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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)
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author
organization
publishing date
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 Acad 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
2009-04-24 10:35:13
date last changed
2017-08-06 03:46:08
@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},
  keyword      = {immunotherapy,Fc-receptor,autoantibody,endoglycosidase},
  language     = {eng},
  number       = {39},
  pages        = {15005--15009},
  publisher    = {National Acad 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},
  volume       = {105},
  year         = {2008},
}