Systemic lupus erythematosus (SLE) is a complex, inflammatory autoimmune disease that affects multiple organ systems. Researchers used global gene expression profiling of peripheral blood mononuclear cells (PBMCs) to identify distinct gene expression patterns that distinguish SLE patients from healthy controls. They found that about half of the patients had dysregulated expression of genes in the interferon (IFN) pathway. This IFN gene expression signature served as a marker for more severe disease involving the kidneys, hematopoietic cells, and the central nervous system (CNS). These findings suggest that SLE is a complex genetic disease with multiple genes influencing the clinical phenotype. The study analyzed gene expression in PBMCs from 48 SLE patients and 42 healthy controls. They identified 161 genes that were differentially expressed, with most showing higher expression in SLE patients. These genes included those involved in immune responses, such as cell surface markers, adhesion molecules, and cytokine pathways. Additionally, genes in the IFN pathway were found to be dysregulated in about half of the patients. The IFN gene expression signature was correlated with more severe disease, as patients with higher IFN scores had more severe clinical manifestations, including kidney and CNS involvement, and hematologic complications. The study also found that IFN-regulated genes were significantly upregulated in SLE patients, with 23 of the 161 genes identified as IFN-regulated. These genes included those involved in innate and acquired immunity. The IFN score, calculated based on gene expression levels, was significantly correlated with the number of SLE disease criteria and the severity of clinical manifestations. Patients with higher IFN scores were more likely to have severe disease involving the kidneys, CNS, and hematologic complications. The study highlights the importance of gene expression profiling in understanding the pathophysiology of SLE and identifying potential therapeutic targets. The findings suggest that targeting the IFN pathway may be beneficial for patients with severe SLE. The study also indicates that gene expression profiling in peripheral blood cells may be useful for identifying relevant disease pathways in other autoimmune and inflammatory disorders.Systemic lupus erythematosus (SLE) is a complex, inflammatory autoimmune disease that affects multiple organ systems. Researchers used global gene expression profiling of peripheral blood mononuclear cells (PBMCs) to identify distinct gene expression patterns that distinguish SLE patients from healthy controls. They found that about half of the patients had dysregulated expression of genes in the interferon (IFN) pathway. This IFN gene expression signature served as a marker for more severe disease involving the kidneys, hematopoietic cells, and the central nervous system (CNS). These findings suggest that SLE is a complex genetic disease with multiple genes influencing the clinical phenotype. The study analyzed gene expression in PBMCs from 48 SLE patients and 42 healthy controls. They identified 161 genes that were differentially expressed, with most showing higher expression in SLE patients. These genes included those involved in immune responses, such as cell surface markers, adhesion molecules, and cytokine pathways. Additionally, genes in the IFN pathway were found to be dysregulated in about half of the patients. The IFN gene expression signature was correlated with more severe disease, as patients with higher IFN scores had more severe clinical manifestations, including kidney and CNS involvement, and hematologic complications. The study also found that IFN-regulated genes were significantly upregulated in SLE patients, with 23 of the 161 genes identified as IFN-regulated. These genes included those involved in innate and acquired immunity. The IFN score, calculated based on gene expression levels, was significantly correlated with the number of SLE disease criteria and the severity of clinical manifestations. Patients with higher IFN scores were more likely to have severe disease involving the kidneys, CNS, and hematologic complications. The study highlights the importance of gene expression profiling in understanding the pathophysiology of SLE and identifying potential therapeutic targets. The findings suggest that targeting the IFN pathway may be beneficial for patients with severe SLE. The study also indicates that gene expression profiling in peripheral blood cells may be useful for identifying relevant disease pathways in other autoimmune and inflammatory disorders.