Differential gene expression analysis in CCLE lesions provides new insights regarding the genetics basis of skin vs. systemic disease.

Lupus erythematosus is a heterogeneous autoimmune condition affecting multiple organs including skin, which remains poorly understood. To investigate pathogenetic processes relevant to cutaneous lupus as compared to systemic disease, we generated genome-wide expression data from lesional and non-lesional skin of chronic cutaneous LE (CCLE) patients. We reveal LE skin-associated transcriptional profiles and identify prominent functional pathways. A subset of CCLE differentially expressed genes (DEGs) was found to overlap with systemic lupus, including those linked to interferon and apoptosis. We identified 13 skin associated transcriptional "hot spots" that represent activated chromosomal regions. Seventeen CCLE DEGs (eight within "hot spots") were found to overlap with previously reported SLE-associated susceptibility loci. Additionally, we identify chromosomal regions not previously associated with lupus, potentially harboring distinct susceptibility loci for CCLE. This study suggests that overlapping as well as distinct genetic factors underlie disease pathogenesis in systemic and cutaneous lupus.