Abstract
Background Pathomechanism of dermatomyositis (DM) remains yet fully elucidated. While several cytokines have been proved to participate in the progress of DM, few studies provided a comprehensive analysis of cytokinome in different DM clinical-serological subgroups and correlation with disease activity as well as interaction with DM tissue lesions.Methods Transcriptome datasets of DM skin and muscle were obtained from public database. Hub genes and signaling pathways were filtered by bioinformatic software. Serum cytokinome was measured in DM patients with different clinical-serological subgroups and correlation with disease activity indicators was analyzed. Cytokine interaction network was constructed.Results 6 hub genes, including STAT1, MX1, ISG15, IFIT3, GBP1 and OAS2 were identified as IFN signature in DM. Differently expressed genes (DEGs) identified in the skin and muscle datasets were significantly enriched in the type I interferon signaling pathway, defense response to virus and chemotaxis. 11 cytokines were significantly elevated in patients positive for melanoma differentiation-associated protein (MDA5) antibody. IFN-α, IFN-γ, MIP-1α, IP-10, MCP1, GRO-α, IL-6, IL-18 and IL-1RA were correlated with disease activity. MCP1/MIP-1α/RANTES/MCP2/CCR1 axes were filtered from cytokine interaction network.Conclusions The complexity of DM immunopathogenesis is mediated through interactions of multiple cytokines and signaling pathways. Type I interferon is the core participant in DM tissue damage. Serum upregulation of IFN-α, IFN-γ, MIP-1α, IP-10, MCP1, GRO-α, IL-6, IL-18 and IL-1RA could be used for disease activity assessment in DM patients positive for MDA5 antibody. Finally, MCP1/MIP-1α/RANTES/MCP2/CCR1 axes mediated monocytes attraction might be novel therapeutic targets in DM by chemokine network analysis.
Investigation of molecular mechanisms using integrated analysis of transcriptomes and cytokinome in dermatomyositis