Journal
ARTHRITIS AND RHEUMATISM
Volume 64, Issue 8, Pages 2698-2706Publisher
WILEY
DOI: 10.1002/art.34454
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Funding
- Swedish Research Council [2011-52X-12672-14-3, 2005-4791, 2010-57X-20240, 2008-2201]
- Medical Faculty at Lund University
- Alfred Osterlund Foundation
- Crafoord Foundation
- Greta and Johan Kock Foundation
- King Gustaf V's 80-Year Foundation
- Lund University Hospital
- Magnus Bergvall Foundation
- Hedberg Foundation
- Swedish Rheumatism Association
- Swedish Society of Medicine
- Foundation of the National Board of Health and Welfare
- Torsten Foundation
- Ragnar Soderberg Foundation
- Royal Physiografic Society
- Ake Wiberg Foundation
- Swedish COMBINE projects
- Hansa Medical AB
- Shire Human Genetic Therapies
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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.
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