OP0082 Microarray and Mirna Analysis of Cutaneous Lupus: Differential Expression in Discoid Lupus Versus Subacute Lupus

BackgroundSkin involvement occurs in 70-85% of patients with LE and in up to 23-28% of patients represents the first sign of the systemic disease [1]. Discoid lupus erythematosus (DLE) and subacute cutaneous lupus CLE (SCLE) are the most prevalent subtypes but they are quite differents. DNA microarray technology has been used for the analysis of gene expression patterns in a variety of skin diseases. In CLE, to date, only one global microarray has been performed in lesional skin of patients with DLE showing a predominance of IFN-g-associated genes [2].ObjectivesThis study used simultaneously microarray and miRNA analysis to compare the patterns of gene expression id DLE versus SCLE to better characterize new aspects of their pathology, focusing mainly in the possible mechanisms implicated in the development of fibrosis/scarring, and identify potentially new targets that might be useful in the diagnosis and treatment of those two subtypes of CLE.MethodsPunch biopsies were taken from lesional and non-lesional skin of patients with moderate active DLE (n=10) and SCLE (n=10) and total mRNA and miRNA were extracted and purified for microarray analysis. To validate the results found in the microarray analysis, a new cohort of paraffin-embedded (FFPE) sample obtained from DLE (n=20) and SCLE (n=18) patients were evaluated by quantitative reserve transcription-PCR. The statistical analyses corresponding to microarrays were performed using the free statistical language R and the libraries developed for microarray data analysis by the Bioconductor Project.ResultsUp regulated pathways predominantly seen in DLE included mainly those involved in T-cell signalling, whereas in patients with SCLE included pathways mainly related with the innate immune system. Comparison of both conditions highlighted a predominance of several distinct pathways involving genes participating in the regulation of the Epithelial-Mesenchymal Transition pathway (EMT) and fibrosis in DLE samples. Quantitative reserve transcriptase-PCR (RT-PCR) confirmations supported increased cellular signatures of T cells (CD28, CD3D, CD4, CD8, FOX3P) and the implication of EMT pathway (MMP9, PAI-1, PDGFD, EGF). The miRNAs study reveals upregulation of miR-31 and miR-485-3p and downregulation of miR-31 in the DLE samples.ConclusionsOur data provide a global description of gene expression in DLE and SCLE skin and provide the main differences between the two types of lupus cutaneous: the T cell response and the