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Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      ) NMOSD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG\n                      <jats:sup>+<\/jats:sup>\n                      ) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      patients over a median observation period of 4.25 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In patients with AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      NMOSD, median sGFAP (109.2 pg\/ml) was non-significantly higher than in MOG-IgG\n                      <jats:sup>+<\/jats:sup>\n                      patients (81.1 pg\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.83) and healthy controls (67.7 pg\/ml;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      , but not MOG-IgG\n                      <jats:sup>+<\/jats:sup>\n                      patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = \u2212\u20091.28,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.01). While in AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      , but not MOG-IgG\n                      <jats:sup>+<\/jats:sup>\n                      patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.15) and MSFC (standardized effect size = \u2212\u20091.75,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.06) in patients with AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      NMOSD. Patients with AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      NMOSD with sGFAP &gt;\u200990 pg\/ml at baseline had a shorter time to a future attack than those with sGFAP \u2264\u200990 pg\/ml (adjusted hazard ratio [95% confidence interval] = 11.6 [1.3\u2013105.6],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.03). In contrast, baseline sNfL levels above the 75\n                      <jats:sup>th<\/jats:sup>\n                      age adjusted percentile were not associated with a shorter time to a future attack in patients with AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      NMOSD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest a potential role for sGFAP as biomarker for disease severity and future disease activity in patients with AQP4-IgG\n                      <jats:sup>+<\/jats:sup>\n                      NMOSD in phases of clinical remission.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-021-02138-7","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T08:19:39Z","timestamp":1620029979000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder"],"prefix":"10.1186","volume":"18","author":[{"given":"Patrick","family":"Schindler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Grittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Oechtering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leppert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Siebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankelien S.","family":"Duchow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederike C.","family":"Oertel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Asseyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kuchling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna G.","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander U.","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Benkert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Reindl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Jarius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedemann","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Bellmann-Strobl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1962-6014","authenticated-orcid":false,"given":"Klemens","family":"Ruprecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"issue":"2","key":"2138_CR1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/cei.12271","volume":"176","author":"S Jarius","year":"2014","unstructured":"Jarius S, Wildemann B, Paul F. 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Ann Clin Transl Neurol. 2020;7(12):2508\u201323. https:\/\/doi.org\/10.1002\/acn3.51234.","journal-title":"Ann Clin Transl Neurol"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-021-02138-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-021-02138-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-021-02138-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T17:05:41Z","timestamp":1626800741000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-021-02138-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2138"],"URL":"https:\/\/doi.org\/10.1186\/s12974-021-02138-7","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,1]]},"assertion":[{"value":"22 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the institutional review board, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin (EA1\/131\/09 and EA1\/182\/10) and all participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PS reports no disclosures.UG reports no disclosures.JO has received travel grants from Novartis, Biogen and Bayer.DL has been a Novartis employee until 2019\/1.NS reports no disclosures.ASD reports no disclosures.FCO was employed by Nocturne, unrelated to this project.SA received a conference grant from Celgene and speaking fees from Bayer healthcare and Roche, unrelated to this project.JK reports no disclosures.HGZ received research grants from Novartis and speaking fees from Bayer Healthcare, unrelated to this project.AUB is cofounder and shareholder of medical technology companies Nocturne GmbH and Motognosis GmbH. He is named as inventor on several patent applications describing MS biomarkers, visual perceptive computing based motor function analysis, and retinal image analysis.PB reports no disclosures.MR The Medical University of Innsbruck and the University Hospital Innsbruck receive payments for antibody assays (AQP4 and other anti-neuronal and anti-glial antibodies) and for AQP4 antibody validation assays organized by Euroimmun (Luebeck, Germany).SJ was indirectly supported by grants from Dietmar Hopp Foundation, Merck Serono and German Ministry of Education and Research (to Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany; Prof. B. Wildemann).FP served on the scientific advisory boards of Novartis and MedImmune; received travel funding and\/or speaker honoraria from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis\/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an associate editor of <i>Neurology: Neuroimmunology & Neuroinflammation<\/i>; is an academic editor of <i>PLoS ONE<\/i>; consulted for Sanofi Genzyme, Biogen, MedImmune, Shire, and Alexion; received research support from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis\/Geynzme, Alexion, and Merck Serono; and received research support from the German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy-Jackson Charitable Foundation, and NMSS.JBS has received travel grants and speaking honoraria from Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi Genzyme, Teva Pharmaceuticals, Roche, and Novartis, none of them related to this project.JK received speaker fees, research support, travel support, and\/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_189140 \/ 1), University of Basel, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi, Teva.KR received research support from Novartis, Merck Serono, German Ministry of Education and Research, European Union (821283-2), Stiftung Charit\u00e9 (BIH Clinical Fellow Program) and Arthur Arnstein Foundation; received speaker honoraria and travel grants from Bayer, Biogen Idec, Merck Serono, sanofi-aventis\/Genzyme, Teva, Roche, Novartis, and Guthy Jackson Charitable Foundation.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"105"}}