ArticleAnnals of clinical and translational neurology2016
Compromised fidelity of B-cell tolerance checkpoints in AChR and MuSK myasthenia gravis.
Article in Annals of clinical and translational neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Pathogenic properties of myasthenia gravis AChR autoantibodies associate with clinical response to efgartigimod.Journal of neurology, neurosurgery, and psychiatry · 2026Trial
- Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- High-Affinity Human Germline and Mutated Autoantibodies Commonly Cross-React to Self-Antigens in 5 Subgroups of Autoimmune Encephalitis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Failure of early B cell tolerance and possible BCR signaling dysregulation underlie NF155-mediated autoimmune nodopathies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Clinical utility of human leukocyte antigen genotyping and immunoglobulin G4 autoantibody testing in autoimmune neurological diseases: A focused minireview.World journal of biological chemistry · 2026Review
- Myasthenia gravis: the future is here.The Journal of clinical investigation · 2024Review
- Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology.Acta neuropathologica · 2023Article
- Antibodies Against Glutamic Acid Decarboxylase 65 Are Locally Produced in the CSF and Arise During Affinity Maturation.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Immunotherapies in MuSK-positive Myasthenia Gravis; an IgG4 antibody-mediated disease.Frontiers in immunology · 2023Review
- Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy.Acta neuropathologica communications · 2022Article
- Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations.Journal of clinical medicine · 2021Review
- Single-cell approaches to investigate B cells and antibodies in autoimmune neurological disorders.Cellular & molecular immunology · 2021Review
- Short- and Long-Lived Autoantibody-Secreting Cells in Autoimmune Neurological Disorders.Frontiers in immunology · 2021Review
- Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis.The Journal of experimental medicine · 2020Article
- Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Presence of Survivin on B Cells from Myasthenia Gravis Patients and the Potential of an Antibody to a Modified Survivin Peptide to Alleviate Weakness in an Animal Model.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- The B cell immunobiology that underlies CNS autoantibody-mediated diseases.Nature reviews. Neurology · 2020Review
- Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies.Immunological reviews · 2019Review
- Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveMyasthenia gravis (MG) is an autoimmune condition in which neurotransmission is impaired by binding of autoantibodies to acetylcholine receptors (AChR) or, in a minority of patients, to muscle specific kinase (MuSK). There are differences in the dominant IgG subclass, pathogenic mechanisms, and treatment responses between the two MG subtypes (AChR or MuSK). The antibodies are thought to be T-cell dependent, but the mechanisms underlying their production are not well understood. One aspect not previously described is whether defects in central and peripheral tolerance checkpoints, which allow autoreactive B cells to accumulate in the naive repertoire, are found in both or either form of MG.
methodsAn established set of assays that measure the frequency of both polyreactive and autoreactive B cell receptors (BCR) in naive populations was applied to specimens collected from patients with either AChR or MuSK MG and healthy controls. Radioimmuno- and cell-based assays were used to measure BCR binding to AChR and MuSK.
resultsThe frequency of polyreactive and autoreactive BCRs (n = 262) was higher in both AChR and MuSK MG patients than in healthy controls. None of the MG-derived BCRs bound AChR or MuSK.
interpretationThe results indicate that both these MG subtypes harbor defects in central and peripheral B cell tolerance checkpoints. Defective B cell tolerance may represent a fundamental contributor to autoimmunity in MG and is of particular importance when considering the durability of myasthenia gravis treatment strategies, particularly biologics that eliminate B cells.
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.