104 Comparative transcriptomic profiles of cutaneous sarcoidosis and granuloma annulare

Background: Cutaneous sarcoidosis (CS) and granuloma annulare (GA) are chronic granulomatous skin diseases which are often refractory to therapy. The goal of this study was to identify key regulatory pathways and gene function networks in GA and CS to determine expression patterns differentiating these conditions. Methods: RNA-seq was performed on skin biopsies of CS (n=13), and GA (n=22). Differential analysis was performed on the entire transcriptomic profiles of each group. Results: Although the transcriptomic profiles of GA and CS samples had similarities, there were notable differences between these groups which may elucidate unique pathways that differentiate each disease. Our differential analysis identified 408 genes highly expressed in CS samples and 328 genes highly expressed in GA samples with p value ≤ 0.001 and log2 fold change ≥ 1. The highly expressed genes in GA samples were involved in the pathways including cellular glucuronidation, keratinization and keratinocyte differentiation, establishment of skin barrier, extracellular matrix disassembly. The most highly expressed pathways in CS group were those involving immune and inflammatory response, tryptophan catabolic process, T cell proliferation, response to interferon-gamma, and signal transduction. The top 10 significantly expressed genes in CS and GA are CD38, ITGAL, PRSS21, FMO1, SLC6A7, KAL1, CD22, CD6, DPEP1, GRAMD1B and CTTNBP2, GFRA2, VWC2, PLP1, GPSM2, ELL3, PLCD3, PCSK2, SLC6A15, MUC12, respectively. Conclusion: Our comparative transcriptome findings pinpoints disease-specific enrichment pathways and gene functions in CS and GA patients, which may shed light on different molecular mechanisms that contribute to disease progress. The top differential genes represent potential drug targets to develop novel therapies for these chronic granulomatous disorders.