IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE - a possible new treatment?
Author
Summary, in English
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.
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.
Department/s
Publishing year
2012
Language
English
Publication/Series
Arthritis and Rheumatism
Volume
71
Issue
Suppl 1
Links
Document type
Conference paper: abstract
Publisher
John Wiley & Sons Inc.
Topic
- Rheumatology and Autoimmunity
Conference name
32nd European Workshop for Rheumatology Research
Conference date
2012-02-23 - 2012-02-25
Conference place
Stockholm, Sweden
Status
Published
Research group
- Infection and immunomodulation
ISBN/ISSN/Other
- ISSN: 1529-0131