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


CONCLUSIONS
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.
University of Toronto Lupus Clinic and Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada.
M
M
Nikpour
A A
AA
Dempsey
M B
MB
Urowitz
D D
DD
Gladman
D A
DA
Barnes
D000208:Acute Disease; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D003165:Complement System Proteins / Q000032:analysis; D003430:Cross-Sectional Studies; D004247:DNA / Q000276:immunology; D015342:DNA Probes / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000502:physiology*; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
D001323:Autoantibodies; D015342:DNA Probes; D003165:Complement System Proteins; D004247:DNA; D007372:Interferons