IgG Glycan Hydrolysis Attenuates ANCA-Mediated Glomerulonephritis
van Timmeren, Mirjan M. ; van der Veen, Betty S. ; Stegeman, Coen A. ; Petersen, Arjen H. ; Hellmark, Thomas ; Collin, Mattias LU
and Heeringa, Peter
(2010)
In Journal of the American Society of Nephrology
21(7).
p.1103-1114
- Abstract
- Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor mediated activation of leukocytes and complement Here, we investigated whether IgG hydrolysis by the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN. In vitro, treatment of ANCA IgG with EndoS significantly attenuated ANCA-mediated neutrophil activation without affecting antigen-binding capacity. In a mouse model of antiMPO IgG/LPS-induced NCGN, we induced disease with either unmodified or... (More)
- Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor mediated activation of leukocytes and complement Here, we investigated whether IgG hydrolysis by the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN. In vitro, treatment of ANCA IgG with EndoS significantly attenuated ANCA-mediated neutrophil activation without affecting antigen-binding capacity. In a mouse model of antiMPO IgG/LPS-induced NCGN, we induced disease with either unmodified or EndoS-treated (deglycosylated) anti-MPO IgG. In separate experiments, we administered EndoS systemically after disease induction with unmodified anti-MPO IgG. Pretreatment of anti-MPO IgG with EndoS reduced hematuria, leukocyturia, and albuminuria and attenuated both neutrophil influx and formation of glomerular crescents After inducing disease with unmodified anti-MPO IgG, systemic treatment with EndoS reduced albuminuria and glomerular crescent formation when initiated after 3 but not 24 hours. In conclusion, IgG glycan hydrolysis by EndoS attenuates ANCA-induced neutrophil activation in vitro and prevents induction of anti-MPO IgG/LPS-mediated NCGN m vivo. Systemic treatment with EndoS early after disease induction attenuates the development of disease. Thus, modulation of IgG glycosylation is a promising strategy to interfere with ANCA-mediated inflammatory processes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1654365
- author
- van Timmeren, Mirjan M.
; van der Veen, Betty S.
; Stegeman, Coen A.
; Petersen, Arjen H.
; Hellmark, Thomas
; Collin, Mattias
LU
and Heeringa, Peter
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Society of Nephrology
- volume
- 21
- issue
- 7
- pages
- 1103 - 1114
- publisher
- American Society of Nephrology
- external identifiers
-
- wos:000280447100011
- scopus:77954614475
- pmid:20448018
- ISSN
- 1046-6673
- DOI
- 10.1681/ASN.2009090984
- language
- English
- LU publication?
- yes
- id
- 3ca6cdeb-fdd1-4baa-b0f7-2b4612762cab (old id 1654365)
- alternative location
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152232/
- date added to LUP
- 2016-04-01 13:28:43
- date last changed
- 2022-03-29 07:41:51
@article{3ca6cdeb-fdd1-4baa-b0f7-2b4612762cab,
abstract = {{Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (Pr3) are considered pathogenic in ANCA-associated necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. Modulation of ANCA IgG glycosylation may potentially reduce its pathogenicity by abolishing Fc receptor mediated activation of leukocytes and complement Here, we investigated whether IgG hydrolysis by the bacterial enzyme endoglycosidase S (EndoS) attenuates ANCA-mediated NCGN. In vitro, treatment of ANCA IgG with EndoS significantly attenuated ANCA-mediated neutrophil activation without affecting antigen-binding capacity. In a mouse model of antiMPO IgG/LPS-induced NCGN, we induced disease with either unmodified or EndoS-treated (deglycosylated) anti-MPO IgG. In separate experiments, we administered EndoS systemically after disease induction with unmodified anti-MPO IgG. Pretreatment of anti-MPO IgG with EndoS reduced hematuria, leukocyturia, and albuminuria and attenuated both neutrophil influx and formation of glomerular crescents After inducing disease with unmodified anti-MPO IgG, systemic treatment with EndoS reduced albuminuria and glomerular crescent formation when initiated after 3 but not 24 hours. In conclusion, IgG glycan hydrolysis by EndoS attenuates ANCA-induced neutrophil activation in vitro and prevents induction of anti-MPO IgG/LPS-mediated NCGN m vivo. Systemic treatment with EndoS early after disease induction attenuates the development of disease. Thus, modulation of IgG glycosylation is a promising strategy to interfere with ANCA-mediated inflammatory processes.}},
author = {{van Timmeren, Mirjan M. and van der Veen, Betty S. and Stegeman, Coen A. and Petersen, Arjen H. and Hellmark, Thomas and Collin, Mattias and Heeringa, Peter}},
issn = {{1046-6673}},
language = {{eng}},
number = {{7}},
pages = {{1103--1114}},
publisher = {{American Society of Nephrology}},
series = {{Journal of the American Society of Nephrology}},
title = {{IgG Glycan Hydrolysis Attenuates ANCA-Mediated Glomerulonephritis}},
url = {{http://dx.doi.org/10.1681/ASN.2009090984}},
doi = {{10.1681/ASN.2009090984}},
volume = {{21}},
year = {{2010}},
}