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Centre"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Objectives:<\/jats:title>\n                    <jats:p>This cohort study aimed to identify blood-based biomarkers associated with progression independent of relapse activity (PIRA) in persons with multiple sclerosis (pwMS) using the multiplex NUcleic Acid-Linked Immuno-Sandwich Assay (NULISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      NULISA \u2018CNS Disease Panel\u2019 and \u2018Inflammation Panel\u2019 were applied on plasma samples from pwMS following B cell-depleting therapy (BCDT;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009185) or fingolimod (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009200), median follow-up 4.0 (BCDT) and 9.1 (fingolimod) years. Plasma NULISA results (322 unique proteins; 0.9 and 1\u2009year after treatment start, respectively) were investigated for their potential to prognosticate PIRA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      \u2018CNS Disease Panel\u2019 derived glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified as predictive of PIRA by multivariable Cox regression models (GFAP: BCDT: hazard ratio (HR) = 1.79, 95% confidence interval (CI) = 1.26\u20132.55,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0011; fingolimod: HR = 1.73, 95% CI = 1.14\u20132.64,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0104; NfL: BCDT: HR = 1.99, 95% CI = 1.31\u20133.02,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0013). GFAP derived from the \u2018Inflammation Panel\u2019 exhibited patterns like those observed with \u2018CNS Disease Panel\u2019 derived GFAP. Beyond GFAP and NfL, 12 biomarker candidates predictive of PIRA were identified. No target passed multiple test corrections, but GFAP consistently showed the highest hazard.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Among over 300 proteins investigated by NULISA, GFAP was the main biomarker significantly associated with future PIRA risk in our cohort.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251375780","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T12:36:09Z","timestamp":1760445369000},"page":"1531-1542","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Biomarker discovery using NUcleic Acid-Linked Immuno-Sandwich Assay in multiple sclerosis patients experiencing progression independent of relapse activity"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6206-3339","authenticated-orcid":false,"given":"Sofia","family":"Sandgren","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Neurology, Sahlgrenska University Hospital, Region V\u00e4stra G\u00f6taland, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra Maleska","family":"Maceski","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-8174","authenticated-orcid":false,"given":"Pascal","family":"Benkert","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0786-2872","authenticated-orcid":false,"given":"Maximilian","family":"Einsiedler","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Schaedelin","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Oechtering","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Achtnichts","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice H","family":"Lalive","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Division of Neurology, and Department of Medicine, Translational Biomarker Group, Geneva, Switzerland; Division of Laboratory Medicine, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Teaching and Research Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-3129","authenticated-orcid":false,"given":"Caroline","family":"Pot","sequence":"additional","affiliation":[{"name":"Service of Neurology and Laboratories of Neuroimmunology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, London, UK; 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Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-8761","authenticated-orcid":false,"given":"Cristina","family":"Granziera","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland; Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9731-4169","authenticated-orcid":false,"given":"Ahmed","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leppert","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; 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Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6963-8892","authenticated-orcid":false,"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; Department of Neurology, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3331"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1568"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27034"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.5250"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27096"},{"key":"e_1_3_3_7_2","article-title":"GFAP and NfL as predictors of disease progression and relapses in fingolimod treated MS patients","author":"Maleska AM","unstructured":"Maleska AM, Benkert P, Einsiedler M et al. 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