The study by Baechler et al. investigates the gene expression profiles of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) to identify distinct patterns that distinguish SLE patients from healthy controls. They found that about half of the SLE patients showed dysregulated expression of genes in the interferon (IFN) pathway, which served as a marker for more severe disease involving the kidneys, hematopoietic cells, and/or the central nervous system. The study provides insights into the genetic pathways underlying SLE and identifies a subgroup of patients who may benefit from therapies targeting the IFN pathway. The results highlight the importance of gene expression profiling in peripheral blood cells for understanding and managing SLE.The study by Baechler et al. investigates the gene expression profiles of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) to identify distinct patterns that distinguish SLE patients from healthy controls. They found that about half of the SLE patients showed dysregulated expression of genes in the interferon (IFN) pathway, which served as a marker for more severe disease involving the kidneys, hematopoietic cells, and/or the central nervous system. The study provides insights into the genetic pathways underlying SLE and identifies a subgroup of patients who may benefit from therapies targeting the IFN pathway. The results highlight the importance of gene expression profiling in peripheral blood cells for understanding and managing SLE.