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?

  1. Christian Lood1,†,*,
  2. Maria Allhorn2,†,‡,
  3. Rolf Lood2,
  4. Birgitta Gullstrand3,
  5. Anders I. Olin2,‡,
  6. Lars Rönnblom4,
  7. Lennart Truedsson3,§,
  8. Mattias Collin2,‡,¶,
  9. Anders A. Bengtsson1

Article first published online: 27 JUL 2012

DOI: 10.1002/art.34454

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 64, Issue 8, pages 2698–2706, August 2012

Additional Information

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

Author Information

  1. 1

    Division of Rheumatology, Skåne University Hospital and Lund University, Lund, Sweden

  2. 2

    Division of Infection Medicine, Lund University, Lund, Sweden

  3. 3

    Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden

  4. 4

    Department of Medical Sciences, Uppsala University, Uppsala, Sweden

  1. †

    Dr. C. Lood and Dr. Allhorn contributed equally to this work.

  2. ‡

    Patent applications for the in vitro and in vivo use of EndoS have been submitted by Genovis AB and Hansa Medical AB, respectively; Drs. Allhorn, Olin, and Collin are listed as inventors on these applications and have a royalty agreement with Genovis AB for products based on the in vitro use of EndoS.

  3. §

    Dr. Truedsson has received consulting fees from Shire Human Genetic Therapies (less than $10,000).

  4. Dr. Collin has received consulting fees from Hansa Medical AB (less than $10,000).

*Lund University, Department of Clinical Sciences, Division of Rheumatology, SE-221 85 Lund, Sweden

  1. †

    Dr. C. Lood and Dr. Allhorn contributed equally to this work.

  2. ‡

    Patent applications for the in vitro and in vivo use of EndoS have been submitted by Genovis AB and Hansa Medical AB, respectively; Drs. Allhorn, Olin, and Collin are listed as inventors on these applications and have a royalty agreement with Genovis AB for products based on the in vitro use of EndoS.

  3. §

    Dr. Truedsson has received consulting fees from Shire Human Genetic Therapies (less than $10,000).

  4. Dr. Collin has received consulting fees from Hansa Medical AB (less than $10,000).

Publication History

  1. Issue published online: 27 JUL 2012
  2. Article first published online: 27 JUL 2012
  3. Accepted manuscript online: 5 MAR 2012 03:42PM EST
  4. Manuscript Accepted: 21 FEB 2012
  5. Manuscript Received: 27 SEP 2011

Funded by

  • 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

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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 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.

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-α (IFNα) production by PDCs.

Results

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.

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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