ArticleEBioMedicine2019
Interferon-β corrects massive gene dysregulation in multiple sclerosis: Short-term and long-term effects on immune regulation and neuroprotection.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Oligoprotein type I interferon signatures, but not TREX1 variants, increase risk of systemic lupus erythematosus in UK Biobank.Nature communications · 2026Pooled it
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Nucleoside-Analog Reverse-Transcriptase Inhibitors (NRTIs) Against Multiple Sclerosis: Comprehensive Review on a Possible Novel Therapeutic Approach.Neurology international · 2026Review
- Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2026Review
- Mitochondrial-Immune Dysfunction in MS: Therapeutic Potential of EV-Mediated Transfer.Cellular and molecular neurobiology · 2026Review
- Interpretable inflammation landscape of circulating immune cells.Nature medicine · 2026Article
- Interferons in Autoimmunity: From Loss of Tolerance to Chronic Inflammation.Biomedicines · 2025Review
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- Two roads diverged in multiple sclerosis: When is switching therapy effective?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Central TYK2 inhibition identifies TYK2 as a key neuroimmune modulator.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid.Communications biology · 2025Article
- Article
- Review
- Twenty Years of Subcutaneous Interferon-Beta-1a for Multiple Sclerosis: Contemporary Perspectives.Neurology and therapy · 2024Review
- Interferon Signature's Members, a Novel Altered Correlation upon Interferon-β Treatment in Multiple Sclerosis Patients.Current molecular medicine · 2024Article
- The effect of glatiramer acetate, IFNβ-1a, fingolimod, and dimethyl fumarate on the expression of T-bet, IFN-γ, and MEG3 in PBMC of RRMS patients.BMC research notes · 2023Article
- Shared Molecular Signatures Across Zika Virus Infection and Multiple Sclerosis Highlight AP-1 Transcription Factor as a Potential Player in Post-ZIKV MS-Like Phenotypes.Molecular neurobiology · 2023Article
- Clostridium epsilon toxin is excessive in multiple sclerosis and provokes multifocal lesions in mouse models.The Journal of clinical investigation · 2023Article
- T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Review
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundIn multiple sclerosis (MS), immune up-regulation is coupled to subnormal immune response to interferon-β (IFN-β) and low serum IFN-β levels. The relationship between the defect in IFN signalling and acute and long-term effects of IFN-β on gene expression in MS is inadequately understood.
methodsWe profiled IFN-β-induced transcriptome shifts, using high-resolution microarrays on 227 mononuclear cell samples from IFN-β-treated MS Complete Responders (CR) stable for five years, and stable and active Partial Responders (PR), stable and active untreated MS, and healthy controls.
findingsIFN-β injection induced short-term changes in 1,200 genes compared to baseline expression after 4-day IFN washout. Pre-injection after washout, and in response to IFN-β injections, PR more frequently had abnormal gene expression than CR. Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes (ILT, IDO1, PD-L1). Expression of 8,800 genes was dysregulated in therapy-naïve compared to IFN-β-treated patients. These long-term changes in protein-coding and long non-coding RNAs affect immunity, synaptic transmission, and CNS cell survival, and correct the disordered therapy-naïve transcriptome to near-normal. In keeping with its impact on clinical course and brain repair in MS, long-term IFN-β treatment reversed the overexpression of proinflammatory and MMP genes, while enhancing genes involved in the oligodendroglia-protective integrated stress response, neuroprotection, and immunoregulation. In the rectified long-term signature, 277 transcripts differed between stable PR and CR patients.
interpretationIFN-β had minimal short-term effects on Th1 and Th2 pathways, but long-term it corrected gene dysregulation and induced immunoregulatory and neuroprotective genes. These data offer new biomarkers for IFN-β responsiveness.
fundingUnrestricted grants from the US National MS Society, NMSS RG#4509A, and Bayer Pharmaceuticals.
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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.