{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:30:18Z","timestamp":1790278218207,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009009","name":"Novartis Pharmaceuticals Canada","doi-asserted-by":"publisher","award":["CAPCR ID#20\u20105095"],"award-info":[{"award-number":["CAPCR ID#20\u20105095"]}],"id":[{"id":"10.13039\/100009009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000142","name":"Arthritis Society","doi-asserted-by":"publisher","award":["22\u20100000000135"],"award-info":[{"award-number":["22\u20100000000135"]}],"id":[{"id":"10.13039\/501100000142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive interleukin (IL)\u201017A\u2013producing cells are implicated in a central role. Therapeutically, biologics that target IL\u201017A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some patients with axSpA do not respond to IL\u201017A\u2013blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC\u2010R) and nonresponders (SEC\u2010NR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells were collected from 30 patients with axSpA before and 24 weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC\u2010R and SEC\u2010NR using flow cytometry. Mature CD45RO+CD45RA\u2010CD4+ T cells were fluorescent\u2010activated cell sorting sorted, and RNA was measured using NanoString analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SEC\u2010NR had an increased frequency of IL\u201017A\u2013producing ROR\u03b3t+CD4+ T cells compared to healthy controls before secukinumab treatment (<jats:italic>P<\/jats:italic> &lt; 0.01). SEC\u2010NR had a significant increase of CXCR3+ CD4+ T cells before secukinumab treatment compared to SEC\u2010R (<jats:italic>P<\/jats:italic> &lt; 0.01). Differentially expressed gene analysis revealed up\u2010regulation of type 1 interferon (IFN)\u2010regulated genes in SEC\u2010NR patients compared to SEC\u2010R patients after receiving the biologic. SEC\u2010R patients had an up\u2010regulated cytotoxic CD4+ T cell gene signature before receiving secukinumab treatment compared to SEC\u2010NR patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The increased frequency of IL\u201017A\u2013producing cells in SEC\u2010NR patients suggests a larger inflammatory burden than SEC\u2010R patients. With treatment, SEC\u2010NR patients have a more pronounced type 1 IFN signature than SEC\u2010R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42974-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42974","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:33:40Z","timestamp":1724114020000},"page":"34-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhanced Type 1 Interferon Signature in Axial Spondyloarthritis Patients Unresponsive to Secukinumab Treatment"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-2775","authenticated-orcid":false,"given":"Addison","family":"Pacheco","sequence":"first","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network and University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinead","family":"Maguire","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network and Toronto Western Hospital, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoya","family":"Qaiyum","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tang","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Bridger","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Lim","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fataneh","family":"Tavasolian","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enoch","family":"Yau","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah 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