{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:27:49Z","timestamp":1785457669439,"version":"3.56.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"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 Introduction<\/jats:title>\n Recent investigations have identified patients of African ancestry (AA) with Multiple Sclerosis (MS), who display more rapid B-cell repopulation after standard semi-annual infusions with an anti-CD20 monoclonal antibody for B cell depletion. In this study, we explored the immunologic and genetic factors, with serum drug monitoring, that may contribute to a faster rate of B-cell repletion that follows during recovery from treatment with anti-CD20 antibody.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In AA MS patients treated with an anti-CD20 antibody that had early repopulation of peripheral blood B cells, we assessed for extrinsic factors, including the presence of anti-drug antibodies against ocrelizumab, which may contribute to early repletion. We also documented the associated serum drug levels. In addition, we examined for inheritance of intrinsic gene polymorphisms associated with B cell survival and immune function.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Our findings identified a subset of AA patients with early B cell repletion after anti-CD20 treatment associated with anti-drug antibodies and an absence of detectable drug. Furthermore, a separate set of AA patients with the early B cell repletion phenotype without anti-drug antibodies had significant over-representation of genetic polymorphisms that map to genes for the B cell survival factor, BAFF, to antibody-dependent cytotoxicity, and to pathways involved in inflammation, leukocyte activation and B cell differentiation.<\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n In AA patients with MS, after anti-CD20 antibody treatment we found an unexpected high occurrence of early B cell replenishment. This was associated with the presence of anti-drug antibodies and\/or specific genetic polymorphisms. Larger studies are now needed to determine whether these factors may lead to impaired therapeutic benefits of B cell targeted therapy and clinical progression, and these findings may be useful to guide future optimized personalized therapeutic strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1590165","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T01:23:00Z","timestamp":1749518580000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["B cell-extrinsic and intrinsic factors linked to early immune repletion after anti-CD20 therapy in patients with multiple sclerosis of African ancestry"],"prefix":"10.3389","volume":"16","author":[{"given":"Gregg J.","family":"Silverman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhimanyu N.","family":"Amarnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo A.","family":"Arbini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Kopinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fenyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Kister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.021","article-title":"Multiple sclerosis: mechanisms and immunotherapy","volume":"97","author":"Baecher-Allan","year":"2018","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41590-018-0135-x","article-title":"Reassessing B cell contributions in multiple sclerosis","volume":"19","author":"Li","year":"2018","journal-title":"Nat Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI177793","article-title":"A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations","volume":"135","author":"Cantoni","year":"2025","journal-title":"J Clin Invest"},{"key":"B5","doi-asserted-by":"publisher","first-page":"24319302","DOI":"10.1101\/2025.01.02.24319302","article-title":"Comprehensive cerebrospinal fluid analysis indicates key roles for B cells in multiple sclerosis","author":"Fernandez Zapata","year":"2025","journal-title":"medRxiv"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"New Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10744-x","article-title":"Anti-CD20 therapies for multiple sclerosis: current status and future perspectives","volume":"269","author":"Margoni","year":"2022","journal-title":"J Neurol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1001\/jamaneurol.2023.1135","article-title":"Population-based estimates for the prevalence of multiple sclerosis in the United States by race, ethnicity, age, sex, and geographic region","volume":"80","author":"Hittle","year":"2023","journal-title":"JAMA Neurol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182918cc2","article-title":"Incidence of multiple sclerosis in multiple racial and ethnic groups","volume":"80","author":"Langer-Gould","year":"2013","journal-title":"Neurology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0000000000000112","article-title":"Multiple sclerosis in US minority populations: clinical practice insights","volume":"5","author":"Khan","year":"2015","journal-title":"Neurol: Clin Pract"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2741\/2222","article-title":"Anti-CD20 therapy and autoimmune disease: therapeutic opportunities and evolving insights","volume":"12","author":"Silverman","year":"2007","journal-title":"Front Biosci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"103830","DOI":"10.1016\/j.msard.2022.103830","article-title":"Faster B-cell repletion after anti-CD20 infusion in Black patients compared to white patients with neurologic diseases","volume":"63","author":"Saidenberg","year":"2022"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad347","article-title":"g: Profiler\u2014interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)","volume":"51","author":"Kolberg","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01234-0","article-title":"RNA-sequencing data-driven dissection of human plasma cell diferentiation reveals new potential transcription regulators","volume":"35","author":"Kassambara","year":"2021"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1004077","article-title":"GenomicScape: an easy-to-use web tool for gene expression data analysis. Application to investigate the molecular events in the diferentiation of B cells into plasma cells","volume":"11","author":"Kassambara","year":"2015","journal-title":"PloS Comput Biol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"6843","DOI":"10.1038\/s41467-021-27232-5","article-title":"Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation","volume":"12","author":"Lee","year":"2021","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.1038\/s41467-023-40621-2","article-title":"An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells","volume":"14","author":"Salerno","year":"2023","journal-title":"Nat Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"101422","DOI":"10.1016\/j.msard.2019.101422","article-title":"TNFRSF13C\/BAFFR P21R and H159Y polymorphisms in multiple sclerosis","volume":"37","author":"Ntellas","year":"2020","journal-title":"Multi Sclerosis Related Disord"},{"key":"B20","doi-asserted-by":"publisher","first-page":"123303","DOI":"10.1016\/j.jns.2024.123303","article-title":"Multi-Omic characterization of the effects of ocrelizumab in patients with relapsing-remitting multiple sclerosis","volume":"467","author":"Kornilov","year":"2024","journal-title":"J Neurol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3024","article-title":"The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program","volume":"15","author":"Itoh-Nakadai","year":"2014","journal-title":"Nat Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv078","article-title":"An ImmunoChip study of multiple sclerosis risk in African Americans","volume":"138","author":"Isobe","year":"2015"},{"key":"B23","article-title":"Towards a network theory of the immune system","author":"Jerne","year":"1974","journal-title":"Ann Immunol (Inst. Pasteur), C, (Paris)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2014.10.003","article-title":"The idiotypic network in the regulation of autoimmunity: Theoretical and experimental studies","volume":"375","author":"Menshikov","year":"2015","journal-title":"J Theor Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300156","article-title":"VH2+ Antigen-experienced B cells in the cerebrospinal fluid are expanded and enriched in pediatric anti-NMDA receptor encephalitis","volume":"211","author":"Monson","year":"2023","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.680581","article-title":"The role of B cells in primary progressive multiple sclerosis","volume":"12","author":"Holloman","year":"2021","journal-title":"Front Neurol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1172993","article-title":"Understanding humoral immunity and multiple sclerosis severity in Black, and Latinx patients","volume":"14","author":"Telesford","year":"2023","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"105047","DOI":"10.1016\/j.msard.2023.105047","article-title":"African American patients with Multiple Sclerosis (MS) have higher proportions of CD19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients","volume":"79","author":"Xue","year":"2023","journal-title":"J Multiple Sclerosis and Related Disorders"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/217961","article-title":"Oligoclonal bands in cerebrospinal fluid of black patients with multiple sclerosis","volume":"2015","author":"da Gama","year":"2015","journal-title":"BioMed Res Int"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.87310","article-title":"B cells from African American lupus patients exhibit an activated phenotype","volume":"1","author":"Menard","year":"2016","journal-title":"JCI Insight"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610528","article-title":"Overexpression of the Cytokine BAFF and Autoimmunity Risk","volume":"376","author":"Steri","year":"2017","journal-title":"N Engl J Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/art.30598","article-title":"B lymphocyte stimulator levels in systemic lupus erythematosus: higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels","volume":"63","author":"Ritterhouse","year":"2011","journal-title":"Arthritis Rheum"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/BF00916817","article-title":"The influence of age, race, and gender on peripheral blood mononuclear-cell subsets in healthy nonsmokers","volume":"9","author":"Tollerud","year":"1989","journal-title":"J Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11704","article-title":"Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct pre-vaccination gene expression profiles in blood","volume":"7","author":"Kurupati","year":"2016","journal-title":"Oncotarget"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005360","article-title":"Common gene variants in the tumor necrosis factor (TNF) and TNF receptor superfamilies and NF-kB transcription factors and non-Hodgkin lymphoma risk","volume":"4","author":"Wang","year":"2009","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.7938","article-title":"Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders","volume":"24","author":"Novak","year":"2006","journal-title":"J Clin Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00950-2","article-title":"The pharmacogenetics of rituximab: Potential implications for anti-CD20 therapies in multiple sclerosis","volume":"17","author":"Zhong","year":"2020","journal-title":"Neurotherapeutics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1276","article-title":"Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab","volume":"72","author":"Kim","year":"2015","journal-title":"JAMA Neurol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105851","DOI":"10.1016\/j.msard.2024.105851","article-title":"A personalized approach for anti-CD20 therapies in multiple sclerosis","volume":"91","author":"Hogenboom","year":"2024","journal-title":"Multi Sclerosis Related Disord"},{"key":"B40","doi-asserted-by":"publisher","first-page":"105028","DOI":"10.1016\/j.msard.2023.105028","article-title":"Ocrelizumab B-cell repopulation-guided extended interval dosing versus standard dosing\u2013similar clinical eficacy with decreased immunoglobulin M deficiency rates","volume":"79","author":"Rempe","year":"2023","journal-title":"Multi Sclerosis Related Disord"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1177\/13524585231208311","article-title":"Extended interval dosing of ocrelizumab in patients with multiple sclerosis is not associated with meaningful differences in disease activity","volume":"30","author":"Bou Rjeily","year":"2024","journal-title":"Multi Sclerosis J"},{"key":"B42","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s12974-023-02900-z","article-title":"Extended interval dosing of ocrelizumab modifies the repopulation of B cells without altering the clinical efficacy in multiple sclerosis","volume":"20","author":"Rodriguez-Mogeda","year":"2023","journal-title":"J neuroinflamm"},{"key":"B43","doi-asserted-by":"publisher","first-page":"106257","DOI":"10.1016\/j.msard.2025.106257","article-title":"Comparing the efficacy and safety of extended vs standard dosing of ocrelizumab in MS: A systemic review and meta-analysis","author":"Baig","year":"2025","journal-title":"Multi Sclerosis Related Disord"},{"key":"B44","doi-asserted-by":"publisher","first-page":"868","DOI":"10.3390\/jcm10040868","article-title":"Assessment of disability progression independent of relapse and brain MRI activity in patients with multiple sclerosis in Poland","volume":"10","author":"Kapica-Topczewska","year":"2021","journal-title":"J Clin Med"},{"key":"B45","first-page":"13524585251329849","article-title":"Suboptimal B-cell depletion is associated with progression independent of relapse activity in multiple sclerosis patients treated with ocrelizumab","author":"Revie","year":"2024","journal-title":"Multi Sclerosis J"},{"key":"B46","article-title":"Multiple sclerosis in the Black population of the United States","volume":"4","author":"Brayo","year":"2021","journal-title":"Pract Neurol"}],"updated-by":[{"DOI":"10.3389\/fimmu.2025.1649409","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1590165\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:36:14Z","timestamp":1753173374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1590165\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2025.1590165"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1590165","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.05.25321882","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]},"article-number":"1590165"}}