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IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?

Lood, Christian LU ; Allhorn, Maria LU ; Lood, Rolf LU ; Gullstrand, Birgitta LU ; Olin, Anders LU ; Ronnblom, Lars; Truedsson, Lennart LU ; Collin, Mattias LU and Bengtsson, Anders LU (2012) In Arthritis and Rheumatism 64(8). p.2698-2706
Abstract
Objective Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) that stimulate leukocytes through Fc? receptors (Fc?R) with subsequent inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycanhydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. This study was undertaken to investigate whether EndoS affects the proinflammatory properties of ICs and has the potential to be developed as a therapy for SLE. Methods ICs purified from SLE patients or RNA-containing ICs formed in... (More)
Objective Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) that stimulate leukocytes through Fc? receptors (Fc?R) with subsequent inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycanhydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. This study was undertaken to investigate whether EndoS affects the proinflammatory properties of ICs and has the potential to be developed as a therapy for SLE. Methods ICs purified from SLE patients or RNA-containing ICs formed in vitro were treated with EndoS and used in several assays reflecting different important features of SLE pathogenesis, such as phagocytosis by polymorphonuclear cells (PMNs) and plasmacytoid dendritic cells (PDCs), complement activation, and interferon-a (IFNa) production by PDCs. Results EndoS treatment abolished all proinflammatory properties of the ICs investigated. This included Fc?R-mediated phagocytosis by PDCs (P = 0.001) and subsequent production of IFNa (P = 0.002), IC-induced classical pathway of complement activation (P = 0.008), chemotaxis, and oxidative burst activity of PMNs (P = 0.002). EndoS treatment also had a direct effect on the molecular structure of ICs, causing decreased IC size and glycosylation. Conclusion Our findings indicate that EndoS treatment has prominent effects on several pathogenetically important IC-mediated events, and suggest that EndoS has the potential to be developed as a novel therapy for SLE. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis and Rheumatism
volume
64
issue
8
pages
2698 - 2706
publisher
John Wiley & Sons
external identifiers
  • wos:000306906500030
  • scopus:84864484027
ISSN
1529-0131
DOI
10.1002/art.34454
language
English
LU publication?
yes
id
558fa2ed-3ee7-4d75-ba22-c85bd9b06c8f (old id 3070224)
date added to LUP
2012-10-05 07:12:33
date last changed
2017-08-06 03:12:07
@article{558fa2ed-3ee7-4d75-ba22-c85bd9b06c8f,
  abstract     = {Objective Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) that stimulate leukocytes through Fc? receptors (Fc?R) with subsequent inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycanhydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. This study was undertaken to investigate whether EndoS affects the proinflammatory properties of ICs and has the potential to be developed as a therapy for SLE. Methods ICs purified from SLE patients or RNA-containing ICs formed in vitro were treated with EndoS and used in several assays reflecting different important features of SLE pathogenesis, such as phagocytosis by polymorphonuclear cells (PMNs) and plasmacytoid dendritic cells (PDCs), complement activation, and interferon-a (IFNa) production by PDCs. Results EndoS treatment abolished all proinflammatory properties of the ICs investigated. This included Fc?R-mediated phagocytosis by PDCs (P = 0.001) and subsequent production of IFNa (P = 0.002), IC-induced classical pathway of complement activation (P = 0.008), chemotaxis, and oxidative burst activity of PMNs (P = 0.002). EndoS treatment also had a direct effect on the molecular structure of ICs, causing decreased IC size and glycosylation. Conclusion Our findings indicate that EndoS treatment has prominent effects on several pathogenetically important IC-mediated events, and suggest that EndoS has the potential to be developed as a novel therapy for SLE.},
  author       = {Lood, Christian and Allhorn, Maria and Lood, Rolf and Gullstrand, Birgitta and Olin, Anders and Ronnblom, Lars and Truedsson, Lennart and Collin, Mattias and Bengtsson, Anders},
  issn         = {1529-0131},
  language     = {eng},
  number       = {8},
  pages        = {2698--2706},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?},
  url          = {http://dx.doi.org/10.1002/art.34454},
  volume       = {64},
  year         = {2012},
}