ArticleScience translational medicine2021
Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 78 citations in OpenAlex.
- Safety and efficacy of daratumumab in immune thrombocytopenia.Blood advances · 2026Trial
- Variant-specific spike conformational dynamics shape memory B cell selection during recall.bioRxiv : the preprint server for biology · 2026Article
- Lymph node microenvironment remodeling unlocks local antibody-mediated B cell depletion.Science advances · 2026Article
- IgA autoantibodies demonstrate a novel mechanism of MuSK myasthenia gravis pathology.Brain : a journal of neurology · 2026Article
- Research Advances in Rituximab-Resistant Membranous Nephropathy.Kidney medicine · 2026Review
- Synergistic Interaction Between MALAT1/miR-30b-5p/BAFF Axis and Inflammatory Cytokines Underlies Rituximab-Refractory NMOSD.CNS neuroscience & therapeutics · 2026Article
- Affinity-matured B cell responses neutralizing type-I interferons underlie severe viral infections.Cell · 2026Article
- Identification and characterization of bone marrow plasma cells producing IFN-γ-neutralizing autoantibodies in adult-onset immunodeficiency.Cell reports. Medicine · 2026Article
- Biomimetic vesicles engineered from modified tumour cells act as personalized vaccines for post-surgical cancer immunotherapy.Nature nanotechnology · 2026Article
- Daratumumab for Treatment of Refractory Podocytopathy: A Case Report.Kidney medicine · 2026Article
- CD40L and IL-4 lymph node-associated signals protect B cells from rituximab-induced ADCC via KIR and NKG2A.Clinical and experimental immunology · 2026Article
- Treatment strategies for rituximab-resistant primary membranous nephropathy: from resistance mechanisms to emerging therapies.Frontiers in immunology · 2026Review
- Sequential efgartigimod and ofatumumab for stiff-person syndrome: a case report illustrating a pathophysiology-informed strategy and literature review.Frontiers in immunology · 2026Review
- Revisiting B-cell targeted therapies in rheumatoid arthritis: from paradoxical biology to deep immune reset.Frontiers in immunology · 2026Review
- Clinical heterogeneity and treatment optimization in anti-KLHL11 encephalitis: two case reports and literature review.Frontiers in immunology · 2026Review
- Research progress on chimeric antigen receptor-based immunotherapy against autoimmune diseases.Human vaccines & immunotherapeutics · 2025Review
- Differences in Dynamics of Specific Antinuclear Antibodies and Their Susceptibility to B Cell-Targeting Treatment in Patients With Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Review
- IgA class-switched CD27-CD21+ B cells in IgA nephropathy.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Relapse-free survival is progressively shortened in a subset of Black patients with immune-mediated TTP treated in the rituximab era.Blood advances · 2025Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
Abstract
Rituximab (RTX), an antibody targeting CD20, is widely used as a first-line therapeutic strategy in B cell-mediated autoimmune diseases. However, a large proportion of patients either do not respond to the treatment or relapse during B cell reconstitution. Here, we characterize the cellular basis responsible for disease relapse in secondary lymphoid organs in humans, taking advantage of the opportunity offered by therapeutic splenectomy in patients with relapsing immune thrombocytopenia. By analyzing the B and plasma cell immunoglobulin gene repertoire at bulk and antigen-specific single-cell level, we demonstrate that relapses are associated with two responses coexisting in germinal centers and involving preexisting mutated memory B cells that survived RTX treatment and naive B cells generated upon reconstitution of the B cell compartment. To identify distinctive characteristics of the memory B cells that escaped RTX-mediated depletion, we analyzed RTX refractory patients who did not respond to treatment at the time of B cell depletion. We identified, by single-cell RNA sequencing (scRNA-seq) analysis, a population of quiescent splenic memory B cells that present a unique, yet reversible, RTX-shaped phenotype characterized by down-modulation of B cell-specific factors and expression of prosurvival genes. Our results clearly demonstrate that these RTX-resistant autoreactive memory B cells reactivate as RTX is cleared and give rise to plasma cells and further germinal center reactions. Their continued surface expression of CD19 makes them efficient targets for current anti-CD19 therapies. This study thus identifies a pathogenic contributor to autoimmune diseases that can be targeted by available therapeutic agents.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.