{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:39:37Z","timestamp":1792633177706,"version":"4.5.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biomark Res"],"DOI":"10.1186\/s40364-026-01029-4","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:16:29Z","timestamp":1792631789000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ex vivo JAK and TNF inhibitor\u2013modulated immune signatures guide first-line therapy selection in rheumatoid arthritis"],"prefix":"10.1186","volume":"14","author":[{"given":"Sagrario","family":"Corrales","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Cerd\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Merlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Malvar-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mu\u00f1oz-Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Sanchez-Pareja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Formanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Moreno-Ca\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Ortega-Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerusal\u00e9n","family":"Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Aranda-Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Ladehesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Font","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Carmen","family":"Abalos-Aguilera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desir\u00e9e","family":"Ruiz-Vilchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00aa \u00c1ngeles","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Barbarroja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta E.","family":"Alarcon-Riquelme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Escudero-Contreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chary","family":"L\u00f3pez-Pedrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"10055","key":"1029_CR1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/s0140-6736(16)30173-8","volume":"388","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. Elsevier BV. 2016;388(10055):2023\u201338. https:\/\/doi.org\/10.1016\/s0140-6736(16)30173-8.","journal-title":"Lancet. Elsevier BV"},{"key":"1029_CR2","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2018.13103","volume-title":"Diagnosis and management of rheumatoid arthritis: a review","author":"D Aletaha","year":"2018","unstructured":"Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 320. American Medical Association (AMA); 2018. p. 1360. https:\/\/doi.org\/10.1001\/jama.2018.13103."},{"issue":"17","key":"1029_CR3","doi-asserted-by":"publisher","first-page":"9534","DOI":"10.3390\/ijms22179534","volume":"22","author":"H Tsuchiya","year":"2021","unstructured":"Tsuchiya H, Fujio K. Title current status of the search for biomarkers for optimal therapeutic drug selection for patients with rheumatoid arthritis. IJMS. 2021;22(17):9534. https:\/\/doi.org\/10.3390\/ijms22179534.","journal-title":"IJMS"},{"key":"1029_CR4","doi-asserted-by":"publisher","unstructured":"Zhao J, Guo S, Schrodi SJ, He D. Molecular and cellular heterogeneity in rheumatoid arthritis: mechanisms and clinical implications. Front Immunol. 2021 [cited 2025 July 16]; 12. https:\/\/doi.org\/10.3389\/fimmu.2021.790122.","DOI":"10.3389\/fimmu.2021.790122"},{"key":"1029_CR5","doi-asserted-by":"publisher","unstructured":"Rivellese F, Nerviani A, Giorli G, Warren L, Jaworska E, Bombardieri M, et al. Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials. Lancet Rheumatol. 2023;5(11):e648\u201359. https:\/\/doi.org\/10.1016\/S2665-9913(23)00241-2.","DOI":"10.1016\/S2665-9913(23)00241-2"},{"issue":"6","key":"1029_CR6","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.ard.2026.01.023","volume":"85","author":"JS Smolen","year":"2026","unstructured":"Smolen JS, Edwards CJ, Konzett V, Laskou F, Aletaha D, Caporali R, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. Ann Rheumatic Dis. 2026;85(6):991\u20131009. https:\/\/doi.org\/10.1016\/j.ard.2026.01.023.","journal-title":"Ann Rheumatic Dis"},{"issue":"3","key":"1029_CR7","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s40744-020-00211-w","volume":"7","author":"E Sullivan","year":"2020","unstructured":"Sullivan E, Kershaw J, Blackburn S, Mahajan P, Boklage SH. Biologic disease-modifying antirheumatic Drug prescription patterns among Rheumatologists in Europe and Japan. Rheumatol Ther. 2020;7(3):517\u201335. https:\/\/doi.org\/10.1007\/s40744-020-00211-w.","journal-title":"Rheumatol Ther"},{"issue":"12","key":"1029_CR8","doi-asserted-by":"publisher","first-page":"3856","DOI":"10.1002\/art.37691","volume":"64","author":"A Yarilina","year":"2012","unstructured":"Yarilina A, Xu K, Chan C, Ivashkiv LB. Regulation of inflammatory responses in tumor necrosis factor\u2013activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheumatism. 2012;64(12):3856\u201366. https:\/\/doi.org\/10.1002\/art.37691.","journal-title":"Arthritis Rheumatism"},{"issue":"8","key":"1029_CR9","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.3390\/cells10081860","volume":"10","author":"L Roszkowski","year":"2021","unstructured":"Roszkowski L, Ciechomska M. Tuning monocytes and macrophages for personalized therapy and diagnostic challenge in rheumatoid arthritis. Cells. MDPI AG. 2021;10(8):1860. https:\/\/doi.org\/10.3390\/cells10081860.","journal-title":"Cells. MDPI AG"},{"key":"1029_CR10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jaut.2017.04.007","volume":"82","author":"C P\u00e9rez-S\u00e1nchez","year":"2017","unstructured":"P\u00e9rez-S\u00e1nchez C, Ruiz-Lim\u00f3n P, Aguirre MA, Jim\u00e9nez-G\u00f3mez Y, Arias-de la Rosa I, \u00c1balos-Aguilera MC, et al. Diagnostic potential of NETosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in rheumatoid arthritis patients. J autoimmunity. 2017;82:31\u201340. https:\/\/doi.org\/10.1016\/j.jaut.2017.04.007.","journal-title":"J autoimmunity"},{"key":"1029_CR11","doi-asserted-by":"publisher","first-page":"116357","DOI":"10.1016\/j.biopha.2024.116357","volume":"173","author":"L Mu\u00f1oz-Barrera","year":"2024","unstructured":"Mu\u00f1oz-Barrera L, Perez-Sanchez C, Ortega-Castro R, Corrales S, Luque-Tevar M, Cerd\u00f3 T, et al. Personalized cardiovascular risk assessment in rheumatoid arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs. Biomed Pharmacother. 2024;173:116357. https:\/\/doi.org\/10.1016\/j.biopha.2024.116357.","journal-title":"Biomed Pharmacother"},{"key":"1029_CR12","doi-asserted-by":"publisher","first-page":"152740","DOI":"10.1016\/j.semarthrit.2025.152740","volume":"73","author":"J Avouac","year":"2025","unstructured":"Avouac J, Kay J, Choy E. Personalised treatment of rheumatoid arthritis based on cytokine profiles and synovial tissue signatures: potentials and challenges. Semin Arthritis Rheumatism. 2025;73:152740. https:\/\/doi.org\/10.1016\/j.semarthrit.2025.152740.","journal-title":"Semin Arthritis Rheumatism"},{"issue":"4","key":"1029_CR13","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1093\/rheumatology\/keab521","volume":"61","author":"N Yoosuf","year":"2022","unstructured":"Yoosuf N, Maciejewski M, Ziemek D, Jelinsky SA, Folkersen L, M\u00fcller M, et al. Early prediction of clinical response to anti-TNF treatment using multi-omics and machine learning in rheumatoid arthritis. Rheumatology. 2022;61(4):1680\u201389. https:\/\/doi.org\/10.1093\/rheumatology\/keab521.","journal-title":"Rheumatology"},{"key":"1029_CR14","doi-asserted-by":"publisher","first-page":"1703209","DOI":"10.3389\/fimmu.2025.1703209","volume":"16","author":"F Lu","year":"2026","unstructured":"Lu F, Shao Y, Chen Q, Liu Q, Liu H, Liu Z, et al. Multi-omics identification of immune-related biomarkers predicting tofacitinib response in rheumatoid arthritis. Front Immunol. 2026;16:1703209. https:\/\/doi.org\/10.3389\/fimmu.2025.1703209.","journal-title":"Front Immunol"},{"issue":"1","key":"1029_CR15","doi-asserted-by":"publisher","first-page":"5374","DOI":"10.1038\/s41467-025-60987-9","volume":"16","author":"MJ Lewis","year":"2025","unstructured":"Lewis MJ, \u00c7ubuk C, Surace AEA, Sciacca E, Lau R, Goldmann K, et al. Deep molecular profiling of synovial biopsies in the STRAP trial identifies signatures predictive of treatment response to biologic therapies in rheumatoid arthritis. Nat Commun. 2025;16(1):5374. https:\/\/doi.org\/10.1038\/s41467-025-60987-9.","journal-title":"Nat Commun"},{"issue":"3","key":"1029_CR16","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1097\/BOR.0b013e32835fd8eb","volume":"25","author":"C Pitzalis","year":"2013","unstructured":"Pitzalis C, Kelly S, Humby F. New learnings on the pathophysiology of RA from synovial biopsies. Curr Opin Rheumatol. 2013;25(3):334\u201344. https:\/\/doi.org\/10.1097\/BOR.0b013e32835fd8eb.","journal-title":"Curr Opin Rheumatol"},{"issue":"7811","key":"1029_CR17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41586-020-2222-z","volume":"582","author":"K Wei","year":"2020","unstructured":"Wei K, Korsunsky I, Marshall JL, Gao A, Watts GFM, Major T, et al. Notch signalling drives synovial fibroblast identity and arthritis pathology. Nature. 2020;582(7811):259\u201364. https:\/\/doi.org\/10.1038\/s41586-020-2222-z.","journal-title":"Nature"},{"key":"1029_CR18","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.3389\/fimmu.2018.01510","volume":"9","author":"S Kubo","year":"2018","unstructured":"Kubo S, Nakayamada S, Sakata K, Kitanaga Y, Ma X, Lee S, et al. Janus kinase inhibitor baricitinib modulates human innate and adaptive immune system. Front Immunol. 2018;9:1510. https:\/\/doi.org\/10.3389\/fimmu.2018.01510.","journal-title":"Front Immunol"},{"issue":"7","key":"1029_CR19","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.3390\/jcm10071431","volume":"10","author":"A Reddig","year":"2021","unstructured":"Reddig A, Voss L, Guttek K, Roggenbuck D, Feist E, Reinhold D. Impact of different JAK inhibitors and methotrexate on lymphocyte proliferation and DNA damage. JCM. 2021;10(7):1431. https:\/\/doi.org\/10.3390\/jcm10071431.","journal-title":"JCM"},{"issue":"4","key":"1029_CR20","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1365-3083.2011.02503.x","volume":"73","author":"VM Dominical","year":"2011","unstructured":"Dominical VM, B\u00e9rtolo MB, Almeida CB, Garrido VT, Miguel LI, Costa FF, et al. Neutrophils of rheumatoid arthritis patients on anti-TNF-\u03b1 therapy and in disease remission present reduced adhesive functions in association with decreased circulating neutrophil-attractant chemokine levels. Scand J Immunol. 2011;73(4):309\u201318. https:\/\/doi.org\/10.1111\/j.1365-3083.2011.02503.x.","journal-title":"Scand J Immunol"},{"key":"1029_CR21","doi-asserted-by":"publisher","unstructured":"Oberoi R, Schuett J, Schuett H, Koch A-K, Luchtefeld M, Grote K, et al. Targeting tumor necrosis Factor-\u03b1 with Adalimumab: effects on endothelial activation and monocyte adhesion. In: Hagemeyer CE, editor. PLoS ONE. Vol. 11. 2016. p. e0160145. https:\/\/doi.org\/10.1371\/journal.pone.0160145.","DOI":"10.1371\/journal.pone.0160145"},{"issue":"7","key":"1029_CR22","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1002\/eji.201243178","volume":"43","author":"G P\u00e9rez-Rivero","year":"2013","unstructured":"P\u00e9rez-Rivero G, Cascio G, Soriano SF, Sanz \u00c1G, De Guinoa JS, Rodr\u00edguez-Frade JM, et al. Janus kinases 1 and 2 regulate chemokine-mediated integrin activation and na\u00efve T-cell homing. Eur J Immunol. 2013;43(7):1745\u201357. https:\/\/doi.org\/10.1002\/eji.201243178.","journal-title":"Eur J Immunol"},{"issue":"8","key":"1029_CR23","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s00296-009-1089-y","volume":"30","author":"HM Choi","year":"2010","unstructured":"Choi HM, Oh DH, Bang JS, Yang H-I, Yoo MC, Kim KS. Differential effect of IL-1\u03b2 and TNF-\u03b1 on the production of IL-6, IL-8 and PGE2 in fibroblast-like synoviocytes and THP-1 macrophages. Rheumatol Int. 2010;30(8):1025\u201333. https:\/\/doi.org\/10.1007\/s00296-009-1089-y.","journal-title":"Rheumatol Int"},{"key":"1029_CR24","doi-asserted-by":"publisher","first-page":"120516","DOI":"10.1016\/j.lfs.2022.120516","volume":"298","author":"S Srivastava","year":"2022","unstructured":"Srivastava S, Rasool M. Underpinning IL-6 biology and emphasizing selective JAK blockade as the potential alternate therapeutic intervention for rheumatoid arthritis. Life Sci. 2022;298:120516. https:\/\/doi.org\/10.1016\/j.lfs.2022.120516.","journal-title":"Life Sci"},{"key":"1029_CR25","doi-asserted-by":"publisher","unstructured":"Chen D-Y, Chen Y-M, Chen H-H, Hsieh C-W, Lin C-C, Lan J-L. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-\u03b1 therapy. Arthritis Res Ther. 2011;13(4):R126. https:\/\/doi.org\/10.1186\/ar3431.","DOI":"10.1186\/ar3431"},{"key":"1029_CR26","doi-asserted-by":"publisher","first-page":"106748","DOI":"10.1016\/j.intimp.2020.106748","volume":"86","author":"M d\u2019Alessandro M","year":"2020","unstructured":"d\u2019Alessandro M M, Perillo F, Metella Refini R, Bergantini L, Bellisai F, Selvi E, et al. Efficacy of baricitinib in treating rheumatoid arthritis: modulatory effects on fibrotic and inflammatory biomarkers in a real-life setting. Int Immunopharmacol. 2020;86:106748. https:\/\/doi.org\/10.1016\/j.intimp.2020.106748.","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"1029_CR27","doi-asserted-by":"publisher","first-page":"15645","DOI":"10.1038\/s41598-018-34026-1","volume":"8","author":"A Hammitzsch","year":"2018","unstructured":"Hammitzsch A, Chen L, De Wit J, Al-Mossawi MH, Ridley A, Sekine T, et al. Inhibiting ex-vivo Th17 responses in ankylosing spondylitis by targeting Janus kinases. Sci Rep. 2018;8(1):15645. https:\/\/doi.org\/10.1038\/s41598-018-34026-1.","journal-title":"Sci Rep"},{"issue":"1","key":"1029_CR28","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s12079-022-00686-y","volume":"17","author":"DAB Rex","year":"2023","unstructured":"Rex DAB, Dagamajalu S, Gouda MM, Suchitha GP, Chanderasekaran J, Raju R, et al. A comprehensive network map of IL-17A signaling pathway. J Cell Commun Signal. 2023;17(1):209\u201315. https:\/\/doi.org\/10.1007\/s12079-022-00686-y.","journal-title":"J Cell Commun Signal"},{"key":"1029_CR29","doi-asserted-by":"publisher","unstructured":"Bughani U, Saha A, Kuriakose A, Nair R, Sadashivarao RB, Venkataraman R, et al. T cell activation and differentiation is modulated by a CD6 domain 1 antibody itolizumab. In: J VDV, editor. PLoS ONE. Vol. 12. 2017. p. e0180088. https:\/\/doi.org\/10.1371\/journal.pone.0180088.","DOI":"10.1371\/journal.pone.0180088"},{"issue":"12","key":"1029_CR30","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.3390\/cells9122589","volume":"9","author":"M Velasco-de Andr\u00e9s","year":"2020","unstructured":"Velasco-de Andr\u00e9s M, Casad\u00f3-Llombart S, Catal\u00e0 C, Leyton-Pereira A, Lozano F, Aranda F. Soluble CD5 and CD6: lymphocytic class I scavenger receptors as immunotherapeutic agents. Cells. 2020;9(12):2589. https:\/\/doi.org\/10.3390\/cells9122589.","journal-title":"Cells"},{"issue":"2","key":"1029_CR31","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1111\/j.1365-2567.2004.02004.x","volume":"114","author":"W Kim","year":"2005","unstructured":"Kim W, Kang Y, Koh E, Ahn K, Cha H, Lee W. LIGHT is involved in the pathogenesis of rheumatoid arthritis by inducing the expression of pro-inflammatory cytokines and MMP-9 in macrophages. Immunology. 2005;114(2):272\u201379. https:\/\/doi.org\/10.1111\/j.1365-2567.2004.02004.x.","journal-title":"Immunology"},{"issue":"9","key":"1029_CR32","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1136\/annrheumdis-2022-222335","volume":"81","author":"T D\u00f6rner","year":"2022","unstructured":"D\u00f6rner T, Tanaka Y, Dow ER, Koch AE, Silk M, Ross Terres JA, et al. Mechanism of action of baricitinib and identification of biomarkers and key immune pathways in patients with active systemic lupus erythematosus. Ann Rheumatic Dis. 2022;81(9):1267\u201372. https:\/\/doi.org\/10.1136\/annrheumdis-2022-222335.","journal-title":"Ann Rheumatic Dis"},{"key":"1029_CR33","doi-asserted-by":"publisher","first-page":"1100869","DOI":"10.3389\/fimmu.2023.1100869","volume":"14","author":"MA Murayama","year":"2023","unstructured":"Murayama MA, Shimizu J, Miyabe C, Yudo K, Miyabe Y. Chemokines and chemokine receptors as promising targets in rheumatoid arthritis. Front Immunol. 2023;14:1100869. https:\/\/doi.org\/10.3389\/fimmu.2023.1100869.","journal-title":"Front Immunol"},{"issue":"6","key":"1029_CR34","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.3390\/jcm13061821","volume":"13","author":"M Benucci","year":"2024","unstructured":"Benucci M, Li Gobbi F, Damiani A, Russo E, Guiducci S, Manfredi M, et al. Real-Life comparison of four JAK inhibitors in rheumatoid arthritis (ELECTRA-i study). JCM. 2024;13(6):1821. https:\/\/doi.org\/10.3390\/jcm13061821.","journal-title":"JCM"},{"issue":"1","key":"1029_CR35","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41467-022-35264-8","volume":"14","author":"J-S Moon","year":"2023","unstructured":"Moon J-S, Younis S, Ramadoss NS, Iyer R, Sheth K, Sharpe O, et al. Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis. Nat Commun. 2023;14(1):319. https:\/\/doi.org\/10.1038\/s41467-022-35264-8.","journal-title":"Nat Commun"},{"issue":"12","key":"1029_CR36","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nrd.2017.201","volume":"16","author":"DM Schwartz","year":"2017","unstructured":"Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O\u2019shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843\u201362. https:\/\/doi.org\/10.1038\/nrd.2017.201.","journal-title":"Nat Rev Drug Discov"},{"key":"1029_CR37","doi-asserted-by":"publisher","first-page":"1026521","DOI":"10.3389\/fmed.2022.1026521","volume":"9","author":"M Gurrea-Rubio","year":"2022","unstructured":"Gurrea-Rubio M, Fox DA. The dual role of CD6 as a therapeutic target in cancer and autoimmune disease. Front Med. 2022;9:1026521. https:\/\/doi.org\/10.3389\/fmed.2022.1026521.","journal-title":"Front Med"},{"issue":"5","key":"1029_CR38","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1007\/s10753-013-9639-6","volume":"36","author":"G Slobodin","year":"2013","unstructured":"Slobodin G, Kaly L, Peri R, Kessel A, Rosner I, Toubi E, et al. Higher expression of latency-associated peptide on the surface of peripheral blood monocytes in patients with rheumatoid arthritis may be protective against articular erosions. Inflammation. 2013;36(5):1075\u201378. https:\/\/doi.org\/10.1007\/s10753-013-9639-6.","journal-title":"Inflammation"},{"issue":"8","key":"1029_CR39","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.4049\/jimmunol.1600399","volume":"197","author":"X Liu","year":"2016","unstructured":"Liu X, Zhou H, Huang X, Cui J, Long T, Xu Y, et al. A broad blockade of signaling from the IL-20 family of cytokines potently attenuates collagen-induced arthritis. J Immunol. 2016;197(8):3029\u201337. https:\/\/doi.org\/10.4049\/jimmunol.1600399.","journal-title":"J Immunol"},{"issue":"11","key":"1029_CR40","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1136\/ard.61.11.975","volume":"61","author":"TCA Tolboom","year":"2002","unstructured":"Tolboom TCA, Pieterman E, Van Der Laan WH, Toes REM, Huidekoper AL, Nelissen RGHH, et al. Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10. Ann Rheumatic Dis. 2002;61(11):975\u201380. https:\/\/doi.org\/10.1136\/ard.61.11.975.","journal-title":"Ann Rheumatic Dis"},{"issue":"2","key":"1029_CR41","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.jbspin.2018.05.006","volume":"86","author":"MVC Nguyen","year":"2019","unstructured":"Nguyen MVC, Baillet A, Romand X, Trocm\u00e9 C, Courtier A, Marotte H, et al. Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis. Joint Bone Spine. 2019;86(2):195\u2013201. https:\/\/doi.org\/10.1016\/j.jbspin.2018.05.006.","journal-title":"Joint Bone Spine"},{"key":"1029_CR42","doi-asserted-by":"publisher","unstructured":"Wang G, Van Driel BJ, Liao G, O\u2019keeffe MS, Halibozek PJ, Flipse J, et al. Migration of myeloid cells during inflammation is differentially regulated by the cell surface receptors Slamf1 and Slamf8. In: Satoskar AR, editor. PLoS ONE. Vol. 10. 2015. p. e0121968. https:\/\/doi.org\/10.1371\/journal.pone.0121968.","DOI":"10.1371\/journal.pone.0121968"},{"issue":"8657","key":"1029_CR43","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/S0140-6736(89)90430-3","volume":"334","author":"F Brennan","year":"1989","unstructured":"Brennan F. Inhibitory effect of TNF alpha; antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet. 1989;334(8657):244\u201347. https:\/\/doi.org\/10.1016\/S0140-6736(89)90430-3.","journal-title":"Lancet"},{"key":"1029_CR44","doi-asserted-by":"publisher","unstructured":"Rendas-Baum R, Wallenstein GV, Koncz T, Kosinski M, Yang M, Bradley J, et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-\u03b1 inhibitors. Arthritis Res Ther. 2011;13(1):R25. https:\/\/doi.org\/10.1186\/ar3249.","DOI":"10.1186\/ar3249"},{"issue":"5","key":"1029_CR45","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/nrrheum.2015.8","volume":"11","author":"JS Smolen","year":"2015","unstructured":"Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol. 2015;11(5):276\u201389. https:\/\/doi.org\/10.1038\/nrrheum.2015.8.","journal-title":"Nat Rev Rheumatol"},{"key":"1029_CR46","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.clim.2017.07.019","volume":"186","author":"T Takeuchi","year":"2018","unstructured":"Takeuchi T. Biomarkers as a treatment guide in rheumatoid arthritis. Clin Immunol. 2018;186:59\u201362. https:\/\/doi.org\/10.1016\/j.clim.2017.07.019.","journal-title":"Clin Immunol"},{"key":"1029_CR47","doi-asserted-by":"publisher","first-page":"1409555","DOI":"10.3389\/fimmu.2024.1409555","volume":"15","author":"Y Shi","year":"2024","unstructured":"Shi Y, Zhou M, Chang C, Jiang P, Wei K, Zhao J, et al. Advancing precision rheumatology: applications of machine learning for rheumatoid arthritis management. Front Immunol. 2024;15:1409555. https:\/\/doi.org\/10.3389\/fimmu.2024.1409555.","journal-title":"Front Immunol"},{"key":"1029_CR48","doi-asserted-by":"publisher","unstructured":"Chen S-F, Wu T-S, Chang K-Y, Lo S-M, Chen Y-T, Kao C-M, et al. Integrative proteomic and machine learning strategies identify key biomarkers associated with response to JAK inhibitor in rheumatoid arthritis. Arthritis Res Ther. 2026. https:\/\/doi.org\/10.1186\/s13075-026-03880-0.","DOI":"10.1186\/s13075-026-03880-0"},{"key":"1029_CR49","doi-asserted-by":"publisher","unstructured":"Vogel A, Martin K, Soukup K, Halfmann A, Kerndl M, Brunner JS, et al. JAK1 signaling in dendritic cells promotes peripheral tolerance in autoimmunity through PD-L1-mediated regulatory T cell induction. Cell reports. 2022;38:110420. https:\/\/doi.org\/10.1016\/j.celrep.2022.110420.","DOI":"10.1016\/j.celrep.2022.110420"},{"key":"1029_CR50","doi-asserted-by":"publisher","unstructured":"Enyindah-Asonye G, Li Y, Ruth JH, Spassov DS, Hebron KE, Zijlstra A, et al. CD318 is a ligand for CD6. Proc Natl Acad Sci USA [Internet]. 2017 [cited 2025 Aug 12]; 114(33). https:\/\/doi.org\/10.1073\/pnas.1704008114.","DOI":"10.1073\/pnas.1704008114"},{"key":"1029_CR51","doi-asserted-by":"publisher","first-page":"108875","DOI":"10.1016\/j.biopha.2019.108875","volume":"115","author":"K Chen","year":"2019","unstructured":"Chen K, Lin Z-W, He S, Wang C, Yang J, Lu Y, et al. Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR\/PI3K\/AKT\/m-TOR pathway. Biomed Pharmacother. 2019;115:108875. https:\/\/doi.org\/10.1016\/j.biopha.2019.108875.","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"1029_CR52","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.cyto.2007.10.004","volume":"41","author":"TW Kragstrup","year":"2008","unstructured":"Kragstrup TW, Otkjaer K, Holm C, J\u00f8rgensen A, Hokland M, Iversen L, et al. The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy. Cytokine. 2008;41(1):16\u201323. https:\/\/doi.org\/10.1016\/j.cyto.2007.10.004.","journal-title":"Cytokine"},{"key":"1029_CR53","doi-asserted-by":"publisher","unstructured":"Vu YH, Furue M, Tsuji G. The role of interleukin-24 in atopic dermatitis. Explor Immunol [Internet]. 2021 [cited 2025 Sept 3]; https:\/\/doi.org\/10.37349\/ei.2021.00002.","DOI":"10.37349\/ei.2021.00002"},{"key":"1029_CR54","doi-asserted-by":"publisher","unstructured":"Barthel C, Yeremenko N, Jacobs R, Schmidt RE, Bernateck M, Zeidler H, et al. Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis. Arthritis Res Ther. 2009;11(3):R82. https:\/\/doi.org\/10.1186\/ar2716.","DOI":"10.1186\/ar2716"},{"issue":"10","key":"1029_CR55","doi-asserted-by":"publisher","first-page":"7128","DOI":"10.4049\/jimmunol.179.10.7128","volume":"179","author":"Y Yamaguchi","year":"2007","unstructured":"Yamaguchi Y, Fujio K, Shoda H, Okamoto A, Tsuno NH, Takahashi K, et al. IL-17B and IL-17C are associated with TNF-\u03b1 production and contribute to the exacerbation of inflammatory arthritis. J Immunol. 2007;179(10):7128\u201336. https:\/\/doi.org\/10.4049\/jimmunol.179.10.7128.","journal-title":"J Immunol"},{"key":"1029_CR56","doi-asserted-by":"publisher","unstructured":"Prasad B, McGeough C, Eakin A, Ahmed T, Small D, Gardiner P, et al. Atrpred: a machine learning based tool for clinical decision making of anti-TNF treatment in rheumatoid arthritis patients. In: Schlessinger A, editor. PLoS Comput Biol. Vol. 18. 2022. p. e1010204. https:\/\/doi.org\/10.1371\/journal.pcbi.1010204.","DOI":"10.1371\/journal.pcbi.1010204"},{"key":"1029_CR57","doi-asserted-by":"publisher","unstructured":"Agueusop I, Margerie D, Remaury A, Brard R, Frau F, Gerard E, et al. Deciphering differential biomarkers for anti-interleukin-6 receptor and anti-tumour necrosis factor-\u03b1 treatment response in rheumatoid arthritis by multiomics analysis. RMD Open. 2025;11(3):e005556. https:\/\/doi.org\/10.1136\/rmdopen-2025-005556.","DOI":"10.1136\/rmdopen-2025-005556"},{"issue":"10","key":"1029_CR58","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1093\/rheumatology\/kev241","volume":"54","author":"MR Hillen","year":"2015","unstructured":"Hillen MR, Radstake TRDJ, Hack CE, Van Roon JAG. Thymic stromal lymphopoietin as a novel mediator amplifying immunopathology in rheumatic disease: fig. 1. Rheumatology. 2015;54(10):1771\u201379. https:\/\/doi.org\/10.1093\/rheumatology\/kev241.","journal-title":"Rheumatology"},{"key":"1029_CR59","doi-asserted-by":"publisher","first-page":"1358750","DOI":"10.3389\/fonc.2024.1358750","volume":"14","author":"L Yi","year":"2024","unstructured":"Yi L, Gai Y, Chen Z, Tian K, Liu P, Liang H, et al. Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights. Front Oncol. 2024;14:1358750. https:\/\/doi.org\/10.3389\/fonc.2024.1358750.","journal-title":"Front Oncol"},{"key":"1029_CR60","doi-asserted-by":"publisher","unstructured":"Ptacek J, Hawtin RE, Sun D, Louie B, Evensen E, Mittleman BB, et al. Diminished cytokine-induced Jak\/STAT signaling is associated with rheumatoid arthritis and disease activity. In: Srivastava A, editor. PLoS ONE. Vol. 16. 2021. p. e0244187. https:\/\/doi.org\/10.1371\/journal.pone.0244187.","DOI":"10.1371\/journal.pone.0244187"},{"issue":"4","key":"1029_CR61","doi-asserted-by":"publisher","first-page":"260","DOI":"10.3109\/03009742.2012.754937","volume":"42","author":"C Eriksson","year":"2013","unstructured":"Eriksson C, Rantap\u00e4\u00e4-Dahlqvist S, Sundqvist K. Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor infliximab in patients with rheumatoid arthritis. Scand J Rheumatol. 2013;42(4):260\u201365. https:\/\/doi.org\/10.3109\/03009742.2012.754937.","journal-title":"Scand J Rheumatol"},{"issue":"9","key":"1029_CR62","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.5455\/annalsmedres.2019.05.251","volume":"26","author":"A Bulur","year":"2019","unstructured":"Bulur A, Erden A, Inanc N. Evaluation of relationship between cytokine and chemokine levels measured by using multiplex laboratory method before and after treatment and clinical course and treatment response in rheumathoid arthritis patients receiving TNF- and #945; blocker therapy. Ann Med Res. 2019;26(9):2053. https:\/\/doi.org\/10.5455\/annalsmedres.2019.05.251.","journal-title":"Ann Med Res"},{"key":"1029_CR63","doi-asserted-by":"publisher","first-page":"43","DOI":"10.2147\/ITT.S243636","volume":"9","author":"NM Elemam","year":"2020","unstructured":"Elemam NM, Hannawi S, Maghazachi AA. Role of chemokines and chemokine receptors in rheumatoid arthritis. ITT. 2020, Volume, 9: 43\u201356. https:\/\/doi.org\/10.2147\/ITT.S243636.","journal-title":"ITT"},{"issue":"3","key":"1029_CR64","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41423-026-01386-y","volume":"23","author":"FS Shaikh","year":"2026","unstructured":"Shaikh FS, Shanta MA, Singh AK, Daniels AM, Khuder SA, Thiele GM, et al. TWEAK receptor (Fn14) exacerbates TNF-\u03b1-induced inflammation in rheumatoid arthritis synovial fibroblasts and influences response to anti-TNF-\u03b1 therapy. Cell Mol Immunol [Internet]. 2026;23(3):315\u201328. https:\/\/doi.org\/10.1038\/s41423-026-01386-y.","journal-title":"Cell Mol Immunol"},{"issue":"1","key":"1029_CR65","doi-asserted-by":"publisher","first-page":"18","DOI":"10.14573\/altex.1804161","volume":"36","author":"M Broeren","year":"2019","unstructured":"Broeren M. A three-dimensional model to study human synovial pathology. ALTEX. 2019;36(1):18\u201328. https:\/\/doi.org\/10.14573\/altex.1804161.","journal-title":"ALTEX"},{"issue":"10","key":"1029_CR66","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1007\/s00296-013-2743-y","volume":"33","author":"S Hirohata","year":"2013","unstructured":"Hirohata S, Tomita T, Yoshikawa H, Kyogoku M. TNF inhibitors induce discoid fibrosis in the sublining layers of the synovium with degeneration of synoviocytes in rheumatoid arthritis. Rheumatol Int. 2013;33(10):2473\u201381. https:\/\/doi.org\/10.1007\/s00296-013-2743-y.","journal-title":"Rheumatol Int"}],"container-title":["Biomarker Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-026-01029-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40364-026-01029-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-026-01029-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:16:30Z","timestamp":1792631790000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40364-026-01029-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1029"],"URL":"https:\/\/doi.org\/10.1186\/s40364-026-01029-4","relation":{},"ISSN":["2050-7771"],"issn-type":[{"value":"2050-7771","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"19 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the Research Ethics Committee of Reina Sofia Hospital in C\u00f3rdoba (CEIm Provincial de C\u00f3rdoba), accredited under Decree 8\/2020 of the Regional Government of Andalusia, Spain. The approval was granted on June 26, 2025, at session number 374, with committee reference number 6225 (application code: SICEIA-2025-001754; study code: PI24\/00959). The study was conducted in accordance with the Spanish Biomedical Research Law 14\/2007, Royal Legislative Decree 1\/2015, and Organic Law 3\/2018 on Personal Data Protection. Written informed consent was obtained from all patients prior to their inclusion in the study, in accordance with the approved informed consent forms (version 1, dated June 2, 2025).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"146"}}