{"id":991,"date":"2025-12-09T09:49:00","date_gmt":"2025-12-09T09:49:00","guid":{"rendered":"https:\/\/wickedsister.evit.com.au\/index.php\/2025\/12\/09\/cd20-depleters-know-one-know-them-all\/"},"modified":"2025-12-09T09:49:00","modified_gmt":"2025-12-09T09:49:00","slug":"cd20-depleters-know-one-know-them-all","status":"publish","type":"post","link":"https:\/\/wickedsister.evit.com.au\/index.php\/2025\/12\/09\/cd20-depleters-know-one-know-them-all\/","title":{"rendered":"CD20-depleters know one know them all?"},"content":{"rendered":"<div class=\"twitter-share\"><a href=\"https:\/\/twitter.com\/intent\/tweet?url=https%3A%2F%2Fmultiple-sclerosis-research.org%2F2025%2F12%2Fcd20-depleters-know-one-know-them-all%2F&#038;via=the_MSBlog\" class=\"twitter-share-button\" data-size=\"large\">Tweet<\/a><\/div>\n<p>The answer to the question above is no, but they all deplete B cells&#8230;this study looks at T and B cells after depletion with ublituximab and T cells drop transiently naive B cells show rapid and long term depletion.<\/p>\n<p>The depletion reproduced from paper below for CD8 T cells (left) <strong>AND B CELLS<\/strong> under creative common CC-BY. T cells are transiently reduced&#8230;so we think this is why ublituximab works or do you take the easier view that it has something to do with B cells.<\/p>\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"846\" height=\"269\" src=\"https:\/\/multiple-sclerosis-research.org\/wp-content\/uploads\/2025\/12\/image-3.png\" alt=\"\" class=\"wp-image-54641\" \/><\/figure>\n<p>In the blood naive cells make up about 60% of the cells and memory B cells about 30-35%. <em>In the methods there is no mention of subdivision of the CD19+ B cells and why they are naive B cells and not a mix of naive and memory B cells. <\/em><\/p>\n<p><em>However they have to say<\/em> &#8220;However, anti-CD20 therapies also target a small subset of CD20<sup>+<\/sup>&nbsp;T cells, which display heightened pro-inflammatory and CNS-migratory properties compared to CD20<sup>\u2212<\/sup>&nbsp;counterparts. Their selective and more durable depletion may partly explain early clinical effects and immune resetting.&#8221;&#8230;<\/p>\n<p>&nbsp;<\/p>\n<p>Zangh\u00ec A, Di Filippo PS, Papale M, Rutigliano C, Moretti MC, Avolio C, Corso G, D&#8217;Amico E. Modeling lymphocyte subset dynamics after ublituximab therapy in patients with multiple sclerosis: an Italian prospective study. Front Immunol. 2025 Nov 21;16:1688090.&nbsp;<\/p>\n<p><strong>Background and objectives:&nbsp;<\/strong>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<sup>+<\/sup>CD8<sup>+<\/sup>&nbsp;T cells and CD19<sup>+<\/sup>&nbsp;B naive cells, the two subsets that exhibited the most distinctive early kinetics.<\/p>\n<p><strong>Methods:&nbsp;<\/strong>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.<\/p>\n<p><strong>Results:&nbsp;<\/strong>A total cohort of 16 patients was enrolled, with a median age of 47 (Q1-Q3 41-58), 69% men, median EDSS of 4.5, and median body mass index (BMI) of 26.9 kg\/m<sup>2<\/sup>. Mixed-effects models showed a significant effect of time on all lymphocyte subsets. <strong>CD3<sup>+<\/sup>&nbsp;T cells decreased by 1,577 cells\/\u03bcL immediately after ublituximab infusion (<em>p<\/em>&nbsp;&lt; 0.001), returning to baseline from day 7 onward. CD3<sup>+<\/sup>CD8<sup>+<\/sup>&nbsp;T cells dropped by approximately 400 cells\/\u03bcL within the first week (day 7 = 44 cells\/\u03bcL; 95% CI 11-77) and stabilized from day 30. CD3<sup>+<\/sup>CD4<sup>+<\/sup>&nbsp;T cells fell by 1,133 cells\/\u03bcL post-infusion (<em>p<\/em>&nbsp;&lt; 0.001), but rebounded from day 7 and remained stable through day 180. <\/strong><em>CD19<sup>+<\/sup>&nbsp;naive B cells remained profoundly suppressed throughout the 6 months (all&nbsp;p&nbsp;&lt; 0.001)<\/em>. CD16<sup>+<\/sup>CD56<sup>+<\/sup>&nbsp;NK cells showed a transient reduction of 239 cells\/\u03bcL at day 0 (<em>p<\/em>&nbsp;= 0.004), normalizing by day 7. <em>Regression analyses at day 30 indicate no significant baseline predictors for CD3<sup>+<\/sup>CD8<sup>+<\/sup>&nbsp;T or CD19<sup>+<\/sup>&nbsp;naive B-cell recovery<\/em> (<em>R<\/em>\u00b2 = 0.48 and 0.24, all&nbsp;<em>p<\/em>&nbsp;&gt; 0.05). Infusion reactions were mild and self-limited; no adverse events occurred.<\/p>\n<p><strong>Discussion:&nbsp;<\/strong>In our cohort, ublituximab induced rapid, durable CD19<sup>+<\/sup>&nbsp;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.<\/p>\n<p><em>Source: <a href=\"https:\/\/multiple-sclerosis-research.org\/2025\/12\/cd20-depleters-know-one-know-them-all\/?utm_source=rss&#038;utm_medium=rss&#038;utm_campaign=cd20-depleters-know-one-know-them-all\" rel=\"nofollow noopener\" target=\"_blank\">multiple-sclerosis-research.org<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tweet The answer to the question above is no, but they all deplete B cells&#8230;this study looks at T and B cells after depletion with ublituximab and T cells drop transiently naive B cells show rapid and long term depletion. The depletion reproduced from paper below for CD8 T cells (left) AND B CELLS under&#8230;<\/p>\n","protected":false},"author":0,"featured_media":992,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[11,15,9,8,13,14,12,10],"class_list":["post-991","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-multiple-sclerosis-research","tag-brain-repair","tag-marburg-type-ms","tag-ms","tag-multiple-sclerosis","tag-myelin","tag-neuroregeneration","tag-oligodendrocyte","tag-remyelination"],"_links":{"self":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/991","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/comments?post=991"}],"version-history":[{"count":0,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/posts\/991\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media\/992"}],"wp:attachment":[{"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/media?parent=991"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/categories?post=991"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wickedsister.evit.com.au\/index.php\/wp-json\/wp\/v2\/tags?post=991"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}