ArticleProceedings of the National Academy of Sciences of the United States of America2022
Rituximab abrogates aquaporin-4-specific germinal center activity in patients with neuromyelitis optica spectrum disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Clinical phenotype and outcomes in autoimmune encephalitis after herpes simplex virus encephalitis: A systematic review and meta-analysis.The Journal of infection · 2025Pooled it
- B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity.Annals of clinical and translational neurology · 2024Trial
- The cascade to pathogenicity in autoantibody-mediated CNS diseases.Brain : a journal of neurology · 2026Review
- Safety and Efficacy of Obinutuzumab β (MIL62), a Novel Glycoengineered Type II Anti-CD20 Monoclonal Antibody, in Patients with Neuromyelitis Optica Spectrum Disorder: A Multicenter, Single-Arm, Phase Ib Clinical Trial.Neurology and therapy · 2026Article
- Impact of Anti-CD20 Therapies on Cytokine, Chemokine and Adhesion Molecule Dynamics in Multiple Sclerosis: A Narrative Review.Neurology and therapy · 2026Review
- B Cells and B Cell Depletion in Autoimmunity and Atherosclerosis.Life (Basel, Switzerland) · 2026Review
- Intranodal expansion of follicular T helper cells in patients with multiple sclerosis.JCI insight · 2025Article
- Autoimmune encephalitis.Nature reviews. Disease primers · 2025Review
- Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant.Cell reports · 2025Article
- Rituximab Use for Relapse Prevention in Anti-NMDAR Antibody-Mediated Encephalitis: A Multicenter Cohort Study.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Emerging Role of Targeted Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Permissive central tolerance plus defective peripheral checkpoints license pathogenic memory B cells in CASPR2-antibody encephalitis.Science advances · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes.Brain : a journal of neurology · 2025Article
- Induction of immune tolerance in NMOSD and MOGAD.Therapeutic advances in neurological disorders · 2025Review
- Antibodies in neurological diseases: Established, emerging, explorative.Immunological reviews · 2024Review
- Multi-site Ultrasound-guided Fine Needle Aspiration to Study Cells and Soluble Factors From Human Lymph Nodes.Current protocols · 2024Article
- Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Fine needle aspiration of human lymph nodes reveals cell populations and soluble interactors pivotal to immunological priming.European journal of immunology · 2024Article
- The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.Brain : a journal of neurology · 2024Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
Abstract
Neuromyelitis optica spectrum disorders (NMOSDs) are caused by immunoglobulin G (IgG) autoantibodies directed against the water channel aquaporin-4 (AQP4). In NMOSDs, discrete clinical relapses lead to disability and are robustly prevented by the anti-CD20 therapeutic rituximab; however, its mechanism of action in autoantibody-mediated disorders remains poorly understood. We hypothesized that AQP4-IgG production in germinal centers (GCs) was a core feature of NMOSDs and could be terminated by rituximab. To investigate this directly, deep cervical lymph node (dCLN) aspirates (n = 36) and blood (n = 406) were studied in a total of 63 NMOSD patients. Clinical relapses were associated with AQP4-IgM generation or shifts in AQP4-IgG subclasses (odds ratio = 6.0; range of 3.3 to 10.8; P < 0.0001), features consistent with GC activity. From seven dCLN aspirates of patients not administered rituximab, AQP4-IgGs were detected alongside specific intranodal synthesis of AQP4-IgG. AQP4-reactive B cells were isolated from unmutated naive and mutated memory populations in both blood and dCLNs. After rituximab administration, fewer clinical relapses (annual relapse rate of 0.79 to 0; P < 0.001) were accompanied by marked reductions in both AQP4-IgG (fourfold; P = 0.004) and intranodal B cells (430-fold; P < 0.0001) from 11 dCLNs. Our findings implicate ongoing GC activity as a rituximab-sensitive driver of AQP4 antibody production. They may explain rituximab’s clinical efficacy in several autoantibody-mediated diseases and highlight the potential value of direct GC measurements across autoimmune conditions.
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Registered trials
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.