Dr. C. Lood and Dr. Allhorn contributed equally to this work.
Systemic Lupus Erythematosus
IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?
Version of Record online: 27 JUL 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 8, pages 2698–2706, August 2012
How to Cite
Lood, C., Allhorn, M., Lood, R., Gullstrand, B., Olin, A. I., Rönnblom, L., Truedsson, L., Collin, M. and Bengtsson, A. A. (2012), IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?. Arthritis & Rheumatism, 64: 2698–2706. doi: 10.1002/art.34454
- Issue online: 27 JUL 2012
- Version of Record online: 27 JUL 2012
- Accepted manuscript online: 5 MAR 2012 03:42PM EST
- Manuscript Accepted: 21 FEB 2012
- Manuscript Received: 27 SEP 2011
- Swedish Research Council. Grant Numbers: Projects 2011-52X-12672-14-3, 2005-4791, 2010-57X-20240, 2008-2201
- Medical Faculty at Lund University
- Alfred Österlund Foundation
- The 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 and Ragnar Söderberg Foundations
- Royal Physiografic Society
- Åke Wiberg Foundation
- Swedish COMBINE projects
- Hansa Medical AB
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 Fcγ receptors (FcγR) with subsequent inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycan–hydrolyzing 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.
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-α (IFNα) production by PDCs.
EndoS treatment abolished all proinflammatory properties of the ICs investigated. This included FcγR-mediated phagocytosis by PDCs (P = 0.001) and subsequent production of IFNα (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.
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.