title: The type I IFN signature as a biomarker of preclinical rheumatoid arthritis.
abstract: OBJECTIVE
  To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development.
  
  
  METHODS
  In 115 seropositive arthralgia patients who were followed for the development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis.
  
  
  RESULTS
  In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5-13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN(high) individuals converted to arthritis, compared with 29 out of 90 IFN(low) individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN(high) at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87).
  
  
  CONCLUSIONS
  The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.
authors: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Joyce
authors: J
authors: Lübbers
authors: Mikael
authors: M
authors: Brink
authors: Lotte A
authors: LA
authors: van de Stadt
authors: Saskia
authors: S
authors: Vosslamber
authors: John G
authors: JG
authors: Wesseling
authors: Dirkjan
authors: D
authors: van Schaardenburg
authors: Solbritt
authors: S
authors: Rantapää-Dahlqvist
authors: Cornelis L
authors: CL
authors: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007370:Interferon Type I / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D007370:Interferon Type I