{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:06:31Z","timestamp":1788890791457,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007195","name":"Universit\u00e0 degli Studi di Napoli Federico II","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007195","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anti-CD20 monoclonal antibodies, such as ofatumumab, have significantly improved the management of multiple sclerosis (MS). Still, their long-term immunological effects, particularly on non-B-cell populations, remain poorly explored. We characterized longitudinal changes in circulating lymphocyte subsets and explored their clinical correlates in people with MS treated with ofatumumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted an observational cohort study including adults with MS who initiated ofatumumab and had paired baseline and on\u2011treatment assessments after at least 2\u00a0years (\n                      <jats:italic>n<\/jats:italic>\n                      =34). Immunophenotyping quantified total lymphocytes and subsets (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD20+, CD56+, CD27+, CD27+CD3+, CD27+CD19+, CD3+CD20\u2009+). Longitudinal change was modeled with linear mixed\u2011effects regression (fixed effects: age, sex, follow\u2011up duration, comorbidities, BMI, previous DMT; random intercept for subject). Annualized percentage change of each laboratory measure was related to relapses, MRI activity, EDSS progression, NEDA\u20113, and EDSS improvement using multivariable logistic regression with the same covariates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over approximately 2\u00a0years of treatment, we observed increased total lymphocytes (Coeff 251.47; 95% CI 29.29\u2013473.64;\n                      <jats:italic>p<\/jats:italic>\n                      =0.027), CD3+ (368.79; 183.66\u2013553.91;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), CD3+CD4+ (239.82; 107.32\u2013372.33;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), CD3+CD8+ (132.36; 52.92\u2013211.80;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), CD27+ (275.37; 124.11\u2013426.63;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), and CD27+CD3+ lymphocytes (451.99; 300.40\u2013603.58;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), and decreased CD19+ (\u2212\u2009181.55; \u2212234.40 to \u2212128.70;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), CD20+ (\u2212\u2009181.55; \u2212234.40 to \u2212128.70;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), and CD27+CD19+ lymphocytes (\u2212\u20091.82; \u22122.74 to \u22120.91;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01). No significant associations emerged between changes of lymphocytes and relapses, MRI activity, EDSS progression, NEDA\u20113, or EDSS improvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this exploratory, descriptive, real-world cohort, ofatumumab was associated with sustained B-cell depletion (CD19+\/CD20\u2009+) and parallel increases in broad T-cell compartments. No associations with clinical or MRI outcomes were detected; these negative findings should be interpreted cautiously within the hypothesis-generating design, given the small sample size and low frequency of disease-activity events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14088-2","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:06:47Z","timestamp":1788887207000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ofatumumab in multiple sclerosis: 2-year immune profiling and clinical correlates"],"prefix":"10.1007","volume":"273","author":[{"given":"Antonio","family":"Esposito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Corsaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria Delle","family":"Cave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Capasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Corsini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Matrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Cerbone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Petracca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Carotenuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lanzillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Castaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Brescia","family":"Morra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-3090","authenticated-orcid":false,"given":"Marcello","family":"Moccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"14088_CR1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1056\/NEJMra1401483","volume":"378","author":"DS Reich","year":"2018","unstructured":"Reich DS, Lucchinetti CF, Calabresi PA (2018) Multiple sclerosis. N Engl J Med 378:169\u2013180","journal-title":"N Engl J Med"},{"key":"14088_CR2","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/S1474-4422(21)00063-6","volume":"20","author":"A Bar-Or","year":"2021","unstructured":"Bar-Or A, Li R (2021) Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances. Lancet Neurol 20:470\u2013483. https:\/\/doi.org\/10.1016\/S1474-4422(21)00063-6","journal-title":"Lancet Neurol"},{"key":"14088_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/brainsci10100758","volume":"10","author":"D Florou","year":"2020","unstructured":"Florou D, Katsara M, Feehan J, Dardiotis E, Apostolopoulos V (2020) Anti-cd20 agents for multiple sclerosis: spotlight on ocrelizumab and ofatumumab. Brain Sci 10:1\u201313. https:\/\/doi.org\/10.3390\/brainsci10100758","journal-title":"Brain Sci"},{"key":"14088_CR4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1915309116","author":"JJ Sabatino","year":"2015","unstructured":"Sabatino JJ et al (2015) Anti-CD20 therapy depletes activated myelin-specific CD8 + T cells in multiple sclerosis. Proc Nat Acad Sci. https:\/\/doi.org\/10.1073\/pnas.1915309116","journal-title":"Proc Nat Acad Sci"},{"key":"14088_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1158487","author":"CC Fong","year":"2023","unstructured":"Fong CC, Spencer J, Howlett-Prieto Q, Feng X, Reder AT (2023) Adaptive and innate immune responses in multiple sclerosis with anti-CD20 therapy: gene expression and protein profiles. Front Neurol. https:\/\/doi.org\/10.3389\/fneur.2023.1158487","journal-title":"Front Neurol"},{"key":"14088_CR6","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1056\/NEJMoa1917246","volume":"383","author":"SL Hauser","year":"2020","unstructured":"Hauser SL et al (2020) Ofatumumab versus teriflunomide in multiple sclerosis. N Engl J Med 383:546\u2013557","journal-title":"N Engl J Med"},{"key":"14088_CR7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4161\/mabs.22771","volume":"5","author":"C Klein","year":"2013","unstructured":"Klein C et al (2013) Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs 5:22\u201333","journal-title":"MAbs"},{"key":"14088_CR8","doi-asserted-by":"crossref","unstructured":"Lin TS (2010) Pharmacogenomics and Personalized Medicine Ofatumumab: A Novel Monoclonal Anti-CD20 Antibody. Pharmacogenomics and Personalized Medicine, www.dovepress.com","DOI":"10.2147\/PGPM.S6840"},{"key":"14088_CR9","doi-asserted-by":"publisher","DOI":"10.1177\/11795735241249644","author":"C Friedli","year":"2024","unstructured":"Friedli C et al (2024) Different lymphocyte counts of multiple sclerosis patients treated with ofatumumab and ocrelizumab: a retrospective observational study. J Cent Nerv Syst Dis. https:\/\/doi.org\/10.1177\/11795735241249644","journal-title":"J Cent Nerv Syst Dis"},{"key":"14088_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107442","author":"A Moregola","year":"2024","unstructured":"Moregola A et al (2024) Profiling the impact of anti-human CD20 monoclonal antibodies on lymphocyte B cell subsets and their precursors in the bone marrow and in lymphoid tissues in an immunocompromised mouse engrafted with human cells. Pharmacol Res. https:\/\/doi.org\/10.1016\/j.phrs.2024.107442","journal-title":"Pharmacol Res"},{"key":"14088_CR11","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s40120-023-00518-0","volume":"12","author":"SL Hauser","year":"2023","unstructured":"Hauser SL et al (2023) The development of ofatumumab, a fully human Anti-CD20 monoclonal antibody for practical use in relapsing multiple sclerosis treatment. Neurol Ther 12:1491\u20131515. https:\/\/doi.org\/10.1007\/s40120-023-00518-0","journal-title":"Neurol Ther"},{"key":"14088_CR12","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3325\/cmj.2019.60.87","volume":"60","author":"R Milo","year":"2019","unstructured":"Milo R (2019) Therapies for multiple sclerosis targeting B cells. Croatian Med J 60:87\u201398","journal-title":"Croatian Med J"},{"key":"14088_CR13","unstructured":"Lisby S et al (2014) Per S Safety and Efficacy of Ofatumumab in Relapsing-Remitting Multiple Sclerosis A Phase 2 Study. www.neurology.org"},{"key":"14088_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.105886","author":"FF Konen","year":"2024","unstructured":"Konen FF et al (2024) Rapid depletion of CD20+ B and T cells following ofatumumab therapy onset. Mult Scler Relat Disord. https:\/\/doi.org\/10.1016\/j.msard.2024.105886","journal-title":"Mult Scler Relat Disord"},{"key":"14088_CR15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.clim.2006.08.016","volume":"122","author":"T Vallerskog","year":"2007","unstructured":"Vallerskog T et al (2007) Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol 122:62\u201374","journal-title":"Clin Immunol"},{"key":"14088_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/cells14070552","author":"AG Willison","year":"2025","unstructured":"Willison AG et al (2025) Effects of anti-CD20 antibody therapy on immune cell dynamics in relapsing-remitting multiple sclerosis. Cells. https:\/\/doi.org\/10.3390\/cells14070552","journal-title":"Cells"},{"key":"14088_CR17","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200004","author":"MR Von Essen","year":"2022","unstructured":"Von Essen MR et al (2022) Ofatumumab modulates inflammatory T cell responses and migratory potential in patients with multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. https:\/\/doi.org\/10.1212\/NXI.0000000000200004","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"14088_CR18","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1177\/13524585231195346","volume":"29","author":"SL Hauser","year":"2023","unstructured":"Hauser SL et al (2023) Efficacy and safety of four-year ofatumumab treatment in relapsing multiple sclerosis: the ALITHIOS open-label extension. Mult Scler J 29:1452\u20131464","journal-title":"Mult Scler J"},{"key":"14088_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.103431","author":"AL Spiezia","year":"2022","unstructured":"Spiezia AL et al (2022) Changes in lymphocytes, neutrophils and immunoglobulins in year-1 cladribine treatment in multiple sclerosis. Mult Scler Relat Dis. https:\/\/doi.org\/10.1016\/j.msard.2021.103431","journal-title":"Mult Scler Relat Dis"},{"key":"14088_CR20","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1007\/s00415-022-11350-1","volume":"270","author":"N Capasso","year":"2023","unstructured":"Capasso N et al (2023) Ocrelizumab effect on humoral and cellular immunity in multiple sclerosis and its clinical correlates: a 3-year observational study. J Neurol 270:272\u2013282","journal-title":"J Neurol"},{"key":"14088_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.814064","author":"JB Torres","year":"2022","unstructured":"Torres JB et al (2022) Distribution and efficacy of ofatumumab and ocrelizumab in humanized CD20 mice following subcutaneous or intravenous administration. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2022.814064","journal-title":"Front Immunol"},{"key":"14088_CR22","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.jneuroim.2019.04.017","volume":"332","author":"AE Lovett-Racke","year":"2019","unstructured":"Lovett-Racke AE et al (2019) B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients. J Neuroimmunol 332:187\u2013197","journal-title":"J Neuroimmunol"},{"issue":"1","key":"14088_CR23","doi-asserted-by":"publisher","first-page":"101351","DOI":"10.1016\/j.xcrm.2023.101351","volume":"5","author":"C Ulutekin","year":"2024","unstructured":"Ulutekin C, Galli E et al (2024) B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis. Cell Rep Med 5(1):101351. https:\/\/doi.org\/10.1016\/j.xcrm.2023.101351","journal-title":"Cell Rep Med"},{"key":"14088_CR24","doi-asserted-by":"publisher","DOI":"10.1177\/20552173251409954","author":"M Tanaka","year":"2026","unstructured":"Tanaka M, Kinoshita M, Tanaka K (2026) T lymphopenia in multiple sclerosis patients treated with ofatumumab: even with consideration for CD3+CD20+cells. Mult Scler J Exp Transl Clin. https:\/\/doi.org\/10.1177\/20552173251409954","journal-title":"Mult Scler J Exp Transl Clin"},{"key":"14088_CR25","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1002\/acn3.70042","volume":"12","author":"S Yang","year":"2025","unstructured":"Yang S et al (2025) Reconstitution of CXCR3+ CCR6+ Th17.1-like T cells in response to ofatumumab therapy in patients with multiple sclerosis. Ann Clin Transl Neurol 12:1043\u20131053","journal-title":"Ann Clin Transl Neurol"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-14088-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-14088-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-14088-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:06:49Z","timestamp":1788887209000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-14088-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":25,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["14088"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-14088-2","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"assertion":[{"value":"4 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Authors declare no potential conflict of interest in relation to this manuscript.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Data are available upon reasonable request to the corresponding author.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"579"}}