ArticleJCI insight2018
Monocyte NOTCH2 expression predicts IFN-β immunogenicity in multiple sclerosis patients.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Current Knowledge about Nonclassical Monocytes in Patients with Multiple Sclerosis, a Systematic Review.International journal of molecular sciences · 2024Pooled it
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Systematic monocyte subset analysis reveals differential contribution of Notch signaling components to monocyte heterogeneity.iScience · 2025Article
- Innovative Medicines Initiative public-private partnerships to enhance translational safety.Nature reviews. Drug discovery · 2025Article
- Blood metabolomic and transcriptomic signatures stratify patient subgroups in multiple sclerosis according to disease severity.iScience · 2024Article
- Single-Cell Sequencing Combined with Transcriptome Sequencing Constructs a Predictive Model of Key Genes in Multiple Sclerosis and Explores Molecular Mechanisms Related to Cellular Communication.Journal of inflammation research · 2024Article
- Human Monocytes Plasticity in Neurodegeneration.Biomedicines · 2021Review
- Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases.Frontiers in immunology · 2021Review
- Post-Developmental Roles of Notch Signaling in the Nervous System.Biomolecules · 2020Review
- Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways.Frontiers in immunology · 2020Review
- Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ.Frontiers in immunology · 2020Article
- Expansion of Neutrophils and Classical and Nonclassical Monocytes as a Hallmark in Relapsing-Remitting Multiple Sclerosis.Frontiers in immunology · 2020Article
- Integrating the Ribonucleic Acid Sequencing Data From Various Studies for Exploring the Multiple Sclerosis-Related Long Noncoding Ribonucleic Acids and Their Functions.Frontiers in genetics · 2019Article
- Low Percentage of Signal Regulatory Protein α/βFrontiers in immunology · 2018Article
- Machine learning and single-cell RNA sequencing analyses identify MS-related monocytes and a five-gene candidate biomarker signature.Frontiers in neurologyArticle
Corrections and comments
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Authors and funding
23 authors at 13 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-β. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-β administration. Reduced monocyte NOTCH2 expression in nADA+ MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA+ patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-β administration.
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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.