The type I IFN signature as a biomarker of preclinical rheumatoid arthritis

Ann Rheum Dis. 2013 May;72(5):776-80. doi: 10.1136/annrheumdis-2012-202753. Epub 2013 Feb 23.

Abstract

Objectives: To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development.

Method: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / epidemiology
  • Biomarkers / blood
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon Type I / blood*
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Predictive Value of Tests
  • Proportional Hazards Models
  • ROC Curve
  • Risk Factors
  • Sweden / epidemiology

Substances

  • Biomarkers
  • Interferon Type I