Genomic Investigation of Lupus in the Skin

Abstract

Lupus erythematosus is a chronic autoimmune disorder with a protean clinical manifestation affecting virtually every organ including skin, with tremendous variation between patients. This makes it vital to stratify patients on a molecular basis. We used gene microarray technology for large-scale screening combined with bioinformatics to investigate global patterns of gene expression in cutaneous lupus erythematosus to allow further insights into disease heterogeneity. Unbiased clustering exposed a clear separation between cutaneous lupus erythematosus skin and blood samples. Pathway-based analyses of the differentially expressed genes from sample groups within skin and blood showed prominent apoptosis and interferon response signals. Given their well-known role in systemic lupus, the two processes are potentially critical to cutaneous lupus erythematosus as well. We found both coincident and distinct features between systemic lupus and cutaneous lupus erythematosus, as well as several pathways and processes that are specific to the cutaneous disease that offer potential therapeutic choices in the future. Finally, we identified shared cutaneous lupus erythematosus-skin and -blood transcriptional “hot spots” located on the genome that include several differentially expressed genes previously associated with the systemic disease. The differentially expressed genes included in the hot spots with no systemic lupus associations can potentially be targeted in future studies aimed at identifying risk genes related to cutaneous disease.