Article Text

PDF
Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus
  1. M Nikpour1,
  2. A A Dempsey2,
  3. M B Urowitz1,
  4. D D Gladman1,
  5. D A Barnes3
  1. 1
    University of Toronto Lupus Clinic and the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada
  2. 2
    Xceed Molecular, Toronto, Ontairo, Canada
  3. 3
    Covance Laboratories, Chantilly, Virginia, USA
  1. M B Urowitz, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Room 1E-409, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8; m.urowitz{at}utoronto.ca

Abstract

Objective: To determine whether peripheral blood gene expression of patients with systemic lupus erythaematosus (SLE) correlates with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K).

Methods: RNA was isolated from peripheral blood of 269 patients with SLE and profiled on a custom microarray. Hierarchical clustering and a heat map were used to categorise samples into major clusters based on gene expression pattern. Correlates, including demographic and disease-related characteristics such as SLEDAI-2K score, of the major sample clusters were compared using multivariate regression models.

Results: A set of 31 interferon (IFN)-regulated genes were seen to be driving the separations of samples into two clusters, one characterised by a relatively high IFN-regulated gene signature (n = 150) and the other by a relatively low IFN-regulated gene signature (n = 119). Disease activity measured using the SLEDAI-2K was significantly correlated with the high IFN gene signature. In multivariate regression analysis the immunological component of the SLEDAI-2K was a significant correlate of the high IFN gene signature as was presence of antibodies to U1RNP. There were no discernable correlates of the 156 non-IFN regulated genes profiled on the custom array.

Conclusion: Peripheral blood gene expression profiling (GEP) in SLE allows patients to be categorised into two groups based on a high or low IFN gene signature. Disease activity measured using the SLEDAI-2K is correlated with the high IFN gene signature, indicating that GEP may be a useful biomarker of disease activity in SLE.

Statistics from Altmetric.com

Footnotes

  • Funding: This study was supported by Xceed Molecular. MN is supported by the Geoff Carr Lupus Fellowship.

  • Competing interests: None declared.

  • Ethics approval: The study was approved by the research ethics board of the University of Toronto Health Network and written informed consent was obtained from all participants.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.