{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:59:49Z","timestamp":1792724389384,"version":"4.5.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008087","name":"Guthy-Jackson Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008087","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutscher Akademischer Austauschdienst"},{"DOI":"10.13039\/100016888","name":"Bayer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016888","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017270","name":"NeuroCure Cluster of Excellence","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100017270","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002839","name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002839","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), neutrophils are found in CNS lesions. We previously demonstrated that NMOSD neutrophils show functional deficiencies. Thus, we hypothesized that neutrophil accumulation in the CNS may be facilitated by impairments affecting mechanisms of neutrophil death.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To evaluate cell death in blood neutrophils from aquaporin-4 (AQP4)-IgG-seropositive NMOSD and MOGAD patients as well as matched healthy controls (HC) using in vitro assays.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Twenty-eight AQP4\u2009+\u2009NMOSD and 19 MOGAD patients in stable disease phase as well as 45 age- and sex-matched HC were prospectively recruited. To induce cell death, isolated neutrophils were cultured with\/without phorbol 12-myristate 13-acetate (PMA). Spontaneous and PMA-induced NETosis and apoptosis were analyzed using 7-AAD and annexin-V by flow cytometry. Caspase-3 was assessed by western blot. Myeloperoxidase-DNA complexes (MPO-DNA), MPO and elastase were evaluated by ELISA, and cell-free DNA (cfDNA) by a fluorescence-based assay. Reactive oxygen species (ROS) were evaluated by a dihydrorhodamine 123-based cytometric assay. Serum GM-CSF, IL-6, IL-8, IL-15, TNF-\u0251 and IL-10 were evaluated by multiplex assays, and neurofilament light chain (NfL) by single-molecule array assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In response to PMA, neutrophils from AQP4\u2009+\u2009NMOSD but not from MOGAD patients showed an increased survival, and subsequent reduced cell death (29.6% annexin V<jats:sup>+<\/jats:sup> 7-AAD<jats:sup>+<\/jats:sup>) when compared to HC (44.7%, <jats:italic>p<\/jats:italic>\u2009=\u20090.0006). However, AQP4\u2009+\u2009NMOSD also showed a mild increase in annexin V<jats:sup>+<\/jats:sup> 7-AAD<jats:sup>\u2212<\/jats:sup> early apoptotic neutrophils (24.5%) compared to HC (20.8%, <jats:italic>p<\/jats:italic>\u2009=\u20090.048). PMA-induced reduction of caspase-3 activation was more pronounced in HC (<jats:italic>p<\/jats:italic>\u2009=\u20090.020) than in AQP4\u2009+\u2009NMOSD neutrophils (<jats:italic>p<\/jats:italic>\u2009=\u20090.052). No differences were observed in neutrophil-derived MPO-DNA or serum levels of MPO, elastase, IL-6, IL-8 and TNF-\u0251. IL-15 levels were increased in both groups of patients. In AQP4\u2009+\u2009NMOSD, an increase in cfDNA, GM-CSF and IL-10 was found in serum. A positive correlation among cfDNA and NfL was found in AQP4\u2009+\u2009NMOSD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>AQP4\u2009+\u2009NMOSD neutrophils showed an increased survival capacity in response to PMA when compared to matched HC neutrophils. Although the data indicate that the apoptotic but not the NETotic response is altered in these neutrophils, additional evaluations\u00a0are required to validate\u00a0this observation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-022-02600-0","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T07:11:37Z","timestamp":1664608297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Impaired response of blood neutrophils to cell-death stimulus differentiates AQP4-IgG-seropositive NMOSD from MOGAD"],"prefix":"10.1186","volume":"19","author":[{"given":"Maria","family":"Schroeder-Castagno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Del Rio-Serrato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvina","family":"Romero-Su\u00e1rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Alvarez-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankelien-Solveig","family":"Duchow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Bellmann-Strobl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Ruprecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hastermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Gr\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Wildemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Jarius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Schmitz-H\u00fcbsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedemann","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Infante-Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"2600_CR1","doi-asserted-by":"publisher","first-page":"888","DOI":"10.3389\/fneur.2018.00888","volume":"9","author":"N Borisow","year":"2018","unstructured":"Borisow N, Mori M, Kuwabara S, Scheel M, Paul F. Diagnosis and treatment of NMO spectrum disorder and MOG-encephalomyelitis. Front Neurol. 2018;9:888. https:\/\/doi.org\/10.3389\/fneur.2018.00888.","journal-title":"Front Neurol"},{"issue":"1","key":"2600_CR2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41572-020-0214-9","volume":"6","author":"S Jarius","year":"2020","unstructured":"Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers. 2020;6(1):85. https:\/\/doi.org\/10.1038\/s41572-020-0214-9.","journal-title":"Nat Rev Dis Primers"},{"issue":"6","key":"2600_CR3","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1111\/bpa.12084","volume":"23","author":"S Jarius","year":"2013","unstructured":"Jarius S, Wildemann B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol. 2013;23(6):661\u201383. https:\/\/doi.org\/10.1111\/bpa.12084.","journal-title":"Brain Pathol"},{"issue":"2","key":"2600_CR4","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","volume":"85","author":"DM Wingerchuk","year":"2015","unstructured":"Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177\u201389. https:\/\/doi.org\/10.1212\/WNL.0000000000001729.","journal-title":"Neurology"},{"issue":"1","key":"2600_CR5","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s12974-018-1144-2","volume":"15","author":"S Jarius","year":"2018","unstructured":"Jarius S, Paul F, Aktas O, et al. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation. 2018;15(1):134. https:\/\/doi.org\/10.1186\/s12974-018-1144-2.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"2600_CR6","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12974-016-0717-1","volume":"13","author":"S Jarius","year":"2016","unstructured":"Jarius S, Ruprecht K, Kleiter I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflam. 2016;13(1):279. https:\/\/doi.org\/10.1186\/s12974-016-0717-1.","journal-title":"J Neuroinflam"},{"issue":"1","key":"2600_CR7","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1186\/s12974-016-0718-0","volume":"13","author":"S Jarius","year":"2016","unstructured":"Jarius S, Ruprecht K, Kleiter I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflam. 2016;13(1):280. https:\/\/doi.org\/10.1186\/s12974-016-0718-0.","journal-title":"J Neuroinflam"},{"issue":"1","key":"2600_CR8","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1186\/s12974-016-0719-z","volume":"13","author":"S Jarius","year":"2016","unstructured":"Jarius S, Kleiter I, Ruprecht K, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: Brainstem involvement - frequency, presentation and outcome. J Neuroinflam. 2016;13(1):281. https:\/\/doi.org\/10.1186\/s12974-016-0719-z.","journal-title":"J Neuroinflam"},{"issue":"1","key":"2600_CR9","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1186\/s12974-016-0720-6","volume":"13","author":"F Pache","year":"2016","unstructured":"Pache F, Zimmermann H, Mikolajczak J, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflam. 2016;13(1):282. https:\/\/doi.org\/10.1186\/s12974-016-0720-6.","journal-title":"J Neuroinflam"},{"issue":"9","key":"2600_CR10","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/S1474-4422(21)00218-0","volume":"20","author":"R Marignier","year":"2021","unstructured":"Marignier R, Hacohen Y, Cobo-Calvo A, et al. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021;20(9):762\u201372. https:\/\/doi.org\/10.1016\/S1474-4422(21)00218-0.","journal-title":"Lancet Neurol"},{"issue":"Pt 7","key":"2600_CR11","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1093\/brain\/awf151","volume":"125","author":"CF Lucchinetti","year":"2002","unstructured":"Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic\u2019s neuromyelitis optica. Brain. 2002;125(Pt 7):1450\u201361. https:\/\/doi.org\/10.1093\/brain\/awf151.","journal-title":"Brain"},{"issue":"5","key":"2600_CR12","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1093\/brain\/awl371","volume":"130","author":"SF Roemer","year":"2007","unstructured":"Roemer SF, Parisi JE, Lennon VA, et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain. 2007;130(5):1194\u2013205. https:\/\/doi.org\/10.1093\/brain\/awl371.","journal-title":"Brain"},{"issue":"6","key":"2600_CR13","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00401-013-1116-7","volume":"125","author":"T Misu","year":"2013","unstructured":"Misu T, H\u00f6ftberger R, Fujihara K, et al. Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica. Acta Neuropathol. 2013;125(6):815\u201327. https:\/\/doi.org\/10.1007\/s00401-013-1116-7.","journal-title":"Acta Neuropathol"},{"issue":"1\u20132","key":"2600_CR14","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jns.2011.03.038","volume":"306","author":"S Jarius","year":"2011","unstructured":"Jarius S, Paul F, Franciotta D, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci. 2011;306(1\u20132):82\u201390. https:\/\/doi.org\/10.1016\/j.jns.2011.03.038.","journal-title":"J Neurol Sci"},{"key":"2600_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.628024","volume":"12","author":"E Carnero Contentti","year":"2021","unstructured":"Carnero Contentti E, Delgado-Garc\u00eda G, Criniti J, et al. An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD. Front Immunol. 2021;12: 628024. https:\/\/doi.org\/10.3389\/fimmu.2021.628024.","journal-title":"Front Immunol"},{"key":"2600_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102345","volume":"45","author":"C Benetou","year":"2020","unstructured":"Benetou C, Berti F, Hemingway C, Hacohen Y, Lim M. Neutrophil-to-lymphocyte ratio correlates with disease activity in myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) in children. Mult Scler Relat Disord. 2020;45: 102345. https:\/\/doi.org\/10.1016\/j.msard.2020.102345.","journal-title":"Mult Scler Relat Disord"},{"issue":"Pt 2","key":"2600_CR17","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1093\/brain\/awp309","volume":"133","author":"S Saadoun","year":"2010","unstructured":"Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133(Pt 2):349\u201361. https:\/\/doi.org\/10.1093\/brain\/awp309.","journal-title":"Brain"},{"issue":"3","key":"2600_CR18","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/ana.22686","volume":"71","author":"S Saadoun","year":"2012","unstructured":"Saadoun S, Waters P, MacDonald C, et al. Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain. Ann Neurol. 2012;71(3):323\u201333. https:\/\/doi.org\/10.1002\/ana.22686.","journal-title":"Ann Neurol"},{"key":"2600_CR19","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/2051-5960-1-5","volume":"1","author":"M Kitic","year":"2013","unstructured":"Kitic M, Hochmeister S, Wimmer I, et al. Intrastriatal injection of interleukin-1 beta triggers the formation of neuromyelitis optica-like lesions in NMO-IgG seropositive rats. Acta Neuropathol Commun. 2013;1:5. https:\/\/doi.org\/10.1186\/2051-5960-1-5.","journal-title":"Acta Neuropathol Commun"},{"key":"2600_CR20","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1172\/JCI141694","volume":"131","author":"A Winkler","year":"2021","unstructured":"Winkler A, Wrzos C, Haberl M, et al. Blood-brain barrier resealing in neuromyelitis optica occurs independently of astrocyte regeneration. J Clin Invest. 2021;131:5. https:\/\/doi.org\/10.1172\/JCI141694.","journal-title":"J Clin Invest"},{"issue":"4","key":"2600_CR21","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/ana.26327","volume":"91","author":"S Iwamoto","year":"2022","unstructured":"Iwamoto S, Itokazu T, Sasaki A, et al. RGMa Signal in Macrophages Induces Neutrophil-Related Astrocytopathy in NMO. Ann Neurol. 2022;91(4):532\u201347. https:\/\/doi.org\/10.1002\/ana.26327.","journal-title":"Ann Neurol"},{"issue":"12","key":"2600_CR22","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1177\/1352458512443994","volume":"18","author":"A Jacob","year":"2012","unstructured":"Jacob A, Saadoun S, Kitley J, et al. Detrimental role of granulocyte-colony stimulating factor in neuromyelitis optica: clinical case and histological evidence. Mult Scler. 2012;18(12):1801\u20133. https:\/\/doi.org\/10.1177\/1352458512443994.","journal-title":"Mult Scler"},{"issue":"6","key":"2600_CR23","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1002\/ana.22551","volume":"70","author":"H Zhang","year":"2011","unstructured":"Zhang H, Bennett JL, Verkman AS. Ex vivo spinal cord slice model of neuromyelitis optica reveals novel immunopathogenic mechanisms. Ann Neurol. 2011;70(6):943\u201354. https:\/\/doi.org\/10.1002\/ana.22551.","journal-title":"Ann Neurol"},{"issue":"4","key":"2600_CR24","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1177\/1352458512440060","volume":"18","author":"K Herges","year":"2012","unstructured":"Herges K, de Jong BA, Kolkowitz I, et al. Protective effect of an elastase inhibitor in a neuromyelitis optica-like disease driven by a peptide of myelin oligodendroglial glycoprotein. Mult Scler. 2012;18(4):398\u2013408. https:\/\/doi.org\/10.1177\/1352458512440060.","journal-title":"Mult Scler"},{"issue":"2","key":"2600_CR25","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1177\/1352458515586084","volume":"22","author":"L Hertwig","year":"2016","unstructured":"Hertwig L, Pache F, Romero-Suarez S, et al. Distinct functionality of neutrophils in multiple sclerosis and neuromyelitis optica. Mult Scler. 2016;22(2):160\u201373. https:\/\/doi.org\/10.1177\/1352458515586084.","journal-title":"Mult Scler"},{"key":"2600_CR26","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.3389\/fimmu.2018.01694","volume":"9","author":"P Piatek","year":"2018","unstructured":"Piatek P, Domowicz M, Lewkowicz N, et al. C5a-preactivated neutrophils are critical for autoimmune-induced astrocyte dysregulation in neuromyelitis optica spectrum disorder. Front Immunol. 2018;9:1694. https:\/\/doi.org\/10.3389\/fimmu.2018.01694.","journal-title":"Front Immunol"},{"key":"2600_CR27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1212\/NXI.0000000000001149","volume":"9","author":"H Murata","year":"2022","unstructured":"Murata H, Kinoshita M, Yasumizu Y, et al. Cell-Free DNA derived from neutrophils triggers type 1 interferon signature in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflam. 2022;9:3. https:\/\/doi.org\/10.1212\/NXI.0000000000001149.","journal-title":"Neurol Neuroimmunol Neuroinflam"},{"issue":"2","key":"2600_CR28","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1083\/jcb.200606027","volume":"176","author":"TA Fuchs","year":"2007","unstructured":"Fuchs TA, Abed U, Goosmann C, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176(2):231\u201341. https:\/\/doi.org\/10.1083\/jcb.200606027.","journal-title":"J Cell Biol"},{"key":"2600_CR29","doi-asserted-by":"publisher","first-page":"649693","DOI":"10.3389\/fimmu.2021.649693","volume":"12","author":"M Fresneda Alarcon","year":"2021","unstructured":"Fresneda Alarcon M, McLaren Z, Wright HL. Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O. Front Immunol. 2021;12:649693. https:\/\/doi.org\/10.3389\/fimmu.2021.649693.","journal-title":"Front Immunol"},{"key":"2600_CR30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1742-2094-9-14","volume":"9","author":"S Jarius","year":"2012","unstructured":"Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflam. 2012;9:14. https:\/\/doi.org\/10.1186\/1742-2094-9-14.","journal-title":"J Neuroinflam"},{"issue":"11","key":"2600_CR31","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1212\/wnl.33.11.1444","volume":"33","author":"JF Kurtzke","year":"1983","unstructured":"Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444\u201352. https:\/\/doi.org\/10.1212\/wnl.33.11.1444.","journal-title":"Neurology"},{"key":"2600_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.875456","author":"T Akaishi","year":"2022","unstructured":"Akaishi T, Ishii T, Aoki M, Nakashima I. Calculating and comparing the annualized relapse rate and estimating the confidence interval in relapsing neurological diseases. Front Neurol. 2022. https:\/\/doi.org\/10.3389\/fneur.2022.875456.","journal-title":"Front Neurol"},{"issue":"1\u20132","key":"2600_CR33","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jns.2010.01.002","volume":"291","author":"S Jarius","year":"2010","unstructured":"Jarius S, Probst C, Borowski K, et al. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci. 2010;291(1\u20132):52\u20136. https:\/\/doi.org\/10.1016\/j.jns.2010.01.002.","journal-title":"J Neurol Sci"},{"issue":"1","key":"2600_CR34","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s12974-020-01824-2","volume":"17","author":"S Jarius","year":"2020","unstructured":"Jarius S, Pellkofer H, Siebert N, et al. Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients. J Neuroinflam. 2020;17(1):261. https:\/\/doi.org\/10.1186\/s12974-020-01824-2.","journal-title":"J Neuroinflam"},{"key":"2600_CR35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/0471142735.im0723s19","volume":"7","author":"RA Clark","year":"2001","unstructured":"Clark RA, Nauseef WM. Isolation and functional analysis of neutrophils. Curr Protoc Immunol. 2001;7:23. https:\/\/doi.org\/10.1002\/0471142735.im0723s19.","journal-title":"Curr Protoc Immunol"},{"issue":"6","key":"2600_CR36","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nm.1959","volume":"15","author":"K Kessenbrock","year":"2009","unstructured":"Kessenbrock K, Krumbholz M, Sch\u00f6nermarck U, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;15(6):623\u20135. https:\/\/doi.org\/10.1038\/nm.1959.","journal-title":"Nat Med"},{"issue":"13","key":"2600_CR37","doi-asserted-by":"publisher","first-page":"e1299","DOI":"10.1212\/WNL.0000000000008160","volume":"93","author":"M Watanabe","year":"2019","unstructured":"Watanabe M, Nakamura Y, Michalak Z, et al. Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD. Neurology. 2019;93(13):e1299\u2013311. https:\/\/doi.org\/10.1212\/WNL.0000000000008160.","journal-title":"Neurology"},{"issue":"1","key":"2600_CR38","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12974-021-02138-7","volume":"18","author":"P Schindler","year":"2021","unstructured":"Schindler P, Grittner U, Oechtering J, et al. Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. J Neuroinflammation. 2021;18(1):105. https:\/\/doi.org\/10.1186\/s12974-021-02138-7.","journal-title":"J Neuroinflammation"},{"issue":"Pt 7","key":"2600_CR39","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1093\/brain\/awf151","volume":"125","author":"CF Lucchinetti","year":"2002","unstructured":"Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic\u2019s neuromyelitis optica. Brain. 2002;125(Pt 7):1450\u201361. https:\/\/doi.org\/10.1093\/brain\/awf151.","journal-title":"Brain"},{"issue":"2","key":"2600_CR40","doi-asserted-by":"publisher","first-page":"869","DOI":"10.4049\/jimmunol.1700905","volume":"200","author":"S Gupta","year":"2018","unstructured":"Gupta S, Chan DW, Zaal KJ, Kaplan MJ. A high-throughput real-time imaging technique to quantify NETosis and distinguish mechanisms of cell death in human neutrophils. J Immunol. 2018;200(2):869\u201379. https:\/\/doi.org\/10.4049\/jimmunol.1700905.","journal-title":"J Immunol"},{"key":"2600_CR41","doi-asserted-by":"publisher","first-page":"e24437","DOI":"10.7554\/eLife.24437","volume":"6","author":"EF Kenny","year":"2017","unstructured":"Kenny EF, Herzig A, Kr\u00fcger R, et al. Diverse stimuli engage different neutrophil extracellular trap pathways. Elife. 2017;6:e24437. https:\/\/doi.org\/10.7554\/eLife.24437.","journal-title":"Elife"},{"issue":"2","key":"2600_CR42","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/cr.2010.150","volume":"21","author":"Q Remijsen","year":"2011","unstructured":"Remijsen Q, Berghe TV, Wirawan E, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res. 2011;21(2):290\u2013304. https:\/\/doi.org\/10.1038\/cr.2010.150.","journal-title":"Cell Res"},{"issue":"5","key":"2600_CR43","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1083\/jcb.201203170","volume":"198","author":"V Brinkmann","year":"2012","unstructured":"Brinkmann V, Zychlinsky A. Neutrophil extracellular traps: Is immunity the second function of chromatin? J Cell Biol. 2012;198(5):773\u201383. https:\/\/doi.org\/10.1083\/jcb.201203170.","journal-title":"J Cell Biol"},{"issue":"4","key":"2600_CR44","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1182\/blood-2013-09-526707","volume":"123","author":"DN Douda","year":"2014","unstructured":"Douda DN, Yip L, Khan MA, Grasemann H, Palaniyar N. Akt is essential to induce NADPH-dependent NETosis and to switch the neutrophil death to apoptosis. Blood. 2014;123(4):597\u2013600. https:\/\/doi.org\/10.1182\/blood-2013-09-526707.","journal-title":"Blood"},{"issue":"1","key":"2600_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41420-018-0048-3","volume":"4","author":"D Azzouz","year":"2018","unstructured":"Azzouz D, Khan MA, Sweezey N, Palaniyar N. Two-in-one: UV radiation simultaneously induces apoptosis and NETosis. Cell Death Discovery. 2018;4(1):1\u201313. https:\/\/doi.org\/10.1038\/s41420-018-0048-3.","journal-title":"Cell Death Discovery"},{"issue":"5","key":"2600_CR46","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.4049\/jimmunol.1300436","volume":"191","author":"C Farrera","year":"2013","unstructured":"Farrera C, Fadeel B. Macrophage clearance of neutrophil extracellular traps is a silent process. J Immunol. 2013;191(5):2647\u201356. https:\/\/doi.org\/10.4049\/jimmunol.1300436.","journal-title":"J Immunol"},{"issue":"2","key":"2600_CR47","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nchembio.496","volume":"7","author":"A Hakkim","year":"2011","unstructured":"Hakkim A, Fuchs TA, Martinez NE, et al. Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation. Nat Chem Biol. 2011;7(2):75\u20137. https:\/\/doi.org\/10.1038\/nchembio.496.","journal-title":"Nat Chem Biol"},{"issue":"2","key":"2600_CR48","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1136\/thoraxjnl-2017-210134","volume":"73","author":"RD Gray","year":"2018","unstructured":"Gray RD, Hardisty G, Regan KH, et al. Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis. Thorax. 2018;73(2):134\u201344. https:\/\/doi.org\/10.1136\/thoraxjnl-2017-210134.","journal-title":"Thorax"},{"issue":"3","key":"2600_CR49","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1134\/S0022093021030017","volume":"57","author":"EM Noseykina","year":"2021","unstructured":"Noseykina EM, Schepetkin IA, Atochin DN. Molecular mechanisms for regulation of neutrophil apoptosis under normal and pathological conditions. J Evol Biochem Physiol. 2021;57(3):429\u201350. https:\/\/doi.org\/10.1134\/S0022093021030017.","journal-title":"J Evol Biochem Physiol"},{"issue":"3","key":"2600_CR50","doi-asserted-by":"publisher","first-page":"e32439","DOI":"10.1371\/journal.pone.0032439","volume":"7","author":"M Abdgawad","year":"2012","unstructured":"Abdgawad M, Pettersson \u00c5, Gunnarsson L, et al. Decreased neutrophil apoptosis in quiescent ANCA-associated systemic vasculitis. PLoS ONE. 2012;7(3):e32439. https:\/\/doi.org\/10.1371\/journal.pone.0032439.","journal-title":"PLoS ONE"},{"issue":"5","key":"2600_CR51","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1097\/00024382-200005000-00003","volume":"13","author":"AE Brannigan","year":"2000","unstructured":"Brannigan AE, O\u2019Connell PR, Hurley H, et al. Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock. 2000;13(5):361\u20136. https:\/\/doi.org\/10.1097\/00024382-200005000-00003.","journal-title":"Shock"},{"issue":"3","key":"2600_CR52","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/bjc.2017.173","volume":"117","author":"L Barrera","year":"2017","unstructured":"Barrera L, Montes-Serv\u00edn E, Hernandez-Martinez JM, et al. CD47 overexpression is associated with decreased neutrophil apoptosis\/phagocytosis and poor prognosis in non-small-cell lung cancer patients. Br J Cancer. 2017;117(3):385\u201397. https:\/\/doi.org\/10.1038\/bjc.2017.173.","journal-title":"Br J Cancer"},{"issue":"10","key":"2600_CR53","doi-asserted-by":"publisher","first-page":"6198","DOI":"10.4049\/jimmunol.0901264","volume":"183","author":"A Paunel-G\u00f6rg\u00fcl\u00fc","year":"2009","unstructured":"Paunel-G\u00f6rg\u00fcl\u00fc A, Z\u00f6rnig M, L\u00f6gters T, et al. Mcl-1-mediated impairment of the intrinsic apoptosis pathway in circulating neutrophils from critically ill patients can be overcome by Fas stimulation. J Immunol. 2009;183(10):6198\u2013206. https:\/\/doi.org\/10.4049\/jimmunol.0901264.","journal-title":"J Immunol"},{"issue":"1","key":"2600_CR54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1189\/jlb.68.1.15","volume":"68","author":"S O\u2019Neill","year":"2000","unstructured":"O\u2019Neill S, O\u2019Neill AJ, Conroy E, Brady HR, Fitzpatrick JM, Watson RW. Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis. J Leukoc Biol. 2000;68(1):15\u201320.","journal-title":"J Leukoc Biol"},{"key":"2600_CR55","doi-asserted-by":"publisher","first-page":"502","DOI":"10.3389\/fimmu.2019.00502","volume":"10","author":"B Duvvuri","year":"2019","unstructured":"Duvvuri B, Lood C. Cell-Free DNA as a biomarker in autoimmune rheumatic diseases. Front Immunol. 2019;10:502. https:\/\/doi.org\/10.3389\/fimmu.2019.00502.","journal-title":"Front Immunol"},{"key":"2600_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.584116","author":"HL Wright","year":"2021","unstructured":"Wright HL, Lyon M, Chapman EA, Moots RJ, Edwards SW. Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species, and neutrophil extracellular traps. Front Immunol. 2021. https:\/\/doi.org\/10.3389\/fimmu.2020.584116.","journal-title":"Front Immunol"},{"issue":"9","key":"2600_CR57","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1096\/fj.05-5395fje","volume":"20","author":"PMC Dang","year":"2006","unstructured":"Dang PMC, Elbim C, Marie JC, Chiandotto M, Gougerot-Pocidalo MA, El-Benna J. Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1\/2 activity. FASEB J. 2006;20(9):1504\u20136. https:\/\/doi.org\/10.1096\/fj.05-5395fje.","journal-title":"FASEB J"},{"issue":"9","key":"2600_CR58","doi-asserted-by":"publisher","first-page":"3356","DOI":"10.1182\/blood.V90.9.3356","volume":"90","author":"M Keel","year":"1997","unstructured":"Keel M, Ungeth\u00fcm U, Steckholzer U, et al. Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood. 1997;90(9):3356\u201363.","journal-title":"Blood"},{"issue":"9","key":"2600_CR59","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1136\/jnnp-2018-317969","volume":"89","author":"K Kaneko","year":"2018","unstructured":"Kaneko K, Sato DK, Nakashima I, et al. CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications. J Neurol Neurosurg Psychiatry. 2018;89(9):927\u201336. https:\/\/doi.org\/10.1136\/jnnp-2018-317969.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"2600_CR60","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/sj.leu.2400607","volume":"11","author":"K Spiekermann","year":"1997","unstructured":"Spiekermann K, Roesler J, Emmendoerffer A, Elsner J, Welte K. Functional features of neutrophils induced by G-CSF and GM-CSF treatment: differential effects and clinical implications. Leukemia. 1997;11(4):466\u201378. https:\/\/doi.org\/10.1038\/sj.leu.2400607.","journal-title":"Leukemia"},{"issue":"4","key":"2600_CR61","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1159\/000494976","volume":"25","author":"Y Wei","year":"2018","unstructured":"Wei Y, Chang H, Li X, et al. Cytokines and tissue damage biomarkers in first-onset neuromyelitis optica spectrum disorders: significance of interleukin-6. NeuroImmunoModulation. 2018;25(4):215\u201324. https:\/\/doi.org\/10.1159\/000494976.","journal-title":"NeuroImmunoModulation"},{"key":"2600_CR62","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1212\/NXI.0000000000000852","volume":"7","author":"SS Yandamuri","year":"2020","unstructured":"Yandamuri SS, Jiang R, Sharma A, et al. High-throughput investigation of molecular and cellular biomarkers in NMOSD. Neurol Neuroimmunol Neuroinflam. 2020;7:5. https:\/\/doi.org\/10.1212\/NXI.0000000000000852.","journal-title":"Neurol Neuroimmunol Neuroinflam."},{"issue":"1","key":"2600_CR63","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1042\/bj3250147","volume":"325","author":"D Girard","year":"1997","unstructured":"Girard D, Paquin R, Beaulieu AD. Responsiveness of human neutrophils to interleukin-4: induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis. Biochem J. 1997;325(1):147\u201353.","journal-title":"Biochem J"},{"issue":"10","key":"2600_CR64","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1093\/intimm\/dxq434","volume":"22","author":"C Costantini","year":"2010","unstructured":"Costantini C, Micheletti A, Calzetti F, Perbellini O, Pizzolo G, Cassatella MA. Neutrophil activation and survival are modulated by interaction with NK cells. Int Immunol. 2010;22(10):827\u201338. https:\/\/doi.org\/10.1093\/intimm\/dxq434.","journal-title":"Int Immunol"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02600-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-022-02600-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02600-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T07:13:28Z","timestamp":1664608408000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-022-02600-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2600"],"URL":"https:\/\/doi.org\/10.1186\/s12974-022-02600-0","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]},"assertion":[{"value":"8 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was evaluated and approved by the Ethics Committee of the Charit\u00e9-Universit\u00e4tsmedizin Berlin (EA1\/041\/14, EA1\/163\/12). The participants provided their written informed consent to participate in this study.","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":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"239"}}