title: IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: a possible new treatment?
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, Skåne University Hospital and Lund University, Lund, Sweden. Christian.lood@med.lu.se
authors.forename: Christian
authors.initials: C
authors.lastname: Lood
authors.forename: Maria
authors.initials: M
authors.lastname: Allhorn
authors.forename: Rolf
authors.initials: R
authors.lastname: Lood
authors.forename: Birgitta
authors.initials: B
authors.lastname: Gullstrand
authors.forename: Anders I
authors.initials: AI
authors.lastname: Olin
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000936:Antigen-Antibody Complex / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000494:pharmacology*; D002633:Chemotaxis / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D006026:Glycoside Hydrolases / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007074:Immunoglobulin G / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016898:Interferon-alpha / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D011134:Polysaccharides / Q000378:metabolism*; D017452:Receptors, IgG / Q000502:physiology; D055815:Young Adult
chemical_list: D000936:Antigen-Antibody Complex; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D016898:Interferon-alpha; D011134:Polysaccharides; D017452:Receptors, IgG; D006026:Glycoside Hydrolases; C431325:NDOS protein, Streptococcus pyogenes