{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:35:11Z","timestamp":1790253311801,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background and objectives<\/jats:title>\n \n Ublituximab, a novel, glycoengineered anti-CD20 monoclonal antibody, has recently entered clinical use for multiple sclerosis (MS). In this study, we aimed to delineate the longitudinal kinetics of circulating lymphocyte subsets over the first 6 months following ublituximab initiation. Secondarily, we aimed to investigate whether relevant baseline demographic and clinical characteristics predicted the residual counts at day 30 after infusion of CD3\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n T cells and CD19\n +<\/jats:sup>\n B naive cells, the two subsets that exhibited the most distinctive early kinetics.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A real-world prospective study was performed at the MS Center of Foggia, Italy. Inclusion criteria were patients with a diagnosis of relapsing MS who started ublituximab between 1 December 2024 and 31 May 2025. Longitudinal trajectories were modeled with subject-specific random-intercept linear mixed-effects models. To identify determinants of early residual depletion, linear regression models were built.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total cohort of 16 patients was enrolled, with a median age of 47 (Q1\u2013Q3 41\u201358), 69% men, median EDSS of 4.5, and median body mass index (BMI) of 26.9 kg\/m\n 2<\/jats:sup>\n . Mixed-effects models showed a significant effect of time on all lymphocyte subsets. CD3\n +<\/jats:sup>\n T cells decreased by 1,577 cells\/\u03bcL immediately after ublituximab infusion (\n p<\/jats:italic>\n &lt; 0.001), returning to baseline from day 7 onward. CD3\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n T cells dropped by approximately 400 cells\/\u03bcL within the first week (day 7 = 44 cells\/\u03bcL; 95% CI 11\u201377) and stabilized from day 30. CD3\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n T cells fell by 1,133 cells\/\u03bcL post-infusion (\n p<\/jats:italic>\n &lt; 0.001), but rebounded from day 7 and remained stable through day 180. CD19\n +<\/jats:sup>\n naive B cells remained profoundly suppressed throughout the 6 months (all\n p<\/jats:italic>\n &lt; 0.001). CD16\n +<\/jats:sup>\n CD56\n +<\/jats:sup>\n NK cells showed a transient reduction of 239 cells\/\u03bcL at day 0 (\n p<\/jats:italic>\n = 0.004), normalizing by day 7. Regression analyses at day 30 indicate no significant baseline predictors for CD3\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n T or CD19\n +<\/jats:sup>\n naive B-cell recovery (\n R<\/jats:italic>\n \u00b2 = 0.48 and 0.24, all\n p<\/jats:italic>\n &gt; 0.05). Infusion reactions were mild and self-limited; no adverse events occurred.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n In our cohort, ublituximab induced rapid, durable CD19\n +<\/jats:sup>\n naive B-cell depletion with only transient, reversible effects on other lymphocyte subsets and preserved immunoglobulin levels. This signature extends to older and high BMI patients, supporting ublituximab as a versatile therapeutic option across heterogeneous MS populations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1688090","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T14:15:28Z","timestamp":1763734528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Modeling lymphocyte subset dynamics after ublituximab therapy in patients with multiple sclerosis: an Italian prospective study"],"prefix":"10.3389","volume":"16","author":[{"given":"Aurora","family":"Zangh\u00ec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola Sofia","family":"Di 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