Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors

Introduction of heterologous anti–glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production of IgG anti-NTS antibodies that are predominantly IgG2b and the glomerular deposition of pathogenic immune complexes, leading to accelerated renal disease...

Full description

Bibliographic Details
Main Authors:	Kaneko, Yoshikatsu, Nimmerjahn, Falk, Madaio, Michael P., Ravetch, Jeffrey V.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118246/

id	pubmed-2118246
recordtype	oai_dc
spelling	pubmed-21182462007-12-13 Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors Kaneko, Yoshikatsu Nimmerjahn, Falk Madaio, Michael P. Ravetch, Jeffrey V. Articles Introduction of heterologous anti–glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production of IgG anti-NTS antibodies that are predominantly IgG2b and the glomerular deposition of pathogenic immune complexes, leading to accelerated renal disease. The pathology observed in this model is determined by the effector cell activation threshold that is established by the coexpression on infiltrating macrophages of the IgG2a/2b restricted activation receptor FcγRIV and its inhibitory receptor counterpart, FcγRIIB. Blocking FcγRIV with a specific monoclonal antibody thereby preventing IgG2b engagement or treatment with high dose intravenous γ-globulin (IVIG) to down-regulate FcγRIV while up-regulating FcγRIIB, protects mice from fatal disease. In the absence of FcγRIIB, IVIG is not protective; this indicates that reduced FcγRIV expression alone is insufficient to protect animals from pathogenic IgG2b immune complexes. These results establish the significance of specific IgG subclasses and their cognate FcγRs in renal disease. The Rockefeller University Press 2006-03-20 /pmc/articles/PMC2118246/ /pubmed/16520389 http://dx.doi.org/10.1084/jem.20051900 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kaneko, Yoshikatsu Nimmerjahn, Falk Madaio, Michael P. Ravetch, Jeffrey V.
spellingShingle	Kaneko, Yoshikatsu Nimmerjahn, Falk Madaio, Michael P. Ravetch, Jeffrey V. Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
author_facet	Kaneko, Yoshikatsu Nimmerjahn, Falk Madaio, Michael P. Ravetch, Jeffrey V.
author_sort	Kaneko, Yoshikatsu
title	Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
title_short	Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
title_full	Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
title_fullStr	Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
title_full_unstemmed	Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
title_sort	pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific fc receptors
description	Introduction of heterologous anti–glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production of IgG anti-NTS antibodies that are predominantly IgG2b and the glomerular deposition of pathogenic immune complexes, leading to accelerated renal disease. The pathology observed in this model is determined by the effector cell activation threshold that is established by the coexpression on infiltrating macrophages of the IgG2a/2b restricted activation receptor FcγRIV and its inhibitory receptor counterpart, FcγRIIB. Blocking FcγRIV with a specific monoclonal antibody thereby preventing IgG2b engagement or treatment with high dose intravenous γ-globulin (IVIG) to down-regulate FcγRIV while up-regulating FcγRIIB, protects mice from fatal disease. In the absence of FcγRIIB, IVIG is not protective; this indicates that reduced FcγRIV expression alone is insufficient to protect animals from pathogenic IgG2b immune complexes. These results establish the significance of specific IgG subclasses and their cognate FcγRs in renal disease.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118246/
_version_	1611414646869196800

Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors

Similar Items