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Regulatory effects at the transcript and protein level were analyzed by multi\u2010enrichment analysis for assessment of affected pathways within DM and juvenile DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of 1,124 gene loci were significantly altered at the transcript or protein levels across DM or juvenile DM, with 70 genes shared. A subset of interferon\u2010stimulated genes was elevated, including CXCL10, ISG15, OAS1, CLEC4A, and STAT1. Innate immune markers specific to neutrophil granules and neutrophil extracellular traps were up\u2010regulated in both DM and juvenile DM, including BPI, CTSG, ELANE, LTF, MPO, and MMP8. Pathway analysis revealed up\u2010regulation of PI3K\/AKT, ERK, and p38 MAPK signaling, whose central components were broadly up\u2010regulated in DM, while peripheral upstream and downstream components were differentially regulated in both DM and juvenile DM. Up\u2010regulated components shared by DM and juvenile DM included cytokine:receptor pairs LGALS9:HAVCR2, LTF\/NAMPT\/S100A8\/HSPA1A:TLR4, CSF2:CSF2RA, EPO:EPOR, FGF2\/FGF8:FGFR, several Bcl\u20102 components, and numerous glycolytic enzymes. Pathways unique to DM included sirtuin signaling, aryl hydrocarbon receptor signaling, protein ubiquitination, and granzyme B signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of proteomics and transcript expression by multi\u2010enrichment analysis broadened the identification of up\u2010 and down\u2010regulated pathways among active DM and juvenile DM patients. These pathways, particularly those which feed into PI3K\/AKT and MAPK signaling and neutrophil degranulation, may be potential therapeutic targets.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42615-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42615","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T16:59:48Z","timestamp":1685033988000},"page":"2014-2026","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Shared and Distinctive Transcriptomic and Proteomic Pathways in Adult and Juvenile Dermatomyositis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-2848","authenticated-orcid":false,"given":"James M.","family":"Ward","sequence":"first","affiliation":[{"name":"Integrative Bioinformatics Support Group National Institute of Environmental Health Sciences, NIH, Research Triangle Park  North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7460-7492","authenticated-orcid":false,"given":"Mythri","family":"Ambatipudi","sequence":"additional","affiliation":[{"name":"Environmental Autoimmunity Group, Clinical Research Branch National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland and Research Triangle  Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrance P.","family":"O'Hanlon","sequence":"additional","affiliation":[{"name":"Environmental Autoimmunity Group, Clinical Research Branch National Institute of Environmental 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