IgG1 protects against renal disease in a mouse model of cryoglobulinaemia

Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pa...
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Autor*in:	Richard T Strait [verfasserIn] Monica T Posgai Ashley Mahler Nathaniel Barasa Chaim O Jacob Jörg Köhl Marc Ehlers Keith Stringer Shiva Kumar Shanmukhappa David Witte Md Monir Hossain Marat Khodoun Andrew B Herr Fred D Finkelman

Format:	Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology

Übergeordnetes Werk:	Enthalten in: Nature - London : Macmillan Publishers Limited, part of Springer Nature, 1869, 517(2015), 7535, Seite 501-504
Übergeordnetes Werk:	volume:517 ; year:2015 ; number:7535 ; pages:501-504

Links:	Volltext Link aufrufen Link aufrufen

DOI / URN:	10.1038/nature13868

Katalog-ID:	OLC1962476901

Internformat


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520			\|a Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology.
650		4	\|a Kidney diseases
650		4	\|a Immune system
650		4	\|a Medical research
650		4	\|a Rodents
650		4	\|a Cryoglobulinemia - immunology
650		4	\|a Antigen-Antibody Complex - chemistry
650		4	\|a Glomerulonephritis - etiology
650		4	\|a Antibodies, Monoclonal - immunology
650		4	\|a Antigen-Antibody Complex - immunology
650		4	\|a Glomerulonephritis - immunology
650		4	\|a Cryoglobulinemia - pathology
650		4	\|a Immunoglobulin G - immunology
650		4	\|a Cryoglobulinemia - complications
650		4	\|a Trinitrobenzenes - immunology
650		4	\|a Antigens - immunology
650		4	\|a Glomerulonephritis - prevention & control
650		4	\|a Glomerulonephritis - pathology
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700	0		\|a Chaim O Jacob \|4 oth
700	0		\|a Jörg Köhl \|4 oth
700	0		\|a Marc Ehlers \|4 oth
700	0		\|a Keith Stringer \|4 oth
700	0		\|a Shiva Kumar Shanmukhappa \|4 oth
700	0		\|a David Witte \|4 oth
700	0		\|a Md Monir Hossain \|4 oth
700	0		\|a Marat Khodoun \|4 oth
700	0		\|a Andrew B Herr \|4 oth
700	0		\|a Fred D Finkelman \|4 oth
773	0	8	\|i Enthalten in \|t Nature \|d London : Macmillan Publishers Limited, part of Springer Nature, 1869 \|g 517(2015), 7535, Seite 501-504 \|w (DE-627)129292834 \|w (DE-600)120714-3 \|w (DE-576)014473941 \|x 0028-0836 \|7 nnns
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856	4	1	\|u http://dx.doi.org/10.1038/nature13868 \|3 Volltext
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matchkey_str	article:00280836:2015----::g1rtcsgisrnliesiaosmdl
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publishDate	2015
allfields	10.1038/nature13868 doi PQ20160617 (DE-627)OLC1962476901 (DE-599)GBVOLC1962476901 (PRQ)c2288-c2e2a7b350510209b32cdfd82624a367579af8fb2f8c8094c092f653df777fab0 (KEY)0072945020150000517753500501igg1protectsagainstrenaldiseaseinamousemodelofcryo DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Richard T Strait verfasserin aut IgG1 protects against renal disease in a mouse model of cryoglobulinaemia 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology. Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology Monica T Posgai oth Ashley Mahler oth Nathaniel Barasa oth Chaim O Jacob oth Jörg Köhl oth Marc Ehlers oth Keith Stringer oth Shiva Kumar Shanmukhappa oth David Witte oth Md Monir Hossain oth Marat Khodoun oth Andrew B Herr oth Fred D Finkelman oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 517(2015), 7535, Seite 501-504 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:517 year:2015 number:7535 pages:501-504 http://dx.doi.org/10.1038/nature13868 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25363774 http://search.proquest.com/docview/1650543912 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 517 2015 7535 501-504
spelling	10.1038/nature13868 doi PQ20160617 (DE-627)OLC1962476901 (DE-599)GBVOLC1962476901 (PRQ)c2288-c2e2a7b350510209b32cdfd82624a367579af8fb2f8c8094c092f653df777fab0 (KEY)0072945020150000517753500501igg1protectsagainstrenaldiseaseinamousemodelofcryo DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Richard T Strait verfasserin aut IgG1 protects against renal disease in a mouse model of cryoglobulinaemia 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology. Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology Monica T Posgai oth Ashley Mahler oth Nathaniel Barasa oth Chaim O Jacob oth Jörg Köhl oth Marc Ehlers oth Keith Stringer oth Shiva Kumar Shanmukhappa oth David Witte oth Md Monir Hossain oth Marat Khodoun oth Andrew B Herr oth Fred D Finkelman oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 517(2015), 7535, Seite 501-504 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:517 year:2015 number:7535 pages:501-504 http://dx.doi.org/10.1038/nature13868 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25363774 http://search.proquest.com/docview/1650543912 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 517 2015 7535 501-504
allfields_unstemmed	10.1038/nature13868 doi PQ20160617 (DE-627)OLC1962476901 (DE-599)GBVOLC1962476901 (PRQ)c2288-c2e2a7b350510209b32cdfd82624a367579af8fb2f8c8094c092f653df777fab0 (KEY)0072945020150000517753500501igg1protectsagainstrenaldiseaseinamousemodelofcryo DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Richard T Strait verfasserin aut IgG1 protects against renal disease in a mouse model of cryoglobulinaemia 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology. Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology Monica T Posgai oth Ashley Mahler oth Nathaniel Barasa oth Chaim O Jacob oth Jörg Köhl oth Marc Ehlers oth Keith Stringer oth Shiva Kumar Shanmukhappa oth David Witte oth Md Monir Hossain oth Marat Khodoun oth Andrew B Herr oth Fred D Finkelman oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 517(2015), 7535, Seite 501-504 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:517 year:2015 number:7535 pages:501-504 http://dx.doi.org/10.1038/nature13868 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25363774 http://search.proquest.com/docview/1650543912 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 517 2015 7535 501-504
allfieldsGer	10.1038/nature13868 doi PQ20160617 (DE-627)OLC1962476901 (DE-599)GBVOLC1962476901 (PRQ)c2288-c2e2a7b350510209b32cdfd82624a367579af8fb2f8c8094c092f653df777fab0 (KEY)0072945020150000517753500501igg1protectsagainstrenaldiseaseinamousemodelofcryo DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Richard T Strait verfasserin aut IgG1 protects against renal disease in a mouse model of cryoglobulinaemia 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology. Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology Monica T Posgai oth Ashley Mahler oth Nathaniel Barasa oth Chaim O Jacob oth Jörg Köhl oth Marc Ehlers oth Keith Stringer oth Shiva Kumar Shanmukhappa oth David Witte oth Md Monir Hossain oth Marat Khodoun oth Andrew B Herr oth Fred D Finkelman oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 517(2015), 7535, Seite 501-504 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:517 year:2015 number:7535 pages:501-504 http://dx.doi.org/10.1038/nature13868 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25363774 http://search.proquest.com/docview/1650543912 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 517 2015 7535 501-504
allfieldsSound	10.1038/nature13868 doi PQ20160617 (DE-627)OLC1962476901 (DE-599)GBVOLC1962476901 (PRQ)c2288-c2e2a7b350510209b32cdfd82624a367579af8fb2f8c8094c092f653df777fab0 (KEY)0072945020150000517753500501igg1protectsagainstrenaldiseaseinamousemodelofcryo DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Richard T Strait verfasserin aut IgG1 protects against renal disease in a mouse model of cryoglobulinaemia 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology. Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology Monica T Posgai oth Ashley Mahler oth Nathaniel Barasa oth Chaim O Jacob oth Jörg Köhl oth Marc Ehlers oth Keith Stringer oth Shiva Kumar Shanmukhappa oth David Witte oth Md Monir Hossain oth Marat Khodoun oth Andrew B Herr oth Fred D Finkelman oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 517(2015), 7535, Seite 501-504 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:517 year:2015 number:7535 pages:501-504 http://dx.doi.org/10.1038/nature13868 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25363774 http://search.proquest.com/docview/1650543912 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 517 2015 7535 501-504
language	English
source	Enthalten in Nature 517(2015), 7535, Seite 501-504 volume:517 year:2015 number:7535 pages:501-504
sourceStr	Enthalten in Nature 517(2015), 7535, Seite 501-504 volume:517 year:2015 number:7535 pages:501-504
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology
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container_title	Nature
authorswithroles_txt_mv	Richard T Strait @@aut@@ Monica T Posgai @@oth@@ Ashley Mahler @@oth@@ Nathaniel Barasa @@oth@@ Chaim O Jacob @@oth@@ Jörg Köhl @@oth@@ Marc Ehlers @@oth@@ Keith Stringer @@oth@@ Shiva Kumar Shanmukhappa @@oth@@ David Witte @@oth@@ Md Monir Hossain @@oth@@ Marat Khodoun @@oth@@ Andrew B Herr @@oth@@ Fred D Finkelman @@oth@@
publishDateDaySort_date	2015-01-01T00:00:00Z
hierarchy_top_id	129292834
dewey-sort	270
id	OLC1962476901
language_de	englisch
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author	Richard T Strait
spellingShingle	Richard T Strait ddc 070 ddc 500 fid BIODIV misc Kidney diseases misc Immune system misc Medical research misc Rodents misc Cryoglobulinemia - immunology misc Antigen-Antibody Complex - chemistry misc Glomerulonephritis - etiology misc Antibodies, Monoclonal - immunology misc Antigen-Antibody Complex - immunology misc Glomerulonephritis - immunology misc Cryoglobulinemia - pathology misc Immunoglobulin G - immunology misc Cryoglobulinemia - complications misc Trinitrobenzenes - immunology misc Antigens - immunology misc Glomerulonephritis - prevention & control misc Glomerulonephritis - pathology IgG1 protects against renal disease in a mouse model of cryoglobulinaemia
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topic_title	070 500 DNB 500 AVZ BIODIV fid IgG1 protects against renal disease in a mouse model of cryoglobulinaemia Kidney diseases Immune system Medical research Rodents Cryoglobulinemia - immunology Antigen-Antibody Complex - chemistry Glomerulonephritis - etiology Antibodies, Monoclonal - immunology Antigen-Antibody Complex - immunology Glomerulonephritis - immunology Cryoglobulinemia - pathology Immunoglobulin G - immunology Cryoglobulinemia - complications Trinitrobenzenes - immunology Antigens - immunology Glomerulonephritis - prevention & control Glomerulonephritis - pathology
topic	ddc 070 ddc 500 fid BIODIV misc Kidney diseases misc Immune system misc Medical research misc Rodents misc Cryoglobulinemia - immunology misc Antigen-Antibody Complex - chemistry misc Glomerulonephritis - etiology misc Antibodies, Monoclonal - immunology misc Antigen-Antibody Complex - immunology misc Glomerulonephritis - immunology misc Cryoglobulinemia - pathology misc Immunoglobulin G - immunology misc Cryoglobulinemia - complications misc Trinitrobenzenes - immunology misc Antigens - immunology misc Glomerulonephritis - prevention & control misc Glomerulonephritis - pathology
topic_unstemmed	ddc 070 ddc 500 fid BIODIV misc Kidney diseases misc Immune system misc Medical research misc Rodents misc Cryoglobulinemia - immunology misc Antigen-Antibody Complex - chemistry misc Glomerulonephritis - etiology misc Antibodies, Monoclonal - immunology misc Antigen-Antibody Complex - immunology misc Glomerulonephritis - immunology misc Cryoglobulinemia - pathology misc Immunoglobulin G - immunology misc Cryoglobulinemia - complications misc Trinitrobenzenes - immunology misc Antigens - immunology misc Glomerulonephritis - prevention & control misc Glomerulonephritis - pathology
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title	IgG1 protects against renal disease in a mouse model of cryoglobulinaemia
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title_full	IgG1 protects against renal disease in a mouse model of cryoglobulinaemia
author_sort	Richard T Strait
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title_sort	igg1 protects against renal disease in a mouse model of cryoglobulinaemia
title_auth	IgG1 protects against renal disease in a mouse model of cryoglobulinaemia
abstract	Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology.
abstractGer	Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology.
abstract_unstemmed	Immunoglobulins protect against disease to a considerable extent by activating complement and stimulatory immunoglobulin crystallizable fragment receptors (Ig FcRs), and aggregating microbial pathogens. Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology.
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title_short	IgG1 protects against renal disease in a mouse model of cryoglobulinaemia
url	http://dx.doi.org/10.1038/nature13868 http://www.ncbi.nlm.nih.gov/pubmed/25363774 http://search.proquest.com/docview/1650543912
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up_date	2024-07-04T03:40:20.458Z
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Yet IgG1, the predominant murine serum Ig isotype, cannot activate complement by the classical pathway, binds more avidly to an inhibitory than to stimulatory FcRs, and has limited ability to aggregate pathogens. In these regards, it resembles human IgG4 (ref. 4). We hypothesized that limited ability to activate effector mechanisms might protect against immune complex immunopathology. Here we show that IgG1-deficient (γ1^sup -^) mice, immunized with a potent antigen, develop lethal renal disease soon after they begin to produce antigen-specific antibody, whereas similarly immunized wild-type mice remain healthy. Surprisingly, renal disease in this model is complement and FcR independent and results from immune complex precipitation in glomerular capillaries, as in some cryoglobulinaemic humans. IgG3, which self-associates to form large immune complexes, accounts for more than 97% of the mouse Ig in this cryoglobulin; furthermore, glomerular disease develops when mice are injected with IgG3 anti-trinitrophenyl (TNP) monoclonal antibody followed by a TNP-labelled protein. Renal disease is prevented in both active and passive immunization models by antigen-specific IgG1; other isotypes are less potent at preventing disease. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms, reveal an immune-complex-dependent, complement- and FcR-independent nephrotoxic mechanism, and suggest that isotypes that poorly activate effector mechanisms may be useful for inhibiting immune complex immunopathology.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kidney diseases</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immune system</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Medical research</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rodents</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cryoglobulinemia - immunology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Antigen-Antibody Complex - chemistry</subfield></datafield><datafield tag="650" ind1=" " 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IgG1 protects against renal disease in a mouse model of cryoglobulinaemia

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