title: Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis.
abstract: OBJECTIVE
  To identify a cartilage-derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process.
  
  
  METHODS
  A DR4 (DRB1*0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein-39 (HC gp-39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RA-associated DR4 (DRB1*0401) molecules. High-affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp-39, the protein was injected into BALB/c mice.
  
  
  RESULTS
  HC gp-39-derived motif-based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen-specific T cells and to suppression of HC gp-39-induced arthritis.
  
  
  CONCLUSIONS
  These data indicate that HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a candidate for antigen-specific immunotherapy.
authors.affiliation: NV Organon, Oss, The Netherlands.
authors.forename: G F
authors.initials: GF
authors.lastname: Verheijden
authors.forename: A W
authors.initials: AW
authors.lastname: Rijnders
authors.forename: E
authors.initials: E
authors.lastname: Bos
authors.forename: C J
authors.initials: CJ
authors.lastname: Coenen-de Roo
authors.forename: C J
authors.initials: CJ
authors.lastname: van Staveren
authors.forename: A M
authors.initials: AM
authors.lastname: Miltenburg
authors.forename: J H
authors.initials: JH
authors.lastname: Meijerink
authors.forename: D
authors.initials: D
authors.lastname: Elewaut
authors.forename: F
authors.initials: F
authors.lastname: de Keyser
authors.forename: E
authors.initials: E
authors.lastname: Veys
authors.forename: A M
authors.initials: AM
authors.lastname: Boots
mesh_terms: D054392:Adipokines; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002356:Cartilage / Q000276:immunology; D000071451:Chitinase-3-Like Protein 1; D002999:Clone Cells; D000939:Epitopes; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D037102:Lectins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D054392:Adipokines; D001324:Autoantigens; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D000939:Epitopes; D006023:Glycoproteins; D037102:Lectins; D010455:Peptides