{"doi":"10.3389/fimmu.2025.1590165","title":"B cell-extrinsic and intrinsic factors linked to early immune repletion after anti-CD20 therapy in patients with multiple sclerosis of African ancestry","abstract":"Introduction: 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. Methods: 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. Results: 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. Discussion: 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.","journal":"Frontiers in Immunology","year":2025,"id":567905,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1472435,"name":"Abhimanyu N. Amarnani","orcid":null,"position":1,"is_corresponding":false},{"id":1472436,"name":"Arnaldo A. Arbini","orcid":null,"position":2,"is_corresponding":false},{"id":275469,"name":"Angie Kim","orcid":"0000-0001-6770-0616","position":3,"is_corresponding":false},{"id":1472437,"name":"Hannah Kopinsky","orcid":null,"position":4,"is_corresponding":false},{"id":2222,"name":"David Fenyö","orcid":"0000-0001-5049-3825","position":5,"is_corresponding":false},{"id":529976,"name":"Ilya Kister","orcid":"0000-0003-3549-949X","position":6,"is_corresponding":false},{"id":447495,"name":"Gregg J. Silverman","orcid":"0000-0001-9480-9457","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:48.183032Z","pmid":"40557147","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}