{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:13:39Z","timestamp":1787318019369,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003000","name":"Stichting MS Research","doi-asserted-by":"publisher","award":["MS14\u2010888"],"award-info":[{"award-number":["MS14\u2010888"]}],"id":[{"id":"10.13039\/501100003000","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Relapsing\u2013remitting (RR) and primary progressive (PP) multiple sclerosis (MS) have distinct clinical courses, but underlying pathophysiological differences remain unclear. We compared pathological components between RRMS, PPMS, and other inflammatory and neurodegenerative disorders, leveraging soluble biomarkers and post\u2010mortem pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum and cerebrospinal fluid (CSF) of people diagnosed with (pw) PPMS (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009104), RRMS (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938), Alzheimer's disease (AD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922), neuromyelitis optica spectrum disorder (NMOSD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910), and myelin oligodendrocyte glycoprotein\u2013associated disease (MOGAD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) were collected. B\u2010cell maturation antigen (BCMA), soluble CD27 (sCD27), osteopontin (OPN), chitinase\u20103\u2010like\u20101 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and synaptosomal\u2010associated protein\u201025 (SNAP25) were measured. Lymphocytes (CD20\n                      <jats:sup>+<\/jats:sup>\n                      , CD138\n                      <jats:sup>+<\/jats:sup>\n                      , CD3\n                      <jats:sup>+<\/jats:sup>\n                      ) and pyramidal\u2010tract axonal density in RR\u2010onset (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200986) and PPMS (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200945) post\u2010mortem brain tissue were quantified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Soluble and post\u2010mortem tissue biomarkers did not differ between pwRRMS and pwPPMS. Compared to AD, MS had higher CSF sCD27 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) but lower serum CHI3L1 and GFAP, and CSF OPN and SNAP25 (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Serum OPN was lower in RRMS than NMOSD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013). Principal component analyses and K\u2010means clustering showed substantial overlap of RRMS and PPMS biomarkers, distinct from AD. In all pwMS, serum NfL and CSF BCMA correlated with clinical\/radiological disease activity, CSF BCMA and sCD27 with inflammatory parameters, and serum GFAP, CSF GFAP, and CSF NfL with Expanded Disability Status Scale (EDSS) score.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum and CSF soluble biomarker profiles and post\u2010mortem pathology do not differentiate RRMS from PPMS diagnoses but reflect the extent of inflammation and tissue damage. Detailed assessment of MS\u2010associated inflammation and tissue damage may enhance classification and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70052","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T06:42:27Z","timestamp":1738737747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multifaceted Biomarkers Suggest a Similar Profile of\n                    <scp>CNS<\/scp>\n                    Pathology in Relapsing and Progressive\n                    <scp>MS<\/scp>"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-5023","authenticated-orcid":false,"given":"Katelijn M.","family":"Blok","sequence":"first","affiliation":[{"name":"Department of Neurology, MS Center ErasMS Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Department of Neurology Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3460-9948","authenticated-orcid":false,"given":"Romy A. M.","family":"Klein Kranenbarg","sequence":"additional","affiliation":[{"name":"Department of Neurology, MS Center ErasMS Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Department of Neurology Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirtana","family":"Ananth","sequence":"additional","affiliation":[{"name":"Division of Neuroinflammation and Glial Biology, Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J.","family":"Engelenburg","sequence":"additional","affiliation":[{"name":"Neuroimmunology Researchgroup Netherlands Institute for Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aletta","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Neuroimmunology Researchgroup Netherlands Institute for Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia A. A.","family":"Giannini","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Center Rotterdam Erasmus MC , University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"de Beukelaar","sequence":"additional","affiliation":[{"name":"Department of Neurology Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harro","family":"Seelaar","sequence":"additional","affiliation":[{"name":"Department of Neurology and Alzheimer Center Rotterdam Erasmus MC , University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Huitinga","sequence":"additional","affiliation":[{"name":"Neuroimmunology Researchgroup Netherlands Institute for Neuroscience  Amsterdam The 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