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IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions.

Collin, Mattias LU ; Shannon, Oonagh LU and Björck, Lars LU (2008) In Proceedings of the National Academy of Sciences 105(11). p.4265-4270
Abstract
EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS indeed has a protective effect in a mouse model of lethal IgG-driven immune (or idiopathic)... (More)
EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS indeed has a protective effect in a mouse model of lethal IgG-driven immune (or idiopathic) thrombocytopenic purpura. EndoS pretreatment of pathogenic antibodies inhibits the development of disease, and the enzyme also rescues mice from already established disease when severe thrombocytopenia and s.c. bleeding have developed. These results identify EndoS as a potential therapeutic agent against diseases where pathogenic IgG antibodies are important and further emphasize antibody glycans as possible targets in future therapies against antibody-mediated autoimmune conditions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
105
issue
11
pages
4265 - 4270
publisher
National Acad Sciences
external identifiers
  • pmid:18332429
  • wos:000254263300036
  • scopus:41949141128
ISSN
1091-6490
DOI
10.1073/pnas.0711271105
language
English
LU publication?
yes
id
57629385-5410-4e45-b7ae-ce2ba8b71ea7 (old id 1052625)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18332429?dopt=Abstract
date added to LUP
2008-04-01 10:40:26
date last changed
2017-08-06 04:48:19
@article{57629385-5410-4e45-b7ae-ce2ba8b71ea7,
  abstract     = {EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS indeed has a protective effect in a mouse model of lethal IgG-driven immune (or idiopathic) thrombocytopenic purpura. EndoS pretreatment of pathogenic antibodies inhibits the development of disease, and the enzyme also rescues mice from already established disease when severe thrombocytopenia and s.c. bleeding have developed. These results identify EndoS as a potential therapeutic agent against diseases where pathogenic IgG antibodies are important and further emphasize antibody glycans as possible targets in future therapies against antibody-mediated autoimmune conditions.},
  author       = {Collin, Mattias and Shannon, Oonagh and Björck, Lars},
  issn         = {1091-6490},
  language     = {eng},
  number       = {11},
  pages        = {4265--4270},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions.},
  url          = {http://dx.doi.org/10.1073/pnas.0711271105},
  volume       = {105},
  year         = {2008},
}