{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:41:49Z","timestamp":1759898509657,"version":"build-2065373602"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","award":["RF-2016-02361048"],"award-info":[{"award-number":["RF-2016-02361048"]}],"id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014805","name":"Roche Italia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Oligoarthritis, the most common form of Juvenile Idiopathic Arthritis in Western countries and a leading cause of disability, exhibits a variable clinical course. Early identification of children at risk of polyarticular extension is critical for guiding targeted therapy, but requires new biomarkers. This study aimed at profiling T cell and monocyte\/macrophage (MM) subset composition and activation\/maturation state combined with extracellular vesicle (EV) surface markers in synovial fluid (SF) and peripheral blood (PB) from new-onset Oligoarthritis patients to prospectively evaluate their correlation with clinical course over a two-year follow-up period and identify potential prognostic biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SF and PB samples were collected from 42 untreated patients at disease onset. Immune cell subsets were analyzed by flow cytometry, EV marker expression profiles by bead-based multiplex assays, and soluble TREM1 (sTREM1) levels by ELLA. Differences between patients exhibiting oligoarticular course (Group 1) or polyarticular extension (Group 2) over two years of follow-up were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Group 2 patients showed significantly higher CD3:CD14 ratio (AUC\u00a0=\u00a00.831,p&amp;lt;0.005) and HLA-DR+ CD4+ T cell percentages (64.8%vs52.5%,p=0.02) in SF compared to Group 1 patients. In PB, both HLA-DR+CD4+ and HLA-DR+CD8+ cells were significantly increased (AUC\u00a0=\u00a00.946,p&amp;lt;0.001) in Group 2. Group 2 patients also exhibited significantly higher proportions of effector memory (EM) CD4+ (AUC\u00a0=\u00a00.911, p&amp;lt;0.001) and CD8+ (AUC:0.929, p&amp;lt;0.001) subsets, along with lower proportions of na\u00efve CD4+ (AUC\u00a0=\u00a00.929, p&amp;lt;0.001) and CD8+ (AUC\u00a0=\u00a00.893, p&amp;lt;0.001) subsets in the circulation, that was reflected in a significantly higher EM:na\u00efve ratios for both CD4+ (AUC\u00a0=\u00a00.893,p&amp;lt;0.001) and CD8+ (AUC\u00a0=\u00a00.946;p&amp;lt;0.001) populations. TREM1+ CD14+ cell percentages in both SF and PB were significantly (p&amp;lt;0.05) lower (SF: 83.6%vs90.47%; PB:40.16%vs53.21%), while sTREM1 levels higher (SF: 8926vs5822 pg\/ml; PB:298.8vs232 pg\/ml), in Group 2 compared to Group 1. Finally, SF-derived EVs from Group 2 showed significantly reduced HLA-ABC (AUC\u00a0=\u00a00.857,p=0.012) and CD3 (AUC\u00a0=\u00a00.949,p&amp;lt;0.001) expression. Combining these markers further improved the discriminatory performance of the models (AUC\u00a0=\u00a01,p&amp;lt;0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This exploratory study identifies novel immune classifiers combining T lymphocytes and MM subsets with EV markers which stratify, at onset, Oligoarthritis patients who will develop polyarticular extension and provide important mechanistic insights into arthritis progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1663663","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:16:54Z","timestamp":1759897014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Immune biomarkers for the early stratification of oligoarthritis patients at risk of developing polyarticular 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