{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:50:03Z","timestamp":1791273003431,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171777"],"award-info":[{"award-number":["82171777"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["20JCJQJC00280"],"award-info":[{"award-number":["20JCJQJC00280"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Ofatumumab, a fully human anti\u2010CD20 monoclonal antibody, is effective in reducing relapses and disability progression in patients with multiple sclerosis. This study aimed to examine immune profile changes associated with ofatumumab in a prospective cohort of Chinese patients with relapsing\u2013remitting multiple sclerosis (RRMS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventeen RRMS patients were enrolled in this uncontrolled, prospective, observational cohort study (OMNISCIENCE study) and received regular subcutaneous ofatumumab treatments. Immune cell subsets were analyzed by single\u2010cell mass cytometry at baseline and 6\u2009months post\u2010treatment. Peripheral blood monoclonal cells (PBMCs) from a separate cohort of treatment\u2010naive RRMS patients were used for cytokine analysis through ex\u00a0vivo flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following ofatumumab treatment, B cells in peripheral blood remained depleted, with surviving cells predominantly consisting of antibody\u2010secreting cells and transitional B cells. Increased proportions of NK cells and myeloid cells, particularly HLA\u2010DR<jats:sup>hi<\/jats:sup> intermediate monocytes, were observed, and FOXP3 and CTLA\u20104 expression on CD4<jats:sup>+<\/jats:sup> T cells was upregulated. Notably, prior to the subsequent dose of ofatumumab, Th17.1\u2010like CXCR3<jats:sup>+<\/jats:sup>CCR6<jats:sup>+<\/jats:sup> memory CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell clusters increased significantly, with a transient CD20 expression rebound. In\u00a0vitro experiments further confirmed that ofatumumab reduced these Th17.1 cell subsets and related pro\u2010inflammatory cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings suggest that ofatumumab impacts interactions among pathogenic B cells, T cells, and myeloid cells, with Th17.1 cells emerging as a potential direct target within T cells. Persistent and regular infusions of ofatumumab appear necessary to sustain clinical efficacy.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT05414487<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.70042","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:24:37Z","timestamp":1743553477000},"page":"1043-1053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Reconstitution of <scp>CXCR3<\/scp><sup>+<\/sup><scp>CCR6<\/scp><sup>+<\/sup> Th17.1\u2010Like T Cells in Response to Ofatumumab Therapy in Patients With Multiple Sclerosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Shu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute, Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-9478","authenticated-orcid":false,"given":"Tian\u2010Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute, Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute, Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Neurological Institute, Tianjin Medical University General Hospital  Tianjin 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