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IdeS: A Bacterial Proteolytic Enzyme with Therapeutic Potential.

Johansson, Björn LU ; Shannon, Oonagh LU and Björck, Lars LU (2008) In PLoS ONE 3(2).
Abstract
BACKGROUND: IdeS, a proteinase from Streptococcus pyogenes, cleaves immunoglobulin (Ig)G antibodies with a unique degree of specificity. Pathogenic IgG antibodies constitute an important clinical problem contributing to the pathogenesis of a number of autoimmune conditions and acute transplant rejection. To be able to effectively remove such antibodies is therefore an important clinical challenge. METHODOLOGY/PRINCIPAL FINDINGS: IdeS was found to specifically and efficiently cleave IgG in human blood in vitro (20 microg of IdeS caused a complete degradation of IgG in one ml of human whole blood in 15 minutes) and to clear IgG from the blood stream of rabbits in vivo (no IgG was detected six hours following an intravenous injection of 5 mg... (More)
BACKGROUND: IdeS, a proteinase from Streptococcus pyogenes, cleaves immunoglobulin (Ig)G antibodies with a unique degree of specificity. Pathogenic IgG antibodies constitute an important clinical problem contributing to the pathogenesis of a number of autoimmune conditions and acute transplant rejection. To be able to effectively remove such antibodies is therefore an important clinical challenge. METHODOLOGY/PRINCIPAL FINDINGS: IdeS was found to specifically and efficiently cleave IgG in human blood in vitro (20 microg of IdeS caused a complete degradation of IgG in one ml of human whole blood in 15 minutes) and to clear IgG from the blood stream of rabbits in vivo (no IgG was detected six hours following an intravenous injection of 5 mg of IdeS) without any side effects. In a mouse model of immune thrombocytopenic purpura (ITP), polyclonal IgG antibodies against platelet surface antigens were used to induce a lethal disease. These profoundly thrombocytopenic animals were treated and cured by a single injection of IdeS. CONCLUSIONS/SIGNIFICANCE: Novel information is provided concerning the IgG-cleaving activity of IdeS in vitro and in vivo. The highly specific and rapid elimination of IgG in vivo, the dramatic effect in a mouse model of ITP, and the lack of side effects in the treated animals, indicate that IdeS could also be used to treat IgG-driven diseases in humans. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
3
issue
2
publisher
Public Library of Science
external identifiers
  • pmid:18301769
  • wos:000260586500036
  • scopus:44449121775
ISSN
1932-6203
DOI
10.1371/journal.pone.0001692
language
English
LU publication?
yes
id
4203ede3-7d58-461c-a32c-5690dbcbf92b (old id 1041483)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18301769?dopt=Abstract
date added to LUP
2008-03-06 11:39:30
date last changed
2017-03-05 04:22:15
@article{4203ede3-7d58-461c-a32c-5690dbcbf92b,
  abstract     = {BACKGROUND: IdeS, a proteinase from Streptococcus pyogenes, cleaves immunoglobulin (Ig)G antibodies with a unique degree of specificity. Pathogenic IgG antibodies constitute an important clinical problem contributing to the pathogenesis of a number of autoimmune conditions and acute transplant rejection. To be able to effectively remove such antibodies is therefore an important clinical challenge. METHODOLOGY/PRINCIPAL FINDINGS: IdeS was found to specifically and efficiently cleave IgG in human blood in vitro (20 microg of IdeS caused a complete degradation of IgG in one ml of human whole blood in 15 minutes) and to clear IgG from the blood stream of rabbits in vivo (no IgG was detected six hours following an intravenous injection of 5 mg of IdeS) without any side effects. In a mouse model of immune thrombocytopenic purpura (ITP), polyclonal IgG antibodies against platelet surface antigens were used to induce a lethal disease. These profoundly thrombocytopenic animals were treated and cured by a single injection of IdeS. CONCLUSIONS/SIGNIFICANCE: Novel information is provided concerning the IgG-cleaving activity of IdeS in vitro and in vivo. The highly specific and rapid elimination of IgG in vivo, the dramatic effect in a mouse model of ITP, and the lack of side effects in the treated animals, indicate that IdeS could also be used to treat IgG-driven diseases in humans.},
  articleno    = {e1692},
  author       = {Johansson, Björn and Shannon, Oonagh and Björck, Lars},
  issn         = {1932-6203},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {IdeS: A Bacterial Proteolytic Enzyme with Therapeutic Potential.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0001692},
  volume       = {3},
  year         = {2008},
}