This study investigates the gene expression patterns in blood leukocytes of patients with systemic lupus erythematosus (SLE) using oligonucleotide microarrays. The researchers found a homogeneous gene expression pattern in active SLE, characterized by overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using stringent statistical analysis, 15 genes were identified as highly up-regulated in SLE patients, 14 of which are targets of IFN, and one, defensin DEFA-3, is a major product of immature granulocytes. A more liberal statistical correction yielded 18 additional genes, 12 of which are IFN-regulated and 4 granulocyte-specific. The presence of immature neutrophils was confirmed in a significant fraction of SLE patients' white blood cells. High-dose glucocorticoids, a standard treatment for SLE flares, effectively shut down the IFN signature, further supporting the role of this cytokine in SLE pathogenesis. The expression of 10 genes correlated with disease activity according to the SLEDAI, with the formyl peptide receptor-like 1 protein showing the strongest correlation (P < 0.001, r = 0.55). The study highlights the central role of IFN in SLE and suggests that immature granulocytes may play a significant role in the disease's pathogenesis.This study investigates the gene expression patterns in blood leukocytes of patients with systemic lupus erythematosus (SLE) using oligonucleotide microarrays. The researchers found a homogeneous gene expression pattern in active SLE, characterized by overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using stringent statistical analysis, 15 genes were identified as highly up-regulated in SLE patients, 14 of which are targets of IFN, and one, defensin DEFA-3, is a major product of immature granulocytes. A more liberal statistical correction yielded 18 additional genes, 12 of which are IFN-regulated and 4 granulocyte-specific. The presence of immature neutrophils was confirmed in a significant fraction of SLE patients' white blood cells. High-dose glucocorticoids, a standard treatment for SLE flares, effectively shut down the IFN signature, further supporting the role of this cytokine in SLE pathogenesis. The expression of 10 genes correlated with disease activity according to the SLEDAI, with the formyl peptide receptor-like 1 protein showing the strongest correlation (P < 0.001, r = 0.55). The study highlights the central role of IFN in SLE and suggests that immature granulocytes may play a significant role in the disease's pathogenesis.