title: Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis.
abstract: BACKGROUND
  Unravelling the basis of joint inflammation and ankylosis represents a major challenge in ankylosing spondylitis (AS) research. As noggin (NOG) and sclerostin (SOST) have recently been associated with the disease process in mouse and human studies, respectively, we explored the immune responses to these two molecules in AS.
  
  
  METHODS
  Immune complexes (IC) composed of IgG autoantibodies to NOG and SOST were detected by immunoprecipitation and Western blot analyses. Epitope-specific IgG were measured using peptide-binding ELISA. Serum samples were obtained from healthy controls and patients with AS, mechanical back pain (MBP) and inflammatory bowel disease (IBD) with or without concomitant AS.
  
  
  RESULTS
  NOG and SOST-IgG IC were present in NOG-treated and untreated ank/ank (progressive ankylosis), but not in wild-type mice. Higher than normal levels of NOG and SOST-IgG IC are present in AS sera (p<0.001). We showed a SOST peptide (SOST-S146, with homology to a bacterial glycotransferase peptide) binds to a NOG peptide (NOG-N54), which contains a N-glycosylation site. AS patients have higher levels of IgG recognising the NOG-N54 and SOST-S146 peptides compared to the levels in normal controls, IBD and MBP patients (one way analysis of variance p<0.0001).
  
  
  CONCLUSIONS
  This is the first report showing IgG autoantibodies to NOG and SOST in normal individuals, and higher levels of NOG and/or SOST-IgG IC probably contribute to neo-ossification in AS patients. These novel findings hold the promise of earlier diagnosis, better management of AS with comorbidities and new therapeutic approaches to modulate ankylosis in AS.
authors.affiliation: Genetics and Development Division, TorontoWestern Research Institute, University Health Network, Toronto, Ontario, Canada Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Florence W L
authors.initials: FW
authors.lastname: Tsui
authors.affiliation: Genetics and Development Division, TorontoWestern Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Hing Wo
authors.initials: HW
authors.lastname: Tsui
authors.affiliation: Department of Anatomical Pathology, University of Chile Clinical Hospital, Santiago, Chile.
authors.forename: Facundo
authors.initials: F
authors.lastname: Las Heras
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Kenneth P H
authors.initials: KP
authors.lastname: Pritzker
authors.affiliation: Genetics and Development Division, TorontoWestern Research Institute, University Health Network, Toronto, Ontario, Canada Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood / Q000276:immunology*; D002352:Carrier Proteins / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D005819:Genetic Markers / Q000276:immunology*; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000276:immunology*; D000099176:Noggin Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D000099176:Noggin Protein; C422903:SOST protein, human; C486030:Sost protein, mouse
keywords: Ankylosing Spondylitis; Autoantibodies; Autoimmunity