ArticleEBioMedicine2023
B cell depletion therapy does not resolve chronic active multiple sclerosis lesions.
Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Characterizing iron rim lesions in multiple sclerosis: a biomarker for disease activity and progression: a systematic review and meta-analysis.Neuroradiology · 2025Pooled it
- Reduced Paramagnetic Rim Visibility Signals Lesion Aging and Tissue Degeneration in Progressive Multiple Sclerosis: Impact on Clinical Trials.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Diffusion Basis Spectrum Imaging of Tissue Microstructure and Early Treatment in Multiple Sclerosis.Annals of clinical and translational neurology · 2026Article
- Article
- Targeting progressive multiple sclerosis: Toward mechanism-informed precision medicine.Journal of internal medicine · 2026Review
- Quantifying the Impact of Ocrelizumab on Paramagnetic Rim Lesions in Multiple Sclerosis.Annals of clinical and translational neurology · 2026Article
- Foamy microglia link oxylipins to disease progression in multiple sclerosis.Nature neuroscience · 2026Article
- Depression as a Disease of White Matter Network Disruption: Learning From Multiple Sclerosis.Biological psychiatry · 2026Review
- Treatment Effects on Chronic Active Lesions in Multiple Sclerosis: Current Evidence and Future Perspectives.Neurology and therapy · 2026Review
- The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.Acta neuropathologica · 2026Review
- Cell death in multiple sclerosis.Cell death and differentiation · 2026Review
- A HIF1A variant impacts long-term disability and smoldering inflammation in multiple sclerosis.Acta neuropathologica · 2026Article
- Ocrelizumab Discontinuation vs. Continuation After Safety Events: Comparative Insights from MSBase.Current neuropharmacology · 2026Article
- Smoldering neuroinflammation in progressive multiple sclerosis: mechanisms, imaging biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Neurovascular dysfunction in the development and progression of neuroinflammatory diseases.Frontiers in cellular neuroscience · 2026Review
- Unveiling a silent threat: slowly expanding spinal cord lesion linked to clinical worsening in multiple sclerosis: a case report.Journal of neurology · 2025Article
- Spatially-restricted inflammation-induced senescent-like glia in multiple sclerosis and patient-derived organoids.Nature communications · 2025Article
- Maintenance of chronic neuroinflammation in multiple sclerosis via interferon signaling and CD8 T-cell-mediated cytotoxicity.Research square · 2025Article
- Tolebrutinib Phase 2b Long-Term Extension Study: Two-Year Safety, MRI, and Clinical Efficacy Outcomes in Patients With Relapsing Multiple Sclerosis Patients.Neurology open access · 2025Article
- Perturbances in Both Circulating B and CD4European journal of immunology · 2025Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundChronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS.
methodsWe analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene-regulatory-network machine-learning analysis. Motivated by the results, we performed in vivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over ∼2 years.
findingsAlthough only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. In vivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with ≥4 PRL (p = 0.027).
interpretationDespite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of B-cells, inefficient passage of anti-CD20 antibodies across the blood-brain-barrier, and a paucity of B-cells in CAL could explain our findings.
fundingIntramural Research Program of NINDS, NIH; NINDS grants R01NS082347 and R01NS082347; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award (grant #1750327); Fund for Scientific Research (FNRS).
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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.