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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3070224
- author
- 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
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 64
- issue
- 8
- pages
- 2698 - 2706
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000306906500030
- scopus:84864484027
- pmid:22392566
- 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
- 2016-04-01 10:23:28
- date last changed
- 2022-03-12 05:23:21
@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 Inc.}},
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}},
doi = {{10.1002/art.34454}},
volume = {{64}},
year = {{2012}},
}