In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner
Albert, Heike ; Collin, Mattias LU
; Dudziak, Diana
; Ravetch, Jeffrey V.
and Nimmerjahn, Falk
(2008)
In Proceedings of the National Academy of Sciences
105(39).
p.15005-15009
- Abstract
- IgG antibodies are potent inducers of proinflammatory responses. During autoimmune diseases such as arthritis and systemic lupus erythematosus, IgG autoantibodies are responsible for the chronic inflammation and destruction of healthy tissues by cross-linking Fc receptors on innate immune effector cells. The sugar moiety attached to the asparagine-297 residue in the constant domain of the antibody is critical for the overall structure and function of the molecule. Removal of this sugar domain leads to the loss of the proinflammatory activity, suggesting that in vivo modulation of antibody glycosylation might be a strategy to interfere with autoimmune processes. In this work, we investigated whether removal of the majority of the... (More)
- IgG antibodies are potent inducers of proinflammatory responses. During autoimmune diseases such as arthritis and systemic lupus erythematosus, IgG autoantibodies are responsible for the chronic inflammation and destruction of healthy tissues by cross-linking Fc receptors on innate immune effector cells. The sugar moiety attached to the asparagine-297 residue in the constant domain of the antibody is critical for the overall structure and function of the molecule. Removal of this sugar domain leads to the loss of the proinflammatory activity, suggesting that in vivo modulation of antibody glycosylation might be a strategy to interfere with autoimmune processes. In this work, we investigated whether removal of the majority of the IgG-associated sugar domain by endoglycosidase S (EndoS) from Streptococcus pyogenes is able to interfere with autoimmune inflammation. We demonstrate that EndoS injection efficiently removes the IgG-associated sugar domain in vivo and interferes with autoantibody-mediated proinflammatory processes in a variety of autoimmune models. Importantly, however, we observed a differential impact of EndoS-mediated sugar side chain hydrolysis on IgG activity depending on the individual IgG subclass. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1377555
- author
- Albert, Heike
; Collin, Mattias
LU
; Dudziak, Diana
; Ravetch, Jeffrey V.
and Nimmerjahn, Falk
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- immunotherapy, Fc-receptor, autoantibody, endoglycosidase
- in
- Proceedings of the National Academy of Sciences
- volume
- 105
- issue
- 39
- pages
- 15005 - 15009
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000261914300033
- scopus:54449089342
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0808248105
- language
- English
- LU publication?
- yes
- id
- e4cb1880-a3d4-4543-b5aa-f7c9ed5ac271 (old id 1377555)
- date added to LUP
- 2016-04-01 12:20:30
- date last changed
- 2022-03-28 23:35:18
@article{e4cb1880-a3d4-4543-b5aa-f7c9ed5ac271,
abstract = {{IgG antibodies are potent inducers of proinflammatory responses. During autoimmune diseases such as arthritis and systemic lupus erythematosus, IgG autoantibodies are responsible for the chronic inflammation and destruction of healthy tissues by cross-linking Fc receptors on innate immune effector cells. The sugar moiety attached to the asparagine-297 residue in the constant domain of the antibody is critical for the overall structure and function of the molecule. Removal of this sugar domain leads to the loss of the proinflammatory activity, suggesting that in vivo modulation of antibody glycosylation might be a strategy to interfere with autoimmune processes. In this work, we investigated whether removal of the majority of the IgG-associated sugar domain by endoglycosidase S (EndoS) from Streptococcus pyogenes is able to interfere with autoimmune inflammation. We demonstrate that EndoS injection efficiently removes the IgG-associated sugar domain in vivo and interferes with autoantibody-mediated proinflammatory processes in a variety of autoimmune models. Importantly, however, we observed a differential impact of EndoS-mediated sugar side chain hydrolysis on IgG activity depending on the individual IgG subclass.}},
author = {{Albert, Heike and Collin, Mattias and Dudziak, Diana and Ravetch, Jeffrey V. and Nimmerjahn, Falk}},
issn = {{1091-6490}},
keywords = {{immunotherapy; Fc-receptor; autoantibody; endoglycosidase}},
language = {{eng}},
number = {{39}},
pages = {{15005--15009}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner}},
url = {{http://dx.doi.org/10.1073/pnas.0808248105}},
doi = {{10.1073/pnas.0808248105}},
volume = {{105}},
year = {{2008}},
}