4b8e1e0f0d50da08e181e9a802e6a302 ijms-26-08118.pdf 2149232cbf932811d5bcb09ed9e6b1bbf70fe982 ijms-26-08118.pdf 2b6997bac29701a836197b7de2ecfa234dd2341079e0bb799cc1f6bee686a6b8 ijms-26-08118.pdf Title: Transcriptomic Identification of Immune-Related Hubs as Candidate Predictor Biomarkers of Therapeutic Response in Psoriasis Subject: Psoriasis is a chronic inflammatory skin disease driven by genetic, environmental, and immune factors. While biologics like adalimumab (anti-TNF) and risankizumab (anti-IL-23) have improved outcomes, patient response variability remains unclear. This study examined immune-related transcriptomic differences between lesional (L) and non-lesional (NL) psoriatic skin, focusing on immune-related hub genes, their plasma levels, and their correlations with severity and treatment response. Patients with moderate-to-severe psoriasis were enrolled before treatment with anti-TNF (n = 16) or anti-IL-23 (n = 18). Plasma and paired L and NL skin biopsies were collected for RNA sequencing. Gene ontology enrichment analysis found four immune-related terms enriched in L skin: T-helper 17, granulocyte and lymphocyte chemotaxis, and antimicrobial humoral response. A protein–protein interaction network identified ten immune-related hub genes upregulated in L skin that correlated with clinical severity. Patients with prior treatments expressed distinctive gene profiles. Plasma levels of CCL20 strongly correlated with disease severity. Decision tree models identified CCL20 expression in skin and plasma levels of IL-6 and CXCL8 as candidate predictors for anti-TNF response. Similarly, skin expression of CXCL8, IL-6, and CXCL10, alongside plasma levels of CCL20, IL-6, and CXCL8, may predict anti-IL-23 response. Ten immune-related hubs may serve as possible biomarkers for disease severity and therapeutic response in psoriasis. Keywords: psoriasis; transcriptomic; inflammation; hubs; biomarkers Author: Elisabet Cantó, María Elena del Prado, Eva Vilarrasa, Anna López-Ferrer, Francisco Javier García Latasa de Araníbar, Maria Angels Ortiz, Marta Gut, Maria Mulet, Anna Esteve-Codina, Ruben Osuna-Gómez, Albert Guinart-Cuadra, Luís Puig and Silvia Vidal Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Fri Aug 22 12:04:29 2025 CEST ModDate: Fri Aug 22 12:09:03 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 12059045 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MIKRSI+VnURWPalladioL Type 1 Custom yes yes yes 136 0 RUNWZP+URWPalladioL-Ital Type 1 Custom yes yes yes 137 0 JJQMGE+URWPalladioL-Bold Type 1 Custom yes yes yes 138 0 NYMSZW+URWPalladioL-Roma Type 1 Custom yes yes yes 139 0 GOCQIR+EURM10 Type 1 Builtin yes yes yes 140 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 302 0 CZOINJ+EURB10 Type 1 Builtin yes yes yes 303 0 KXDJCR+CMSY10 Type 1 Builtin yes yes yes 304 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 190 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 323 0 GPDAOJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 324 0 IOLAWT+PazoMath-Italic Type 1 Builtin yes yes yes 548 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 441 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 537 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 612 0 GPDAOJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 613 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 643 0 GPDAOL+PalatinoLinotype TrueType WinAnsi yes yes no 663 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-11-22 04:17:27 CET RepresentationInformation: ijms-26-08118.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-11-21 19:00:09 CET Size: 12059045 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 860 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: Patient Demographics Item: Title: Identification of DEGs in L vs. NL Skin Item: Title: Identification of Skin Immune Hub Genes Item: Title: Previous Treatment Conditioned Differential Skin DEGs and Skin Immune Hubs Expression Item: Title: Response to Anti-TNF Item: Title: Response to Anti-IL-23 Item: Title: Plasma Immune Hubs and Their Relationships with Clinical Psoriasis Characteristics Item: Title: Plasma Immune Hub Expression Conditions Anti-TNF and Anti-IL-23 Response Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Patient Cohort and Samples Item: Title: RNA Sequencing Item: Title: Functional Enrichment Analysis Item: Title: Protein–Protein Interaction (PPI) Network Construction and Immune-Related Hub Genes Item: Title: ELISAs Item: Title: Statistical Analysis Item: Title: References Info: Title: Transcriptomic Identification of Immune-Related Hubs as Candidate Predictor Biomarkers of Therapeutic Response in Psoriasis Author: Elisabet Cantó, María Elena del Prado, Eva Vilarrasa, Anna López-Ferrer, Francisco Javier García Latasa de Araníbar, Maria Angels Ortiz, Marta Gut, Maria Mulet, Anna Esteve-Codina, Ruben Osuna-Gómez, Albert Guinart-Cuadra, Luís Puig and Silvia Vidal Subject: Psoriasis is a chronic inflammatory skin disease driven by genetic, environmental, and immune factors. While biologics like adalimumab (anti-TNF) and risankizumab (anti-IL-23) have improved outcomes, patient response variability remains unclear. This study examined immune-related transcriptomic differences between lesional (L) and non-lesional (NL) psoriatic skin, focusing on immune-related hub genes, their plasma levels, and their correlations with severity and treatment response. Patients with moderate-to-severe psoriasis were enrolled before treatment with anti-TNF (n = 16) or anti-IL-23 (n = 18). Plasma and paired L and NL skin biopsies were collected for RNA sequencing. Gene ontology enrichment analysis found four immune-related terms enriched in L skin: T-helper 17, granulocyte and lymphocyte chemotaxis, and antimicrobial humoral response. A protein–protein interaction network identified ten immune-related hub genes upregulated in L skin that correlated with clinical severity. Patients with prior treatments expressed distinctive gene profiles. Plasma levels of CCL20 strongly correlated with disease severity. Decision tree models identified CCL20 expression in skin and plasma levels of IL-6 and CXCL8 as candidate predictors for anti-TNF response. Similarly, skin expression of CXCL8, IL-6, and CXCL10, alongside plasma levels of CCL20, IL-6, and CXCL8, may predict anti-IL-23 response. Ten immune-related hubs may serve as possible biomarkers for disease severity and therapeutic response in psoriasis. 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