title: Proteomic surveillance of autoimmunity in osteoarthritis: identification of triosephosphate isomerase as an autoantigen in patients with osteoarthritis.
abstract: OBJECTIVE
  Autoimmunity to proteins, such as type II collagen and cartilage intermediate layer protein, that are produced by chondrocytes has been reported in patients with osteoarthritis (OA) as well as in patients with rheumatoid arthritis (RA). However, it remains to be determined whether the overall specificities of the autoimmunity differ between OA and RA patients. This study sought to clarify the differences by applying proteomic surveillance for the detection of autoantigens comprehensively.
  
  
  METHODS
  Serum samples were obtained from 20 patients with OA, 20 patients with RA, and 20 healthy volunteers. Human chondrocyte proteins were separated from the sera by 2-dimensional electrophoresis, and antigenic protein spots were detected by Western blotting. The antigenic proteins were then identified by mass fingerprinting. The antigenicity of the identified proteins was confirmed and the prevalence of the autoantibodies in the OA, RA, and other disease groups was determined with the use of recombinant proteins. In addition, autoepitopes were mapped on the antigens.
  
  
  RESULTS
  Nineteen protein spots were recognized only by the OA sera, but not by the RA sera. One of these proteins was identified as triosephosphate isomerase (TPI). IgG-type anti-TPI autoantibodies were detected in 24.7% of the serum samples and 24.1% of the synovial fluid samples from the patients with OA, whereas <6% of the RA and systemic lupus erythematosus samples were positive for anti-TPI. In addition, multiple autoepitopes were identified on TPI.
  
  
  CONCLUSIONS
  The overall profile of autoimmunity in OA differs from that in RA, which may reflect the OA-specific pathologic role of autoimmunity. The autoantibody to TPI, detected predominantly in the OA samples and produced by the antigen-driven mechanism, has the potential to be used as a diagnostic marker for OA.
authors.affiliation: Division of Immunoregulation, Department of Bioregulation, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8512, Japan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Taichi
authors.initials: T
authors.lastname: Sekine
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukuda
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000453:epidemiology / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D015153:Blotting, Western; D019902:Chondrocytes / Q000201:enzymology / Q000276:immunology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000453:epidemiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology / Q000453:epidemiology / Q000276:immunology*; D010449:Peptide Mapping; D040901:Proteomics; D011994:Recombinant Proteins / Q000235:genetics; D016036:Seroepidemiologic Studies; D014305:Triose-Phosphate Isomerase / Q000097:blood / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D011994:Recombinant Proteins; D014305:Triose-Phosphate Isomerase