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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1052625
- author
- Collin, Mattias
LU
; Shannon, Oonagh
LU
and Björck, Lars
LU
- organization
- publishing date
- 2008
- 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 Academy of Sciences
- external identifiers
-
- pmid:18332429
- wos:000254263300036
- scopus:41949141128
- pmid:18332429
- 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
- 2016-04-04 08:56:11
- date last changed
- 2022-03-31 00:43:06
@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 Academy of 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}},
doi = {{10.1073/pnas.0711271105}},
volume = {{105}},
year = {{2008}},
}