Streptococcal Endo-β- N-Acetylglucosaminidase Suppresses Antibody-Mediated Inflammation In Vivo

  • Front Immunol. 2018 Jul 16;9:1623. doi: 10.3389/fimmu.2018.01623.
Kutty Selva Nandakumar  1  2 ,  Mattias Collin  3 ,  Kaisa E Happonen  4  5 ,  Susanna L Lundström  6 ,  Allyson M Croxford  7 ,  Bingze Xu  2 ,  Roman A Zubarev  6 ,  Merrill J Rowley  7 ,  Anna M Blom  4 ,  Christian Kjellman  8 ,  Rikard Holmdahl  1  2
Affiliations
  • 1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
  • 2. Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  • 3. Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • 4. Department of Translational Medicine, Lund University, Lund, Sweden.
  • 5. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States.
  • 6. Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  • 7. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
  • 8. Hansa Medical AB, Lund, Sweden.
PMID: 30061892 DOI: 10.3389/fimmu.2018.01623
Abstract

Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes. Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG. Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated Arthritis. A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated Arthritis in mice. The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining. Neither complement binding in vitro nor antigen-antibody binding per se were affected. Thus, EndoS could potentially be used for treating patients with IC-mediated pathology.

Keywords
arthritis; complement; endoglycosidase; glycosylation; immunoglobulin G; immunohistochemistry; mouse models; rheumatoid.
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