{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:51:58Z","timestamp":1788997918801,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is a chronic inflammatory skin disease driven by genetic, environmental, and immune factors. While biologics like adalimumab (anti-TNF\u03b1) 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\u03b1 (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\u2013protein 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\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms26178118","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:31:26Z","timestamp":1755865886000},"page":"8118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic Identification of Immune-Related Hubs as Candidate Predictor Biomarkers of Therapeutic Response in Psoriasis"],"prefix":"10.3390","volume":"26","author":[{"given":"Elisabet","family":"Cant\u00f3","sequence":"first","affiliation":[{"name":"Group of Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Elena","family":"del Prado","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Hospital Quir\u00f3nsalud, 50012 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Vilarrasa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-963X","authenticated-orcid":false,"given":"Anna","family":"L\u00f3pez-Ferrer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Garc\u00eda Latasa de Aran\u00edbar","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Hospital Royo Villanova, 50015 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-9861","authenticated-orcid":false,"given":"Maria Angels","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Group of Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-7159","authenticated-orcid":false,"given":"Marta","family":"Gut","sequence":"additional","affiliation":[{"name":"Centro Nacional de Analisis Genomico (CNAG), 08028 Barcelona, Spain"},{"name":"Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-3291","authenticated-orcid":false,"given":"Maria","family":"Mulet","sequence":"additional","affiliation":[{"name":"Group of Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0361-2873","authenticated-orcid":false,"given":"Anna","family":"Esteve-Codina","sequence":"additional","affiliation":[{"name":"Centro Nacional de Analisis Genomico (CNAG), 08028 Barcelona, Spain"},{"name":"Universitat de Barcelona (UB), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-4405","authenticated-orcid":false,"given":"Ruben","family":"Osuna-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Group of Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0233-5595","authenticated-orcid":false,"given":"Albert","family":"Guinart-Cuadra","sequence":"additional","affiliation":[{"name":"Group of Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-0952","authenticated-orcid":false,"given":"Lu\u00eds","family":"Puig","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-6682","authenticated-orcid":false,"given":"Silvia","family":"Vidal","sequence":"additional","affiliation":[{"name":"Group of Inflammatory Diseases, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain"},{"name":"Department of Cellular Biology, Fisiologia i Immunologia, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1159\/000104261","article-title":"Experimental Koebner Phenomenon in Patients with Psoriasis","volume":"215","author":"Kalayciyan","year":"2007","journal-title":"Dermatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1046\/j.1523-1747.2001.01340.x","article-title":"Cutaneous Injury Induces the Release of Cathelicidin AntiMicrobial Peptides Active Against Group A Streptococcus","volume":"117","author":"Dorschner","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"ii87","DOI":"10.1136\/ard.2004.032276","article-title":"Psoriasis treatment: Current and emerging directed therapies","volume":"64","author":"Winterfield","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","first-page":"988","article-title":"Effect of adalimumab on gene expression profiles of psoriatic","volume":"15","author":"Chow","year":"2016","journal-title":"J. Drugs Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nm.3895","article-title":"IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases","volume":"21","author":"Teng","year":"2015","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature06116","article-title":"Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide","volume":"449","author":"Lande","year":"2007","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lu, J., Wang, Y., Li, Y., Zhong, X., Gong, Y., Ding, Y., Yu, N., and Shi, Y. (2022). Based on Gene Expression Analysis: Low-Density Neutrophil Expression Is a Characteristic of the Fast Responders Treated With Guselkumab for Psoriasis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.865875"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.jaci.2021.07.024","article-title":"Cytokine responses in nonlesional psoriatic skin as clinical predictor to anti-TNF agents","volume":"149","author":"Tsoi","year":"2022","journal-title":"J. Allergy. Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/09546634.2014.880775","article-title":"Efficacy of adalimumab in the treatment of moderate-to-severe psoriasis: A retrospective study of 100 patients in daily practice","volume":"26","author":"Armesto","year":"2015","journal-title":"J. Dermatol. Treat"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ruiz-Villaverde, R., Vasquez-Chinchay, F., Rodriguez-Fernandez-Freire, L., C. Armario-Hita, J., Perez-Gil, A., and Galan-Gutierrez, M. (2022). Super-Responders in Moderate-Severe Psoriasis under Guselkumab Treatment: Myths, Realities and Future Perspectives. Life, 12.","DOI":"10.3390\/life12091412"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Albanesi, C., Madonna, S., Gisondi, P., and Girolomoni, G. (2018). The Interplay Between Keratinocytes and Immune Cells in the Pathogenesis of Psoriasis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01549"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Su, W., Wei, Y., Huang, B., and Ji, J. (2021). Identification of Hub Genes and Immune Infiltration in Psoriasis by Bioinformatics Method. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.606065"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12967-023-03923-z","article-title":"Identification of novel immune subtypes and potential hub genes of patients with psoriasis","volume":"21","author":"Li","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_14","first-page":"225","article-title":"Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis","volume":"20","author":"Zhang","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Deng, W., Yan, Y., Shi, C., and Sui, D. (2024). Single-cell and bulk RNAseq unveils the immune infiltration landscape and targeted therapeutic biomarkers of psoriasis. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1365273"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3892\/ijmm.2020.4771","article-title":"Transcriptomic landscaping of core genes and pathways of mild and severe psoriasis vulgaris","volume":"47","author":"Choudhary","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1016\/j.jaci.2020.11.028","article-title":"Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8(+) T cells in autoimmunity and cancer","volume":"147","author":"Liu","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00403-009-0966-2","article-title":"Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions","volume":"302","author":"Chen","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1172\/JCI110409","article-title":"Involved and Uninvolved Skin from Psoriatic Subjects","volume":"68","author":"Krueger","year":"1981","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1038\/jid.2009.173","article-title":"Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin","volume":"129","author":"Gudjonsson","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/jid.2011.24","article-title":"TNF-alpha downregulates filaggrin and loricrin through c-Jun N-terminal kinase: Role for TNF-alpha antagonists to improve skin barrier","volume":"131","author":"Kim","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Szel, E., Bozo, R., Hunyadi-Gulyas, E., Manczinger, M., Szabo, K., Kemeny, L., Bata-Csorgo, Z., and Groma, G. (2019). Comprehensive Proteomic Analysis Reveals Intermediate Stage of Non-Lesional Psoriatic Skin and Points out the Importance of Proteins Outside this Trend. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-47774-5"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1016\/j.jaci.2018.11.042","article-title":"Psoriatic skin molecular and histopathologic profiles after treatment with risankizumab versus ustekinumab","volume":"143","author":"Visvanathan","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Liu, L., Liu, W., Zheng, Y., Chen, J., Zhou, J., Dai, H., Cai, S., Liu, J., Zheng, M., and Ren, Y. (2019). Anti-TNF-\u03b1 treatment-related pathways and biomarkers revealed by transcriptome analysis in Chinese psoriasis patients. BMC Syst. Biol., 13.","DOI":"10.1186\/s12918-019-0698-7"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/bjd.13128","article-title":"Regulated genes in psoriatic skin during treatment with fumaric acid esters","volume":"171","author":"Onderdijk","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/bjd.12355","article-title":"Markers of systemic inflammation in psoriasis: A systematic review and meta-analysis","volume":"169","author":"Dowlatshahi","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e12846","DOI":"10.1111\/sji.12846","article-title":"The CCL20 and CCR6 axis in psoriasis","volume":"91","author":"Furue","year":"2020","journal-title":"Scand. J. Immunol"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ainali, C., Valeyev, N., Perera, G., Williams, A., Gudjonsson, J.E., Ouzounis, C.A., Nestle, F.O., and Tsoka, S. (2012). Transcriptome classification reveals molecular subtypes in psoriasis. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-472"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1038\/jid.2009.65","article-title":"Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: Implications for psoriasis pathogenesis","volume":"129","author":"Harper","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.advms.2015.07.011","article-title":"CXCL10 in psoriasis","volume":"60","author":"Ferrari","year":"2015","journal-title":"Adv. Med. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature14452","article-title":"Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation","volume":"523","author":"Gagliani","year":"2015","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1365-3083.2010.02432.x","article-title":"Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation","volume":"72","author":"Jager","year":"2010","journal-title":"Scand. J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jaci.2014.01.025","article-title":"Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis","volume":"133","author":"Sofen","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W147","DOI":"10.1093\/nar\/gkw419","article-title":"Heatmapper: Web-enabled heat mapping for all","volume":"44","author":"Babicki","year":"2016","journal-title":"Nucleic. Acids. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Antonatos, C., Koskeridis, F., Ralliou, C.M., Evangelou, E., Grafanaki, K., Georgiou, S., Tsilidis, K.K., Tzoulaki, I., and Vasilopoulos, Y. (2024). A polygenic risk score model for psoriasis based on the protein interactions of psoriasis susceptibility loci. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1451679"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1186\/1752-0509-8-S4-S11","article-title":"cytoHubba: Identifying hub objects and subnetworks from complex interactome","volume":"8","author":"Chin","year":"2014","journal-title":"BMC Syst. Biol."},{"key":"ref_39","unstructured":"Wickham, H., Navarro, D., and Pedersen, T.L. (2016). Ggplot2: Elegant Graphics for Data Analysis (3e), Springer."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:39Z","timestamp":1760034819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":39,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178118"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178118","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]}}}