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Blocking of experimental arthritis by cleavage of IgG antibodies in vivo

Nandakumar, Kutty Selva; Johansson, Björn LU ; Björck, Lars LU and Holmdahl, Rikard LU (2007) In Arthritis and Rheumatism 56(10). p.3253-3260
Abstract
Objective. To investigate whether IgG-degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis. Methods. Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibody-induced arthritis (CAIA), collagen-induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed. Results. IdeS efficiently cleaved mouse IgG2a/c and IgG3 in vitro. Even at low dosage (10 mu g), IdeS specifically cleaved IgG2a in vivo without any apparent side effects. IdeS treatment efficiently blocked CAIA induced by IgG2a... (More)
Objective. To investigate whether IgG-degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis. Methods. Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibody-induced arthritis (CAIA), collagen-induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed. Results. IdeS efficiently cleaved mouse IgG2a/c and IgG3 in vitro. Even at low dosage (10 mu g), IdeS specifically cleaved IgG2a in vivo without any apparent side effects. IdeS treatment efficiently blocked CAIA induced by IgG2a antibodies. No effect was observed when arthritis was induced with IgG2b anti-type 11 collagen antibodies; since IdeS does not cleave IgG2b, this indicated that IgG cleavage was the mechanism of action. IdeS treatment reduced the severity of arthritis if administered within 24 hours after the onset of clinical arthritis, but did not block ongoing severe arthritis. IdeS treatment also significantly prevented an antibody-induced relapse in mice that had chronic arthritis, and delayed the onset and reduced the severity of arthritis in classic CIA. Conclusion. IdeS has therapeutic potential in IgG antibody-mediated autoimmune arthritis, representing a new and unique means of blocking pathogenic antibodies. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis and Rheumatism
volume
56
issue
10
pages
3253 - 3260
publisher
John Wiley & Sons
external identifiers
  • wos:000250264800012
  • scopus:35348848012
ISSN
1529-0131
DOI
10.1002/art.22930
language
English
LU publication?
yes
id
d644463b-ee99-469b-a1b6-bb243132e7a8 (old id 654406)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17907170&dopt=Abstract
date added to LUP
2007-12-17 10:21:46
date last changed
2017-10-01 03:39:37
@article{d644463b-ee99-469b-a1b6-bb243132e7a8,
  abstract     = {Objective. To investigate whether IgG-degrading enzyme of Streptococcus pyogenes (IdeS), a bacterial cysteine endopeptidase that cleaves human IgG in the hinge region, can be used for blocking the development of arthritis. Methods. Recombinant IdeS was purified and tested for specificity against mouse IgG. IdeS was injected intravenously into mice with collagen antibody-induced arthritis (CAIA), collagen-induced arthritis (CIA), or relapsing CIA, and its effects on arthritis development and severity were assessed. Results. IdeS efficiently cleaved mouse IgG2a/c and IgG3 in vitro. Even at low dosage (10 mu g), IdeS specifically cleaved IgG2a in vivo without any apparent side effects. IdeS treatment efficiently blocked CAIA induced by IgG2a antibodies. No effect was observed when arthritis was induced with IgG2b anti-type 11 collagen antibodies; since IdeS does not cleave IgG2b, this indicated that IgG cleavage was the mechanism of action. IdeS treatment reduced the severity of arthritis if administered within 24 hours after the onset of clinical arthritis, but did not block ongoing severe arthritis. IdeS treatment also significantly prevented an antibody-induced relapse in mice that had chronic arthritis, and delayed the onset and reduced the severity of arthritis in classic CIA. Conclusion. IdeS has therapeutic potential in IgG antibody-mediated autoimmune arthritis, representing a new and unique means of blocking pathogenic antibodies.},
  author       = {Nandakumar, Kutty Selva and Johansson, Björn and Björck, Lars and Holmdahl, Rikard},
  issn         = {1529-0131},
  language     = {eng},
  number       = {10},
  pages        = {3253--3260},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {Blocking of experimental arthritis by cleavage of IgG antibodies in vivo},
  url          = {http://dx.doi.org/10.1002/art.22930},
  volume       = {56},
  year         = {2007},
}