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

Mandana Nikpour ¹, Adam A. Dempsey ², Murray B Urowitz ^1*, Dafna D Gladman ¹ and Debra A. Barnes ²

¹ Toronto Western Hospital, Canada
² Xceed Molecular, United States

^* To whom correspondence should be addressed. E-mail: m.urowitz{at}utoronto.ca.

Accepted 17 November 2007

Abstract

Objective: To determine whether peripheral blood gene expression of patients with 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 categorize 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 characterized 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 SLEDAI-2K was significantly correlated with the high IFN gene signature. In multivariate regression analysis the immunologic component of 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 categorized into two groups based on a high or low IFN gene signature. Disease activity measured using SLEDAI-2K is correlated with the high IFN gene signature, indicating that GEP may be a useful biomarker of disease activity in SLE.

Keywords: Systemic Lupus Erythematosus, disease activity, gene expression, microarray, peripheral blood

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