ArticleAnnals of clinical and translational neurology2025
Durable B-Cell Impairment While Sparing IgA B Cells After Ocrelizumab Therapy in Multiple Sclerosis.
Article in Annals of clinical and translational neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03085810 (An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis), which is not on this map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis
Who cites it
3 citing papers in PubMed.
- IgA autoantibodies demonstrate a novel mechanism of MuSK myasthenia gravis pathology.Brain : a journal of neurology · 2026Article
- Multiplex Detection of Immunoglobulins Uncovers Intrathecal IgA Elevation in Multiple Sclerosis.Cells · 2026Article
- Persistent Classical and Atypical Memory B Cells Underlie Heterogeneous Vaccine Responses in Ocrelizumab-Treated Multiple Sclerosis.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
objectivesOcrelizumab (OCR), a humanized anti-CD20 monoclonal antibody, is highly efficient in relapsing-remitting multiple sclerosis (RR-MS). We assessed early cellular B-cell profiles in patients prior to OCR treatment, on OCR treatment, and after 15 months of therapy discontinuation. This study aims to provide new clues about the mechanisms of action of OCR and about disease pathophysiology.
methodsPatients with early, treatment-naive, RR-MS were included from 11 centers participating in an ancillary study of the ENSEMBLE trial (NCT03085810) to evaluate the effectiveness and safety of OCR. The phenotypic B-cell immune profile was comprehensively assessed in 18 patients by spectral flow cytometry at baseline, after 1 year of OCR treatment, and compared with 10 healthy volunteers (HVs) (matched for age and sex) on cryopreserved peripheral blood mononuclear cells (PBMC). We also analyzed B-cell reconstitution after a median time of 15 months after trial withdrawal in three patients by flow cytometry and single-cell RNA sequencing.
resultsUsing spectral flow cytometry we defined the proportions and absolute numbers of naive, transitional, Ig-G, Ig-A, Ig-M memory B cells, Ig-G, Ig-A, Ig-M plasmablasts, and plasma cells. At baseline we found an increased frequency of IgG-secreting B cells in MS patients compared to HV. During OCR treatment, the proportion of the different subsets of B cells was strongly modified. In the mature clusters, we observed that the treatment partially spared memory IgA B cells. In parallel, we observed that differentiated IgA plasmablasts and plasma cells were more increased than the other differentiated clusters. Interestingly, in the three patients who stopped the treatment single-cell RNA sequencing showed that the B cells that reappeared were mainly naive with an inflammatory and migratory phenotype concomitantly to a rise of regulatory B cells. DISCUSSION: Our findings support an increased regulatory phenotype of remaining B cells under treatment with OCR and replenishment of undifferentiated B cells accumulating features of inflammatory and migratory patterns after OCR discontinuation, counterbalanced by an increased proportion of regulatory B cells.
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