In silico Analyses of Skin and Peripheral Blood Transcriptional Data in Cutaneous Lupus Reveals CCR2-A Novel Potential Therapeutic Target

Cutaneous lesions feature prominently in lupus erythematosus (LE). Yet lupus and its cutaneous manifestations exhibit extraordinary clinical heterogeneity, making it imperative to stratify patients with varying organ involvement based on molecular criteria that may be of clinical value. We conducted several in silico bioinformatics-based analyses integrating chronic cutaneous lupus erythematosus (CCLE)-skin and blood expression profiles to provide novel insights into disease mechanisms and potential future therapy. In addition to substantiating well-known prominent apoptosis and interferon related response in both tissue environments, the overrepresentation of GO categories in the datasets, in the context of existing literature, led us to model a "disease road-map" demonstrating a coordinated orchestration of the autoimmune response in CCLE reflected in three phases: (1) initiation, (2) amplification, and (3) target damage in skin. Within this framework, we undertook in silico interactome analyses to identify significantly "over-connected" genes that are potential key functional players in the metabolic reprogramming associated with skin pathology in CCLE. Furthermore, overlapping and distinct transcriptional "hot spots" within CCLE skin and blood expression profiles mapping to specified chromosomal locations offer selected targets for identifying disease-risk genes. Lastly, we used a novel in silico approach to prioritize the receptor protein CCR2, whose expression level in CCLE tissues was validated by qPCR analysis, and suggest it as a drug target for use in future potential CCLE therapy.