{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:37:52Z","timestamp":1792643872309,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Aquaporin\u20104\u2010IgG seropositive neuromyelitis optica spectrum disorder (AQP4+ NMOSD), myelin oligodendrocyte glycoprotein antibody\u2010associated disease (MOGAD), and multiple sclerosis (MS) are pathophysiologically distinct neuroinflammatory disorders. Complement activation is a major mechanism of injury in AQP4+ NMOSD, whereas its role in MS is complex and in MOGAD controversial. We aimed to compare complement components and cytokines between AQP4+ NMOSD, MOGAD, and MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CSF complement components, CSF and plasma cytokines, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured in people with AQP4+ NMOSD (CSF:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919; plasma:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918), MOGAD (CSF:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929; plasma:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200935) and MS (CSF:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936; plasma:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200958) with recent disease activity. Controls included subjects with non\u2010inflammatory conditions (CSF:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200951) and healthy controls (plasma:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CSF IL\u201010 and TNF\u2010a were elevated across all neuroinflammatory disease groups relative to controls. CSF IL\u20106 was elevated only in AQP4+ NMOSD and MOGAD. There were no significant differences in plasma cytokines between groups. Most complement components were elevated in AQP4+\u2009NMOSD and MOGAD; only specific activation products (C2b, C3d, C4a, C5a) were elevated in MS. CSF GFAP and NfL correlated with several CSF cytokines and complement components in AQP4+ NMOSD and MOGAD. Expanded Disability Status Scale at nadir during attacks correlated with CSF BAFF, GFAP, free C1q, C1s, C1s\u2010C1inh, C4a in AQP4+ NMOSD, and CSF IL\u201010, TNF\u2010a, free C1q, C1inh, C4a in MOGAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our findings suggest distinct CSF cytokine profiles in AQP4+ NMOSD, MOGAD, and MS, and widespread activation of complement pathways in AQP4+ NMOSD and MOGAD. CSF complement and cytokine profiling may help characterize neuroinflammatory disease mechanisms, although further validation of these findings in larger cohorts is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70549","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:45:33Z","timestamp":1792640733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Complement Activation and Cytokine Signatures in\n                    <scp>AQP4<\/scp>\n                    +\n                    <scp>NMOSD<\/scp>\n                    ,\n                    <scp>MOGAD<\/scp>\n                    , and\n                    <scp>MS<\/scp>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0419-233X","authenticated-orcid":false,"given":"Angeliki G.","family":"Filippatou","sequence":"first","affiliation":[{"name":"Department of 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