Common Patterns of Gene Expression in Tissues of Patients with Systemic Lupus Erythematosus Imply Similar Pathways of Molecular Pathogenesis

Abstract

Abstract The mechanisms underlying tissue pathology in SLE are not completely understood. To gain additional insight, gene expression profiles from lupus affected skin, synovium, and kidney were obtained and analyzed for commonalities. More than 300 arrays from lupus patients and controls were analyzed to determine differentially expressed (DE) genes (8279 discoid lupus skin, 5465 synovium, 6381 glomerulus, 5587 kidney tubulointerstitum). Notably, the majority of lupus tissue DE genes were detected in more than one tissue and 439 were differentially expressed in all tissues. Curated STRING-based interaction analysis of these 439 DE genes identified a number of functions and pathways that were commonly activated in all four tissues such as p38 MAPK and Ras signaling, T cell signaling, the IFN-signature, and hallmarks of antigen presentation. IPA identified 65 pathways shared among these tissues, including PI3K signaling, B cell receptor signaling, TLR signaling, IL-6 signaling, and T cell signaling. When DE genes in at least 3 of 4 tissues were examined, 1,379 and 1,066 genes that were commonly up-regulated and down-regulated, respectively, were identified. Curated STRING-based interaction analysis of the up-regulated genes in at least three of the four tissues identified several additional cellular and molecular processes, including neutrophil chemotaxis, T cell adhesion, DNA damage response, cell proliferation, and hallmarks of CD8+ T cells, monocytes, and Th2 cells. These results indicate that common cellular and molecular pathways can be identified in all of the affected lupus tissues, implying that related processes might be involved in the pathology of multiple organs in this autoimmune disease.