Clinical immunology

Endoglycosidase treatment abrogates IgG arthritogenicity: Importance of IgG glycosylation in arthritis

  1. Kutty Selva Nandakumar Dr.1,*,
  2. Mattias Collin2,
  3. Arne Olsén2,
  4. Falk Nimmerjahn3,5,
  5. Anna M. Blom4,
  6. Jeffrey V. Ravetch3,
  7. Rikard Holmdahl1

Article first published online: 26 SEP 2007

DOI: 10.1002/eji.200737581

Issue

European Journal of Immunology

European Journal of Immunology

Volume 37, Issue 10, pages 2973–2982, October 2007

Additional Information

How to Cite

Nandakumar, K., Collin, M., Olsén, A., Nimmerjahn, F., Blom, Anna M., Ravetch, Jeffrey V. and Holmdahl, R. (2007), Endoglycosidase treatment abrogates IgG arthritogenicity: Importance of IgG glycosylation in arthritis. Eur. J. Immunol., 37: 2973–2982. doi: 10.1002/eji.200737581

Author Information

  1. 1

    Medical Inflammation Research, Lund University, Lund, Sweden

  2. 2

    Division of Infection Medicine, Lund University, Lund, Sweden

  3. 3

    Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, USA

  4. 4

    Department of Laboratory Medicine, Lund University, Lund, Sweden

  5. 5

    Experimental Immunology and Immunotherapy, Nikolaus Fiebiger Center for Molecular Medicine, University of Erlangen-Nuremberg, Erlangen-Nuremberg, Germany

*Medical Inflammation Research, Lund University, BMC, I11, SE-22184 Lund, Sweden, Fax: +46-46-2223110

Publication History

  1. Issue published online: 26 SEP 2007
  2. Article first published online: 26 SEP 2007
  3. Manuscript Accepted: 13 AUG 2007
  4. Manuscript Revised: 11 JUL 2007
  5. Manuscript Received: 18 JUN 2007

Funded by

  • King Gustaf V's 80 years foundation
  • Professor Nanna Svartz foundation
  • Swedish Rheumatism Association
  • Swedish Research Council (project 2005–4791)
  • Swedish Foundation for Strategic Research
  • EU (MUGEN LSHG-CT-2005–005203; project LSHB-CT-2006–018661 (AUTOCURE
  • foundations of Crafoord, Jeansson, Zoéga, Bergvall, Österlund, Groschinsky
  • Swedish Society for Medical Research
  • Swedish Society of Medicine
  • Royal Physiografic Society
  • Medical Faculty at Lund University
  • Conflict of interest: Hansa Medical AB has filed patent applications on EndoS and A.O., M.C., R.H., and K.S.N. are listed as inventors, and the applications are pending.

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Keywords:

  • Arthritis;
  • EndoS;
  • IgG

Abstract

The glycosylation status of IgG has been implicated in the pathology of rheumatoid arthritis. Earlier, we reported the identification of a novel secreted endo-β-N-acetylglucosaminidase (EndoS), secreted by Streptococcus pyogenes that specifically hydrolyzes the β-1,4-di-N-acetylchitobiose core of the asparagine-linked glycan of human IgG. Here, we analyzed the arthritogenicity of EndoS-treated collagen type II (CII)-specific mouse mAb in vivo. Endoglycosidase treatment of the antibodies inhibited the induction of arthritis in (BALB/c × B10.Q) F1 mice and induced a milder arthritis in B10.RIII mice as compared with the severe arthritis induced by non-treated antibodies. Furthermore, EndoS treatment did not affect the binding of IgG to CII and their ability to activate complement, but it resulted in reduced IgG binding to FcγR and disturbed the formation of stable immune complexes. Hence, the asparagine-linked glycan on IgG plays a crucial role in the development of arthritis.

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