IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE - a possible new treatment?
Lood, Christian LU ; Allhorn, Maria LU ; Lood, Rolf LU ; Gullstrand, Birgitta LU ; Olin, Anders LU ; Rönnblom, Lars ; Truedsson, Lennart LU ; Collin, Mattias LU
and Bengtsson, Anders
LU
(2012)
32nd European Workshop for Rheumatology Research
In Arthritis and Rheumatism
71(Suppl 1).
- 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) which stimulate leukocytes through FcγRs with subsequent inflammation. Treatment with EndoS, an IgG glycan hydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. In the present study we asked if EndoS could affect pro-inflammatory properties of ICs and have the potential to be developed as a therapy in SLE.
METHODS.: ICs, purified from SLE patients or RNA-containing ICs formed in vitro, were treated with... (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) which stimulate leukocytes through FcγRs with subsequent inflammation. Treatment with EndoS, an IgG glycan hydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. In the present study we asked if EndoS could affect pro-inflammatory properties of ICs and have the potential to be developed as a therapy in 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 parts of SLE pathogenesis such as phagocytosis by polymorphonuclear neutrophils (PMNs) and plasmacytoid dendritic cells (pDCs), complement activation and IFNα production by pDCs.
RESULTS.: Our results demonstrate that EndoS treatment could abolish all pro-inflammatory properties of ICs investigated. This includes FcγR-mediated phagocytosis by pDCs (p<0.0001) and subsequent production of IFNα (p<0.0001), IC-induced classical complement pathway activation (p<0.0001), chemotaxis and oxidative burst activity of PMNs (p=0.002). We could also demonstrate direct effects on the molecular structure of ICs after EndoS treatment with decreased size and glycosylation patterns.
CONCLUSIONS.: Prominent effects of EndoS treatment were seen in several pathogenetically important IC-mediated events and our data suggest that EndoS have the potential to be developed as a novel therapy in SLE. © 2012 American College of Rheumatology. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2432217
- author
- Lood, Christian
LU
; Allhorn, Maria
LU
; Lood, Rolf
LU
; Gullstrand, Birgitta
LU
; Olin, Anders
LU
; Rönnblom, 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
- 71
- issue
- Suppl 1
- publisher
- John Wiley & Sons Inc.
- conference name
- 32nd European Workshop for Rheumatology Research
- conference location
- Stockholm, Sweden
- conference dates
- 2012-02-23 - 2012-02-25
- external identifiers
-
- wos:000302323600003
- pmid:22392566
- ISSN
- 1529-0131
- DOI
- 10.1136/annrheumdis-2011-201230.2
- language
- English
- LU publication?
- yes
- id
- b4d7c9cf-66ac-4c6b-b11d-d7a9da4915df (old id 2432217)
- date added to LUP
- 2016-04-04 08:07:01
- date last changed
- 2023-01-30 13:50:45
@misc{b4d7c9cf-66ac-4c6b-b11d-d7a9da4915df,
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) which stimulate leukocytes through FcγRs with subsequent inflammation. Treatment with EndoS, an IgG glycan hydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. In the present study we asked if EndoS could affect pro-inflammatory properties of ICs and have the potential to be developed as a therapy in SLE. <br/><br>
<br/><br>
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 parts of SLE pathogenesis such as phagocytosis by polymorphonuclear neutrophils (PMNs) and plasmacytoid dendritic cells (pDCs), complement activation and IFNα production by pDCs. <br/><br>
<br/><br>
RESULTS.: Our results demonstrate that EndoS treatment could abolish all pro-inflammatory properties of ICs investigated. This includes FcγR-mediated phagocytosis by pDCs (p<0.0001) and subsequent production of IFNα (p<0.0001), IC-induced classical complement pathway activation (p<0.0001), chemotaxis and oxidative burst activity of PMNs (p=0.002). We could also demonstrate direct effects on the molecular structure of ICs after EndoS treatment with decreased size and glycosylation patterns. <br/><br>
<br/><br>
CONCLUSIONS.: Prominent effects of EndoS treatment were seen in several pathogenetically important IC-mediated events and our data suggest that EndoS have the potential to be developed as a novel therapy in SLE. © 2012 American College of Rheumatology.}},
author = {{Lood, Christian and Allhorn, Maria and Lood, Rolf and Gullstrand, Birgitta and Olin, Anders and Rönnblom, Lars and Truedsson, Lennart and Collin, Mattias and Bengtsson, Anders}},
issn = {{1529-0131}},
language = {{eng}},
note = {{Conference Abstract}},
number = {{Suppl 1}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Arthritis and Rheumatism}},
title = {{IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE - a possible new treatment?}},
url = {{http://dx.doi.org/10.1136/annrheumdis-2011-201230.2}},
doi = {{10.1136/annrheumdis-2011-201230.2}},
volume = {{71}},
year = {{2012}},
}