{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:03:25Z","timestamp":1784127805657,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271375"],"award-info":[{"award-number":["82271375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Objective<\/jats:title>\n \n Despite achieving complete peripheral B cell deletion after over 6\u2009months of rituximab therapy, a clinically significant minority of neuromyelitis optica spectrum disorder (NMOSD) patients experience breakthrough relapses, yet the underlying mechanism remains unclear. Our study aims to explore the underlying mechanism\u2014the contribution of the\n MALAT1<\/jats:italic>\n \/miR\u201030b\u20105p\/BAFF axis activation in monocytes to NMOSD disease attacks and relapses resistant to rituximab therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To investigate immune dysregulation in NMOSD, we established clinical groups comprising peripheral blood mononuclear cells (PBMCs) and serum from NMOSD patients: onset cases (PBMCs:\n n<\/jats:italic>\n \u2009=\u200910; serum:\n n<\/jats:italic>\n \u2009=\u200923) and rituximab\u2010treated cases subdivided into remission (\n n<\/jats:italic>\n \u2009=\u200926) and rituximab\u2010refractory relapse (\n n<\/jats:italic>\n \u2009=\u200913), along with healthy controls (\n n<\/jats:italic>\n \u2009=\u200915). To profile the\n MALAT1<\/jats:italic>\n \/miR\u201030b\u20105p\/BAFF axis and inflammatory mediators, we quantified\n MALAT1<\/jats:italic>\n , miR\u201030b\u20105p, BAFF, and cytokine levels using qPCR, ELISA, and Western Blot and validated molecular interactions via dual\u2010luciferase reporter assays. To characterize cellular heterogeneity, single\u2010cell RNA sequencing (scRNA\u2010seq) was performed on PBMCs from two rituximab\u2010refractory relapsed NMOSD patients, two rituximab\u2010remission NMOSD patients, and two healthy controls. For mechanistic validation, THP\u20101 cells were transfected with\n MALAT1<\/jats:italic>\n overexpression constructs or miR\u201030b\u20105p mimics, followed by functional assessments to determine their roles in monocyte activation and cytokine production.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Significant activation of the\n MALAT1<\/jats:italic>\n \/miR\u201030b\u20105p\/BAFF axis was observed in NMOSD patients at disease onset compared to healthy controls. Moreover, this axis correlated with rituximab\u2010refractory NMOSD, featuring monocyte\u2010specific\n MALAT1<\/jats:italic>\n upregulation and elevated serum BAFF in rituximab\u2010refractory relapse patients. In THP\u20101 cells, the overexpression of\n MALAT1<\/jats:italic>\n downregulated miR\u201030b\u20105p, resulting in increased BAFF expression and pro\u2010inflammatory cytokines secretion (IL\u20101\u03b2, IL\u20108, TNF\u2010\u03b1), while also accelerating cell proliferation. Significantly, transfection with miR\u201030b\u20105p mimics reversed the\n MALAT1<\/jats:italic>\n \u2010driven upregulation of BAFF and pro\u2010inflammatory cytokines, supporting the\n MALAT1<\/jats:italic>\n \/miR\u201030b\u20105p\/BAFF axis as a regulatory circuit underlying inflammatory dysregulation in NMOSD.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n We identify the\n MALAT1<\/jats:italic>\n \/miR\u201030b\u20105p axis as a driver of NMOSD pathogenesis and rituximab\u2010refractory relapse. Upregulation of monocytic\n MALAT1<\/jats:italic>\n suppresses miR\u201030b\u20105p, leading to increased BAFF and pro\u2010inflammatory cytokines secretion, thereby promoting inflammatory responses. Targeting this pathway may offer therapeutic potential for relapse prevention.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cns.70973","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T08:30:10Z","timestamp":1780907410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Interaction Between\n MALAT1\/miR\u201030b\u20105p\/BAFF<\/i>\n Axis and Inflammatory Cytokines Underlies Rituximab\u2010Refractory\n NMOSD<\/scp>"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6449-9014","authenticated-orcid":false,"given":"Meiqun","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Fujian Institute of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"The First Clinical College of Fujian Medical University Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Fujian Institute of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Fujian Institute of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Department of Neurology Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Fujian Institute of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-2362","authenticated-orcid":false,"given":"Aiyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Fujian Institute of Neurology, The First Affiliated Hospital Fujian Medical University Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"issue":"12","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41582-021-00568-8","article-title":"Hope for Patients With Neuromyelitis Optica Spectrum Disorders\u2014From Mechanisms to Trials","volume":"17","author":"Pittock S. 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