Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease 
characterized by flares of high morbidity. Using oligonucleotide microarrays, we 
now show that active SLE can be distinguished by a remarkably homogeneous gene 
expression pattern with overexpression of granulopoiesis-related and interferon 
(IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni 
correction), 15 genes were found highly up-regulated in SLE patients, 14 of 
which are targets of IFN and one, defensin DEFA-3, a major product of immature 
granulocytes. A more liberal correction (Benjamini and Hochberg correction) 
yielded 18 additional genes, 12 of which are IFN-regulated and 4 
granulocyte-specific. Indeed immature neutrophils were identified in a large 
fraction of SLE patients white blood cells. High dose glucocorticoids, a 
standard treatment of disease flares, shuts down the interferon signature, 
further supporting the role of this cytokine in SLE. The expression of 10 genes 
correlated with disease activity according to the SLEDAI. The most striking 
correlation (P < 0.001, r = 0.55) was found with the formyl peptide 
receptor-like 1 protein that mediates chemotactic activities of defensins. 
Therefore, while the IFN signature confirms the central role of this cytokine in 
SLE, microarray analysis of blood cells reveals that immature granulocytes may 
be involved in SLE pathogenesis.