Neonatal Fc receptor promotes immune complex-mediated glomerular disease

Journal of the American Society of Nephrology : JASN
Florina OlaruDorin-Bogdan Borza

Abstract

The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex-mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex-mediated glomerular diseases. As proof of ...Continue Reading

References

Jan 15, 2002·American Journal of Physiology. Renal Physiology·Noriyoshi KobayashiYasuhiko Tomino
Jun 28, 2002·The New England Journal of Medicine·Hanna DebiecPierre M Ronco
Feb 5, 2003·The Journal of Experimental Medicine·Chaity ChaudhuryClark L Anderson
May 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Helmut HopferRaghu Kalluri
Nov 13, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Maria KoltunWayne D Comper
Apr 1, 2005·Journal of the American Society of Nephrology : JASN·Patrick N Cunningham, Richard J Quigg
Nov 15, 2005·The Journal of Clinical Investigation·Ning LiZhi Liu
Aug 11, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Joëlle L NortierPierre Ronco
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Liming LiuAlan Bitonti
Aug 19, 2007·Nature Reviews. Immunology·Derry C Roopenian, Shreeram Akilesh
Jan 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shreeram AkileshAndrey S Shaw
Feb 1, 2008·Journal of the American Society of Nephrology : JASN·Corina M BorzaBilly G Hudson
Feb 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Adam R MezoAlan J Bitonti
Jun 11, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alina SesarmanCassian Sitaru
Jul 3, 2009·The New England Journal of Medicine·Laurence H BeckDavid J Salant
Aug 8, 2009·Journal of the American Society of Nephrology : JASN·Menaka SaravRichard J Quigg
Aug 17, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wentian LuoDorin-Bogdan Borza
Dec 15, 2010·Neuron·Adish DaniXiaowei Zhuang
Jun 3, 2011·The New England Journal of Medicine·Hanna DebiecPierre Ronco
Jun 22, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dipesh A PatelE Sally Ward
Jul 26, 2011·Journal of the American Society of Nephrology : JASN·Laurence H BeckDavid J Salant
Dec 24, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Carsten SteinBirgit Rathkolb
Mar 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jun-Jun ZhangDorin-Bogdan Borza
Mar 23, 2012·Kidney International·Helmut HopferHans-Willi Mittrücker
Jan 11, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florina OlaruDorin-Bogdan Borza

❮ Previous
Next ❯

Citations

Jul 5, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Bonny L Dickinson
Mar 25, 2018·Scientific Reports·Johan SeijsingTorbjörn Gräslund
Dec 19, 2018·Current Opinion in Rheumatology·Rhea Bhargava, George C Tsokos
Sep 26, 2019·American Journal of Physiology. Cell Physiology·Pantipa TonsawanJudith Blaine
Jul 30, 2019·Frontiers in Immunology·Michal PyzikRichard S Blumberg
May 17, 2017·CEN Case Reports·Misa IkedaTakanori Shibata
Mar 30, 2016·Current Opinion in Nephrology and Hypertension·Alfred H J KimAndrey S Shaw
Jul 1, 2017·Frontiers in Medicine·Christos P ArgyropoulosAntonios H Tzamaloukas
Sep 9, 2020·The Journal of Allergy and Clinical Immunology·Dhavalkumar D Patel, James B Bussel
Apr 4, 2021·International Journal of Molecular Sciences·Timothy Qi, Yanguang Cao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Basement Membranes

Basement membranes are thin, specialized extracellular matrices surrounding most tissues in all metazoans. Here is the latest research on basement membranes.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jun-Jun ZhangDorin-Bogdan Borza
Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Alina SesarmanCassian Sitaru
Clinical Journal of the American Society of Nephrology : CJASN
Jun-liang ChenMing-hui Zhao
© 2021 Meta ULC. All rights reserved