title: Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis.
abstract: OBJECTIVE
  The interferon-inducible protein 16 (IFI16) has been detected in sera from patients with autoimmune/inflammatory diseases, but not in healthy subjects. This leaking leads to loss of tolerance toward this self-protein and the development of autoantibodies. In this study, clinical significance of both IFI16 protein and anti-IFI16 antibodies in rheumatoid arthritis (RA) was investigated.
  
  
  METHODS
  IFI16 protein and anti-IFI16 antibody levels were assessed by enzyme-linked immunosorbent assay in serum samples from 154 RA patients and 182 healthy controls, and in synovial fluid (SF) samples from 21 RA patients and 25 patients with osteoarthritis (OA).
  
  
  RESULTS
  Mean serum levels for both IFI16 and anti-IFI16 antibodies were higher in RA patients than in healthy controls, with a direct correlation between IFI16 concentration and anti-IFI16 antibody titer. The majority of RA patients with detectable circulating IFI16 protein were also positive for rheumatoid factor (RF)/anti-cyclic citrullinated peptide antibody (anti-CCP). The latter group was found to be positive for anti-IFI16 antibodies as well. The mean SF concentrations of both IFI16 protein and anti-IFI16 antibodies were higher in RA patients when compared with control OA patients. Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16 antibodies, significantly correlated with RA-associated pulmonary disease. This correlation was not dependent on the presence of anti-IFI16 antibodies, sex, and smoking habit.
  
  
  CONCLUSIONS
  Our data demonstrate that the high levels of circulating IFI16 in RA are more frequent in RF/anti-CCP-positive RA patients and significantly associated with pulmonary involvement. The relevance of circulating IFI16 protein as a new clinical biomarker of RA should be verified with additional studies.
authors: University of Perugia, Perugia, Italy.
authors: Alessia
authors: A
authors: Alunno
authors: Novara Medical School, Novara, Italy.
authors: Valeria
authors: V
authors: Caneparo
authors: University of Perugia, Perugia, Italy.
authors: Onelia
authors: O
authors: Bistoni
authors: University of Perugia, Perugia, Italy.
authors: Sara
authors: S
authors: Caterbi
authors: University of Perugia, Perugia, Italy.
authors: Riccardo
authors: R
authors: Terenzi
authors: Novara Medical School, Novara, Italy.
authors: Marisa
authors: M
authors: Gariglio
authors: University of Perugia, Perugia, Italy.
authors: Elena
authors: E
authors: Bartoloni
authors: IRCCS Policlinico S. Matteo Foundation/University of Pavia, Pavia, Italy.
authors: Antonio
authors: A
authors: Manzo
authors: Turin Medical School, Turin, Italy.
authors: Santo
authors: S
authors: Landolfo
authors: University of Perugia, Perugia, Italy.
authors: Roberto
authors: R
authors: Gerli
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000097:blood* / Q000276:immunology; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology; D010750:Phosphoproteins / Q000097:blood* / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D012698:Serologic Tests; D013582:Synovial Fluid / Q000276:immunology; D015854:Up-Regulation
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D009687:Nuclear Proteins; D010456:Peptides, Cyclic; D010750:Phosphoproteins; C487763:cyclic citrullinated peptide; C076700:IFI16 protein, human; D012217:Rheumatoid Factor