ArticleThe Journal of clinical investigation2019
Membrane assembly of aquaporin-4 autoantibodies regulates classical complement activation in neuromyelitis optica.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 119 citations in OpenAlex.
- The cascade to pathogenicity in autoantibody-mediated CNS diseases.Brain : a journal of neurology · 2026Review
- The Comprehensive Live Cell-Based Cytotoxicity Assay for Monitoring Disease Activity and Guiding Rescue Therapy in Acute Attacks of NMOSD.Annals of clinical and translational neurology · 2026Article
- Complement C4d Informs the Differential Diagnosis of Inflammatory Demyelinating CNS Diseases.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Sjögren Syndrome Candidate Autoantigen AQP5 Triggers AQP4 CNS Autoimmunity Through Self-Antigen Mimicry.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Inflammatory transcriptomic signatures in a human cellular NMOSD model reveal upregulation of NF-κB and IL6 pathways.Scientific reports · 2025Article
- Human Cytomegalovirus Associated Neuropathies: A Comprehensive Review From Pathophysiology to Clinical and Therapeutic Considerations.Journal of the peripheral nervous system : JPNS · 2025Review
- Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis.Science advances · 2025Article
- Structural basis of aquaporin-4 autoantibody binding in neuromyelitis optica.Science advances · 2025Article
- AQP4-specific T cells determine lesion localization in the CNS in a model of NMOSD.Acta neuropathologica communications · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Induction of immune tolerance in NMOSD and MOGAD.Therapeutic advances in neurological disorders · 2025Review
- Targeting cytokine networks in neuroinflammatory diseases.Nature reviews. Drug discovery · 2024Review
- MOG CNS Autoimmunity and MOGAD.Neurology(R) neuroimmunology & neuroinflammation · 2024Review
- Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder.International journal of molecular sciences · 2024Article
- Moving towards a new era for the treatment of neuromyelitis optica spectrum disorders.Journal of neurology · 2024Review
- Structural Basis of Aquaporin-4 Autoantibody Binding in Neuromyelitis Optica.bioRxiv : the preprint server for biology · 2024Article
- The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. Super-resolution microscopy revealed that AQP4 rAbs with enhanced CDC preferentially formed organized clusters on supramolecular AQP4 orthogonal arrays, linking epitope-dependent multimeric assembly with enhanced C1q binding and activation. The resulting model of AQP4-IgG CDC provides a framework for understanding classical complement activation in human autoantibody-mediated disorders and identifies a potential new therapeutic avenue for treating NMO.
Indexed as
Identifiers
What OpenQuestion holds
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.