Blocking of experimental arthritis by cleavage of IgG antibodies in vivo
(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:
https://lup.lub.lu.se/record/654406
- author
- Nandakumar, Kutty Selva ; Johansson, Björn LU ; Björck, Lars LU and Holmdahl, Rikard LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 56
- issue
- 10
- pages
- 3253 - 3260
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000250264800012
- scopus:35348848012
- pmid:17907170
- ISSN
- 1529-0131
- DOI
- 10.1002/art.22930
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Infection Medicine (BMC) (013024020), Medical Inflammation Research (013212019)
- 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
- 2016-04-01 11:46:38
- date last changed
- 2022-03-13 00:34:04
@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 Inc.}}, 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}}, doi = {{10.1002/art.22930}}, volume = {{56}}, year = {{2007}}, }