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Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus

¹ University of Toronto Lupus Clinic and the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada
² Xceed Molecular, Toronto, Ontairo, Canada
³ Covance Laboratories, Chantilly, Virginia, USA

Correspondence to:
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

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.