{"doi":"10.1002/art.42615","title":"Shared and Distinctive Transcriptomic and Proteomic Pathways in Adult and Juvenile Dermatomyositis","abstract":"OBJECTIVE: Transcript and protein expression were interrogated to examine gene locus and pathway regulation in the peripheral blood of active adult dermatomyositis (DM) and juvenile DM patients receiving immunosuppressive therapies. METHODS: Expression data from 14 DM and 12 juvenile DM patients were compared to matched healthy controls. Regulatory effects at the transcript and protein level were analyzed by multi-enrichment analysis for assessment of affected pathways within DM and juvenile DM. RESULTS: 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-stimulated genes was elevated, including CXCL10, ISG15, OAS1, CLEC4A, and STAT1. Innate immune markers specific to neutrophil granules and neutrophil extracellular traps were up-regulated in both DM and juvenile DM, including BPI, CTSG, ELANE, LTF, MPO, and MMP8. Pathway analysis revealed up-regulation of PI3K/AKT, ERK, and p38 MAPK signaling, whose central components were broadly up-regulated in DM, while peripheral upstream and downstream components were differentially regulated in both DM and juvenile DM. Up-regulated 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-2 components, and numerous glycolytic enzymes. Pathways unique to DM included sirtuin signaling, aryl hydrocarbon receptor signaling, protein ubiquitination, and granzyme B signaling. CONCLUSION: The combination of proteomics and transcript expression by multi-enrichment analysis broadened the identification of up- and down-regulated 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.","journal":"Arthritis & Rheumatology","year":2023,"id":336274,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9389,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1066706,"name":"Mythri Ambatipudi","orcid":"0000-0002-7460-7492","position":1,"is_corresponding":false},{"id":315874,"name":"Terrance P. OʼHanlon","orcid":null,"position":2,"is_corresponding":false},{"id":587313,"name":"Michael A. Smith","orcid":"0009-0005-3694-3187","position":3,"is_corresponding":false},{"id":868733,"name":"Melissa de los Reyes","orcid":"0000-0002-6055-0413","position":4,"is_corresponding":false},{"id":264510,"name":"Adam Schiffenbauer","orcid":"0000-0001-9964-9966","position":5,"is_corresponding":false},{"id":491436,"name":"Saifur Rahman","orcid":null,"position":6,"is_corresponding":false},{"id":1067163,"name":"Kamelia Zerrouki","orcid":null,"position":7,"is_corresponding":false},{"id":247406,"name":"Frederick W. Miller","orcid":"0000-0003-2831-9593","position":8,"is_corresponding":false},{"id":490688,"name":"Miguel A. F. Sanjuán","orcid":"0000-0003-3515-0837","position":9,"is_corresponding":false},{"id":241283,"name":"Jian‐Liang Li","orcid":"0000-0002-6487-081X","position":10,"is_corresponding":false},{"id":304732,"name":"Kerry A. Casey","orcid":"0000-0001-7194-8585","position":11,"is_corresponding":false},{"id":264511,"name":"Lisa G. Rider","orcid":"0000-0002-6912-2458","position":12,"is_corresponding":false},{"id":35645,"name":"James M. Ward","orcid":"0000-0002-9510-2848","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:10:17.243221Z","pmid":"37229703","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}