{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:22:47Z","timestamp":1791238967095,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T00:00:00Z","timestamp":1456876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%\u201325% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients.<\/jats:p>","DOI":"10.3390\/ijms17030273","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T11:20:05Z","timestamp":1456917605000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["The Immunology of Neuromyelitis Optica\u2014Current Knowledge, Clinical Implications, Controversies and Future Perspectives"],"prefix":"10.3390","volume":"17","author":[{"given":"Michalina","family":"Jasiak-Zatonska","sequence":"first","affiliation":[{"name":"Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Kalinowska-Lyszczarz","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slawomir","family":"Michalak","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland"},{"name":"Neuroimmunological Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Kozubski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1212\/WNL.53.5.1107","article-title":"The clinical course of neuromyelitis optica (Devic\u2019s syndrome)","volume":"53","author":"Wingerchuk","year":"1999","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S1474-4422(07)70216-8","article-title":"The spectrum of neuromyelitis optica","volume":"6","author":"Wingerchuk","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1212\/01.wnl.0000216139.44259.74","article-title":"Revised diagnostic criteria for neuromyelitis optica","volume":"66","author":"Wingerchuk","year":"2006","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-10-8","article-title":"The history of neuromyelitis optica","volume":"10","author":"Jarius","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","article-title":"A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis","volume":"364","author":"Lennon","year":"2004","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1084\/jem.20050304","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume":"202","author":"Lennon","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1212\/01.CON.0000389937.69413.15","article-title":"Neuromyelitis spectrum disorders","volume":"16","author":"Wingerchuk","year":"2010","journal-title":"Contin. Lifelong Learn. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S1474-4422(12)70133-3","article-title":"Aquaporin 4 and neuromyelitis optica","volume":"11","author":"Papadopoulos","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1212\/WNL.0b013e3181ea9f15","article-title":"Familial neuromyelitis optica","volume":"75","author":"Matiello","year":"2010","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tzartos, J.S., Stergiou, C., Kilidireas, K., Zisimopoulou, P., Thomaidis, T., and Tzartos, S.J. (2013). Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074773"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Saadoun, S., Waters, P., Owens, G.P., Bennett, J.L., Vincent, A., and Papadopoulos, M.C. (2014). Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol. Commun., 2.","DOI":"10.1186\/2051-5960-2-35"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/brain\/awf151","article-title":"A role for humoral mechanisms in the pathogenesis of Devic\u2019s neuromyelitis optica","volume":"125","author":"Lucchinetti","year":"2002","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/ana.22686","article-title":"Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain","volume":"71","author":"Saadoun","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.brainresrev.2004.12.008","article-title":"Macrophages and neurodegeneration","volume":"48","author":"Hendriks","year":"2005","journal-title":"Brain Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/ana.21837","article-title":"Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo","volume":"66","author":"Bradl","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00281-009-0186-z","article-title":"Th17 cells in autoimmune demyelinating disease","volume":"32","author":"Segal","year":"2010","journal-title":"Semin. Immunopathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.jocn.2011.01.031","article-title":"Interleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse","volume":"18","author":"Wang","year":"2011","journal-title":"J. Clin. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jneuroim.2011.03.009","article-title":"Increased memory Th17 cells in patients with neuromyelitis optica and multiple sclerosis","volume":"234","author":"Li","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00401-012-0986-4","article-title":"Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss","volume":"123","author":"Ratelade","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1073\/pnas.1017385108","article-title":"Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica","volume":"108","author":"Chihara","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ana.21802","article-title":"Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica","volume":"66","author":"Bennett","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1152\/physrev.00011.2013","article-title":"Physiological roles of aquaporin-4 in brain","volume":"93","author":"Nagelhus","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7437","DOI":"10.1073\/pnas.0902725106","article-title":"Crystal structure of human aquaporin 4 at 1.8 \u00c5 and its mechanism of conductance","volume":"106","author":"Ho","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","first-page":"99","article-title":"Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: Current status of the assays","volume":"15","author":"Waters","year":"2008","journal-title":"Int. MS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/glia.20855","article-title":"Aquaporin-4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies","volume":"57","author":"Nicchia","year":"2009","journal-title":"Glia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16516","DOI":"10.1074\/jbc.M111.227298","article-title":"Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1\/M23 isoforms and orthogonal arrays","volume":"286","author":"Crane","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13829","DOI":"10.1074\/jbc.M112.344325","article-title":"Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays","volume":"287","author":"Phuan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/brain\/awm062","article-title":"Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: A study on antibody titre","volume":"130","author":"Takahashi","year":"2007","journal-title":"Brain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1093\/brain\/awn240","article-title":"Antibody to aquaporin-4 in the long-term course of neuromyelitis optica","volume":"131","author":"Jarius","year":"2008","journal-title":"Brain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.neuroscience.2009.08.032","article-title":"Neurological autoimmunity targeting aquaporin-4","volume":"168","author":"Hinson","year":"2010","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1084\/jem.20081241","article-title":"Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2","volume":"205","author":"Hinson","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.4049\/jimmunol.181.8.5730","article-title":"Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment","volume":"181","author":"Vincent","year":"2008","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1620\/tjem.215.55","article-title":"A prominent elevation of glial fibrillary acidic protein in the cerebrospinal fluid during relapse in neuromyelitis optica","volume":"215","author":"Takano","year":"2008","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/jnnp.2008.150698","article-title":"Marked increase in cerebrospinal fluid glial fibrillar acidic protein in neuromyelitis optica: An astrocytic damage marker","volume":"80","author":"Misu","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/brain\/awp309","article-title":"Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice","volume":"133","author":"Saadoun","year":"2010","journal-title":"Brain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jneuroim.2014.07.001","article-title":"Complement activation in patients with neuromyelitis optica","volume":"274","author":"Nytrova","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jneuroim.2010.11.010","article-title":"Enhanced complement consumption in neuromyelitis optica and Behcet\u2019s disease patients","volume":"233","author":"Pehlivan","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jneuroim.2012.09.002","article-title":"Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica","volume":"254","author":"Kuroda","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbrc.2009.06.085","article-title":"Neuromyelitis optica: Passive transfer to rats by human immunoglobulin","volume":"386","author":"Kinoshita","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jarius, S., Ruprecht, K., Wildemann, B., Kuempfel, T., Ringelstein, M., Geis, C., Kleiter, I., Kleinschnitz, C., Berthele, A., and Brettschneider, J. (2012). Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J. Neuroinflammation, 9.","DOI":"10.1186\/1742-2094-9-14"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jarius, S., Franciotta, D., Paul, F., Ruprecht, K., Bergamaschi, R., Rommer, P.S., Reuss, R., Probst, C., Kristoferitsch, W., and Wandinger, K.P. (2010). Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: Frequency, origin, and diagnostic relevance. J. Neuroinflamm., 7.","DOI":"10.1186\/1742-2094-7-52"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jns.2010.10.013","article-title":"A serological analysis of viral and bacterial infections associated with neuromyelitis optica","volume":"300","author":"Koga","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_44","first-page":"111","article-title":"Interrelationships of the pia mater and the perivascular (Virchow\u2013Robin) spaces in the human cerebrum","volume":"170","author":"Zhang","year":"1990","journal-title":"J. Anat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1006\/exnr.1993.1059","article-title":"Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system","volume":"120","author":"Broadwell","year":"1993","journal-title":"Exp. Neurol."},{"key":"ref_46","first-page":"895","article-title":"Lack of blood\u2013brain barrier properties in microvessels of the prelaminar optic nerve head","volume":"42","author":"Schlingemann","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ana.22421","article-title":"The blood\u2013spinal cord barrier: Morphology and clinical implications","volume":"70","author":"Bartanusz","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1093\/brain\/awm047","article-title":"Loss of aquaporin 4 in lesions of neuromyelitis optica: Distinction from multiple sclerosis","volume":"130","author":"Misu","year":"2007","journal-title":"Brain"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1001\/archneur.65.7.913","article-title":"Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis","volume":"65","author":"Waters","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Paul, F., Jarius, S., Aktas, O., Bluthner, M., Bauer, O., Appelhans, H., Franciotta, D., Bergamaschi, R., Littleton, E., and Palace, J. (2007). Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040133"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jneuroim.2008.03.009","article-title":"Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay","volume":"196","author":"Hayakawa","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1212\/WNL.0b013e318248dec1","article-title":"Serologic diagnosis of NMO A multicenter comparison of aquaporin-4-IgG assays","volume":"78","author":"Waters","year":"2012","journal-title":"Neurology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.neuroscience.2004.06.076","article-title":"Freeze-fracture and immunogold analysis of aquaporin-4 (AQP4) square arrays, with models of AQP4 lattice assembly","volume":"129","author":"Rash","year":"2004","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1001\/archneurol.2009.188","article-title":"Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells","volume":"66","author":"Hinson","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jns.2009.02.371","article-title":"Multimodality-evoked potential study of anti-aquaporin-4 antibody-positive and-negative multiple sclerosis patients","volume":"281","author":"Watanabe","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/ana.20770","article-title":"Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis","volume":"59","author":"Weinshenker","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.1212\/NXI.0000000000000134","article-title":"Update on biomarkers in neuromyelitis optica","volume":"2","author":"Melamed","year":"2015","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jneuroim.2014.06.003","article-title":"Development of a cell-based assay for the detection of anti-aquaporin 1 antibodies in neuromyelitis optica spectrum disorders","volume":"273","author":"Long","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000364904","article-title":"Aquaporin-1 Antibody in Neuromyelitis Optica Patients","volume":"72","author":"Tzartos","year":"2014","journal-title":"Eur. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Mader, S., Gredler, V., Schanda, K., Rostasy, K., Dujmovic, I., Pfaller, K., Lutterotti, A., Jarius, S., Di Pauli, F., and Kuenz, B. (2011). Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J. Neuroinflamm., 8.","DOI":"10.1186\/1742-2094-8-184"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1212\/WNL.0000000000000101","article-title":"Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders","volume":"82","author":"Sato","year":"2014","journal-title":"Neurology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.1212\/NXI.0000000000000040","article-title":"Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis","volume":"1","author":"Ramanathan","year":"2014","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/1352458511431077","article-title":"The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease","volume":"18","author":"Wingerchuk","year":"2012","journal-title":"Mult. Scler. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1177\/1352458510379247","article-title":"Cytokine and chemokine profiles in neuromyelitis optica: Significance of interleukin-6","volume":"16","author":"Uzawa","year":"2010","journal-title":"Mult. Scler. Houndmills Basingstoke Engl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1007\/s00415-009-5274-4","article-title":"Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis","volume":"256","author":"Uzawa","year":"2009","journal-title":"J. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.cca.2013.03.020","article-title":"Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks","volume":"421","author":"Uzawa","year":"2013","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1159\/000339302","article-title":"Notable increased cerebrospinal fluid levels of soluble interleukin-6 receptors in neuromyelitis optica","volume":"19","author":"Wang","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1136\/jnnp.2011.241760","article-title":"CSF interleukin-6 level predicts recovery from neuromyelitis optica relapse","volume":"83","author":"Uzawa","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jneuroim.2011.04.009","article-title":"Increased serum matrix metalloproteinase-9 in neuromyelitis optica: Implication of disruption of blood-brain barrier","volume":"236","author":"Hosokawa","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1136\/jnnp-2011-300434","article-title":"Sera from neuromyelitis optica patients disrupt the blood-brain barrier","volume":"83","author":"Shimizu","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1001\/archneurol.2011.148","article-title":"Markedly elevated soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 levels, and blood-brain barrier breakdown in neuromyelitis optica","volume":"68","author":"Uzawa","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/mus.21197","article-title":"Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica","volume":"39","author":"McKeon","year":"2009","journal-title":"Muscle Nerve"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1001\/archneur.65.5.629","article-title":"Aquaporin-4 autoantibodies in a paraneoplastic context","volume":"65","author":"Pittock","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/1756285611398939","article-title":"Current and future treatment approaches for neuromyelitis optica","volume":"4","author":"Collongues","year":"2011","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1001\/archneurol.2009.175","article-title":"Treatment of neuromyelitis optica with mycophenolate mofetil: Retrospective analysis of 24 patients","volume":"66","author":"Jacob","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1001\/archneur.63.7.957","article-title":"Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease)","volume":"63","author":"Ramanathan","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1017\/S0317167100053932","article-title":"Devic\u2019s neuromyelitis optica treated with intravenous gamma globulin (IVIG)","volume":"31","author":"Bakker","year":"2004","journal-title":"Can. J. Neurol. Sci. J. Can. Sci. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/archneur.65.11.noc80069","article-title":"Treatment of neuromyelitis optica with rituximab: Retrospective analysis of 25 patients","volume":"65","author":"Jacob","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/ana.22657","article-title":"Anti-Aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica","volume":"71","author":"Tradtrantip","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S1474-4422(13)70076-0","article-title":"Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: An open-label pilot study","volume":"12","author":"Pittock","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1212\/WNL.0000000000000317","article-title":"Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica A pilot study","volume":"82","author":"Araki","year":"2014","journal-title":"Neurology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/3\/273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:20:00Z","timestamp":1760210400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/3\/273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,2]]},"references-count":81,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3]]}},"alternative-id":["ijms17030273"],"URL":"https:\/\/doi.org\/10.3390\/ijms17030273","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,2]]}}}