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Blocking of experimental arthritis by cleavage of IgG antibodies in vivo

På svenska

Author

  • Kutty Selva Nandakumar
  • Björn Johansson
  • Lars Björck
  • Rikard Holmdahl

Summary, in English

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.

Department/s

Publishing year

2007

Language

English

Pages

3253-3260

Publication/Series

Arthritis and Rheumatism

Volume

56

Issue

10

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Rheumatology and Autoimmunity

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1529-0131