1073 pnas 0801717105 PMC 2453734 PMID 18599440 Montoyo HP Vaccaro C Hafner M Ober RJ Mueller W Ward ES February 2009 Conditional deletion of the MHC class I related receptor FcRn reveals the sites of IgG homeostasis in mice Proceedings of the National Academy of Sciences of the United States of America 106 8 2788 2793 Bibcode 2009PNAS 106 2788M doi 10 1073 pnas 0810796106 PMC 2650344 PMID 19188594 a b c Ober RJ Martinez C Vaccaro C Zhou J Ward ES February 2004 Visualizing the site and dynamics of IgG salvage by the MHC class I related receptor FcRn Journal of Immunology 172 4 2021 2029 doi 10 4049 jimmunol 172 4 2021 PMID 14764666 S2CID 30526875 a b Ober RJ Martinez C Lai X Zhou J Ward ES July 2004 Exocytosis of IgG as mediated by the receptor FcRn an analysis at the single molecule level Proceedings of the National Academy of Sciences of the United States of America 101 30 11076 11081 Bibcode 2004PNAS 10111076O doi 10 1073 pnas 0402970101 PMC 503743 PMID 15258288 Prabhat P Gan Z Chao J Ram S Vaccaro C Gibbons S et al April 2007 Elucidation of intracellular recycling pathways leading to exocytosis of the Fc receptor FcRn by using multifocal plane microscopy Proceedings of the National Academy of Sciences of the United States of America 104 14 5889 5894 doi 10 1073 pnas 0700337104 PMC 1851587 PMID 17384151 Larsen MT Rawsthorne H Schelde KK Dagnaes Hansen F Cameron J Howard KA October 2018 Cellular recycling driven in vivo half life extension using recombinant albumin fusions tuned for neonatal Fc receptor FcRn engagement Journal of Controlled Release 287 132 141 doi 10 1016 j jconrel 2018 07 023 PMID 30016735 S2CID 51677989 Spiekermann GM Finn PW Ward ES Dumont J Dickinson BL Blumberg RS Lencer WI August 2002 Receptor mediated immunoglobulin G transport across mucosal barriers in adult life functional expression of FcRn in the mammalian lung The Journal of Experimental Medicine 196 3 303 310 doi 10 1084 jem 20020400 PMC 2193935 PMID 12163559 Akilesh S Huber TB Wu H Wang G Hartleben B Kopp JB et al January 2008 Podocytes use FcRn to clear IgG from the glomerular basement membrane Proceedings of the National Academy of Sciences of the United States of America 105 3 967 972 doi 10 1073 pnas 0711515105 PMC 2242706 PMID 18198272 Bern M Sand KM Nilsen J Sandlie I Andersen JT August 2015 The role of albumin receptors in regulation of albumin homeostasis Implications for drug delivery Journal of Controlled Release 211 144 162 doi 10 1016 j jconrel 2015 06 006 PMID 26055641 Sand KM Bern M Nilsen J Noordzij HT Sandlie I Andersen JT 2015 01 26 Unraveling the Interaction between FcRn and Albumin Opportunities for Design of Albumin Based Therapeutics Frontiers in Immunology 5 682 doi 10 3389 fimmu 2014 00682 PMC 4306297 PMID 25674083 Pyzik M Rath T Kuo TT Win S Baker K Hubbard JJ et al April 2017 Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury Proceedings of the National Academy of Sciences of the United States of America 114 14 E2862 E2871 doi 10 1073 pnas 1618291114 PMC 5389309 PMID 28330995 Gupta S Gach JS Becerra JC Phan TB Pudney J Moldoveanu Z et al 2013 11 01 The Neonatal Fc receptor FcRn enhances human immunodeficiency virus type 1 HIV 1 transcytosis across epithelial cells PLOS Pathogens 9 11 e1003776 doi 10 1371 journal ppat 1003776 PMC 3836734 PMID 24278022 a b Ward ES Ober RJ October 2018 Targeting FcRn to Generate Antibody Based Therapeutics Trends in Pharmacological Sciences 39 10 892 904 doi 10 1016 j tips 2018 07 007 PMC 6169532 PMID 30143244 Ultomiris ravulizumab cwvz Alexion Retrieved 2021 10 03 Dall Acqua WF Woods RM Ward ES Palaszynski SR Patel NK Brewah YA et al November 2002 Increasing the affinity of a human IgG1 for the neonatal Fc receptor biological consequences Journal of Immunology 169 9 5171 5180 doi 10 4049 jimmunol 169 9 5171 PMID 12391234 S2CID 29398244 Coronavirus COVID 19 Update FDA Authorizes New Long Acting Monoclonal Antibodies for Pre exposure Prevention of COVID 19 in Certain Individuals U S Food and Drug Administration 8 December 2021 Andersen JT Dalhus B Viuff D Ravn BT Gunnarsen KS Plumridge A et al May 2014 Extending serum half life of albumin by engineering neonatal Fc receptor FcRn binding The Journal of Biological Chemistry 289 19 13492 13502 doi 10 1074 jbc M114 549832 PMC 4036356 PMID 24652290 Lee TY Tjin Tham Sjin RM Movahedi S Ahmed B Pravda EA Lo KM et al March 2008 Linking antibody Fc domain to endostatin significantly improves endostatin half life and efficacy Clinical Cancer Research 14 5 1487 1493 doi 10 1158 1078 0432 CCR 07 1530 PMID 18316573 Poznansky MJ Halford J Taylor D October 1988 Growth hormone albumin conjugates Reduced renal toxicity and altered plasma clearance FEBS Letters 239 1 18 22 doi 10 1016 0014 5793 88 80537 4 PMID 3181423 S2CID 38592689 a b c Strohl WR August 2015 Fusion Proteins for Half Life Extension of Biologics as a Strategy to Make Biobetters BioDrugs 29 4 215 239 doi 10 1007 s40259 015 0133 6 PMC 4562006 PMID 26177629 Goldenberg MM January 1999 Etanercept a novel drug for the treatment of patients with severe active rheumatoid arthritis Clinical Therapeutics 21 1 75 87 discussion 1 2 doi 10 1016 S0149 2918 00 88269 7 PMID 10090426 Akilesh S Petkova S Sproule TJ Shaffer DJ Christianson GJ Roopenian D May 2004 The MHC class I like Fc receptor promotes humorally mediated autoimmune disease The Journal of Clinical Investigation 113 9 1328 1333 doi 10 1172 JCI18838 PMC 398424 PMID 15124024 a b Hansen RJ Balthasar JP June 2003 Pharmacokinetic pharmacodynamic modeling of the effects of intravenous immunoglobulin on the disposition of antiplatelet antibodies in a rat model of immune thrombocytopenia Journal of Pharmaceutical Sciences 92 6 1206 1215 doi 10 1002 jps 10364 PMID 12761810 a b Patel DA Puig Canto A Challa DK Perez Montoyo H Ober RJ Ward ES July 2011 Neonatal Fc receptor blockade by Fc engineering ameliorates arthritis in a murine model Journal of Immunology 187 2 1015 1022 doi 10 4049 jimmunol 1003780 PMC 3157913 PMID 21690327 Sockolosky JT Szoka FC August 2015 The neonatal Fc receptor FcRn as a target for drug delivery and therapy Advanced Drug Delivery Reviews Editor s Collection 2015 91 109 124 doi 10 1016 j addr 2015 02 005 PMC 4544678 PMID 25703189 Nimmerjahn F Ravetch JV 2008 01 01 Anti inflammatory actions of intravenous immunoglobulin Annual Review of Immunology 26 1 513 533 doi 10 1146 annurev immunol 26 021607 090232 PMID 18370923 a b Vaccaro C Zhou J Ober RJ Ward ES October 2005 Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels Nature Biotechnology 23 10 1283 1288 doi 10 1038 nbt1143 PMID 16186811 S2CID 13526188 Ulrichts P Guglietta A Dreier T van Bragt T Hanssens V Hofman E et al October 2018 Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans The Journal of Clinical Investigation 128 10 4372 4386 doi 10 1172 JCI97911 PMC 6159959 PMID 30040076 Nixon AE Chen J Sexton DJ Muruganandam A Bitonti AJ Dumont J et al 2015 Fully human monoclonal antibody inhibitors of the neonatal fc receptor reduce circulating IgG in non human primates Frontiers in Immunology 6 176 doi 10 3389 fimmu 2015 00176 PMC 4407741 PMID 25954273 Kiessling P Lledo Garcia R Watanabe S Langdon G Tran D Bari M et al November 2017 The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration A randomized phase 1 study Science Translational Medicine 9 414 eaan1208 doi 10 1126 scitranslmed aan1208 PMID 29093180 S2CID 206694327 Blumberg LJ Humphries JE Jones SD Pearce LB Holgate R Hearn A et al December 2019 Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex mediated immune responses Science Advances 5 12 eaax9586 Bibcode 2019SciA 5 9586B doi 10 1126 sciadv aax9586 PMC 6920022 PMID 31897428 Newland AC Sanchez Gonzalez B Rejto L Egyed M Romanyuk N Godar M et al February 2020 Phase 2 study of efgartigimod a novel FcRn antagonist in adult patients with primary immune thrombocytopenia American Journal of Hematology 95 2 178 187 doi 10 1002 ajh 25680 PMC 7004056 PMID 31821591 Robak T Kazmierczak M Jarque I Musteata V Trelinski J Cooper N et al September 2020 Phase 2 multiple dose study of an FcRn inhibitor rozanolixizumab in patients with primary immune thrombocytopenia Blood Advances 4 17 4136 4146 doi 10 1182 bloodadvances 2020002003 PMC 7479959 PMID 32886753 Werth VP Culton DA Concha JS Graydon JS Blumberg LJ Okawa J et al December 2021 Safety Tolerability and Activity of ALXN1830 Targeting the Neonatal Fc Receptor in Chronic Pemphigus The Journal of Investigative Dermatology 141 12 2858 2865 e4 doi 10 1016 j jid 2021 04 031 PMID 34126109 S2CID 235439165 Goebeler M Bata Csorgo Z De Simone C Didona B Remenyik E Reznichenko N et al October 2021 Treatment of pemphigus vulgaris and foliaceus with efgartigimod a neonatal Fc receptor inhibitor a phase II multicentre open label feasibility trial The British Journal of Dermatology 186 3 429 439 doi 10 1111 bjd 20782 PMID 34608631 S2CID 238355823 argenx Announces U S Food and Drug Administration FDA Approval of VYVGART efgartigimod alfa fcab in Generalized Myasthenia Gravis Argenx 17 December 2021 Further reading EditDurrbaum Landmann I Kaltenhauser E Flad HD Ernst M April 1994 HIV 1 envelope protein gp120 affects phenotype and function of monocytes in vitro Journal of Leukocyte Biology 55 4 545 551 doi 10 1002 jlb 55 4 545 PMID 8145026 S2CID 44412688 Leach JL Sedmak DD Osborne JM Rahill B Lairmore MD Anderson CL October 1996 Isolation from human placenta of the IgG transporter FcRn and localization to the syncytiotrophoblast implications for maternal fetal antibody transport Journal of Immunology 157 8 3317 3322 PMID 8871627 Kivela J Parkkila S Waheed A Parkkila AK Sly WS Rajaniemi H December 1997 Secretory carbonic anhydrase isoenzyme CA VI in human serum Clinical Chemistry 43 12 2318 2322 doi 10 1093 clinchem 43 12 2318 PMID 9439449 Vaughn DE Bjorkman PJ January 1998 Structural basis of pH dependent antibody binding by the neonatal Fc receptor Structure 6 1 63 73 doi 10 1016 S0969 2126 98 00008 2 PMID 9493268 West AP Bjorkman PJ August 2000 Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex related Fc receptor Biochemistry 39 32 9698 9708 doi 10 1021 bi000749m PMID 10933786 Mikulska JE Pablo L Canel J Simister NE August 2000 Cloning and analysis of the gene encoding the human neonatal Fc receptor European Journal of Immunogenetics 27 4 231 240 doi 10 1046 j 1365 2370 2000 00225 x PMID 10998088 Zhu X Meng G Dickinson BL Li X Mizoguchi E Miao L et al March 2001 MHC class I related neonatal Fc receptor for IgG is functionally expressed in monocytes intestinal macrophages and dendritic cells Journal of Immunology 166 5 3266 3276 doi 10 4049 jimmunol 166 5 3266 PMC 2827247 PMID 11207281 Ober RJ Radu CG Ghetie V Ward ES December 2001 Differences in promiscuity for antibody FcRn interactions across species implications for therapeutic antibodies International Immunology 13 12 1551 1559 doi 10 1093 intimm 13 12 1551 PMID 11717196 Praetor A Hunziker W June 2002 beta 2 Microglobulin is important for cell surface expression and pH dependent IgG binding of human FcRn Journal of Cell Science 115 Pt 11 2389 2397 doi 10 1242 jcs 115 11 2389 PMID 12006623 Claypool SM Dickinson BL Yoshida M Lencer WI Blumberg RS August 2002 Functional reconstitution of human FcRn in Madin Darby canine kidney cells requires co expressed human beta 2 microglobulin The Journal of Biological Chemistry 277 31 28038 28050 doi 10 1074 jbc M202367200 PMC 2825174 PMID 12023961 Praetor A Jones RM Wong WL Hunziker W August 2002 Membrane anchored human FcRn can oligomerize in the absence of IgG Journal of Molecular Biology 321 2 277 284 doi 10 1016 S0022 2836 02 00626 5 PMID 12144784 Shah U Dickinson BL Blumberg RS Simister NE Lencer WI Walker WA February 2003 Distribution of the IgG Fc receptor FcRn in the human fetal intestine Pediatric Research 53 2 295 301 doi 10 1203 01 pdr 0000047663 81816 e3 PMC 2819091 PMID 12538789 Chaudhury C Mehnaz S Robinson JM Hayton WL Pearl DK Roopenian DC Anderson CL February 2003 The major histocompatibility complex related Fc receptor for IgG FcRn binds albumin and prolongs its lifespan The Journal of Experimental Medicine 197 3 315 322 doi 10 1084 jem 20021829 PMC 2193842 PMID 12566415 Schilling R Ijaz S Davidoff M Lee JY Locarnini S Williams R Naoumov NV August 2003 Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions Journal of Virology 77 16 8882 8892 doi 10 1128 JVI 77 16 8882 8892 2003 PMC 167249 PMID 12885906 Zhou J Johnson JE Ghetie V Ober RJ Ward ES September 2003 Generation of mutated variants of the human form of the MHC class I related receptor FcRn with increased affinity for mouse immunoglobulin G Journal of Molecular Biology 332 4 901 913 doi 10 1016 S0022 2836 03 00952 5 PMID 12972260 Cianga P Cianga C Cozma L Ward ES Carasevici E December 2003 The MHC class I related Fc receptor FcRn is expressed in the epithelial cells of the human mammary gland Human Immunology 64 12 1152 1159 doi 10 1016 j humimm 2003 08 025 PMID 14630397 Ober RJ Martinez C Vaccaro C Zhou J Ward ES February 2004 Visualizing the site and dynamics of IgG salvage by the MHC class I related receptor FcRn Journal of Immunology 172 4 2021 2029 doi 10 4049 jimmunol 172 4 2021 PMID 14764666 External links Editneonatal Fc receptor at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Neonatal Fc receptor amp oldid 1170301190, wikipedia, wiki, book, books, library,

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