ArticleJournal of neuroinflammation2012
Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 61 citations in OpenAlex.
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- Interferon Regulatory Factors as a Potential Therapeutic Target for Neuroinflammation: A Focus on Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Comparative transcriptome profiling of the lumbosacral dorsal root ganglia reveals sexually dimorphic gene expression in a murine model of coronavirus-induced neurodegeneration.American journal of clinical and experimental urology · 2025Article
- Defective Induction of IL-27-Mediated Immunoregulation by Myeloid DCs in Multiple Sclerosis.International journal of molecular sciences · 2023Article
- Immune cells transcriptome-based drug repositioning for multiple sclerosis.Frontiers in immunology · 2022Article
- Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus.PloS one · 2022Article
- ETV7 limits antiviral gene expression and control of influenza viruses.Science signaling · 2021Article
- Bayesian approach for predicting responses to therapy from high-dimensional time-course gene expression profiles.BMC bioinformatics · 2021Article
- Identification and Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Relapsing-Remitting Multiple Sclerosis.Frontiers in immunology · 2021Article
- Article
- Elastic net-based prediction of IFN-β treatment response of patients with multiple sclerosis using time series microarray gene expression profiles.Scientific reports · 2019Article
- Pattern Recognition Receptors in Multiple Sclerosis and Its Animal Models.Frontiers in immunology · 2019Review
- Close Encounters of the First Kind: Innate Sensors and Multiple Sclerosis.Molecular neurobiology · 2017Review
- Disease-modifying therapies and infectious risks in multiple sclerosis.Nature reviews. Neurology · 2016Review
- Absence of MxA induction is related to a poor clinical response to interferon beta treatment in multiple sclerosis patients.Journal of neurology · 2016Observational
- Review
- Identifying Multi-Dimensional Co-Clusters in Tensors Based on Hyperplane Detection in Singular Vector Spaces.PloS one · 2016Article
- [Immunotherapy and infectious issues in multiple sclerosis. Self-injectable and oral drugs for immunotherapy].Der Nervenarzt · 2015Article
- Solving the puzzle of autoimmunity: critical questions.F1000prime reports · 2015Review
- Enhanced in vivo efficacy of a type I interferon superagonist with extended plasma half-life in a mouse model of multiple sclerosis.The Journal of biological chemistry · 2014Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA subset of patients with multiple sclerosis (MS) shows an increased endogenous IFN-like activity before initiation of IFN-beta treatment. The molecular basis of this phenomenon and its relevance to predict individual therapy outcomes are not yet fully understood. We studied the expression patterns of these patients, the prognostic value of an elevated IFN-like activity, and the gene regulatory effects of exogenously administered IFN-beta.
methodsMicroarray gene expression profiling was performed for 61 MS patients using peripheral blood mononuclear cells obtained before and after 1 month of IFN-beta therapy. Expression levels of genes involved in pathways either inducing or being activated by IFN-beta were compared between patients with high (MX1(high) cohort) and low (MX1(low) cohort) endogenous IFN-like activity. Patients were followed for 5 years and relapses as well as progression on the expanded disability status scale (EDSS) were documented.
resultsBefore the start of therapy, 11 patients presented elevated mRNA levels of IFN-stimulated genes indicative of a relatively high endogenous IFN-like activity (MX1(high)). In these patients, pathogen receptors (for example, TLR7, RIG-I and IFIH1) and transcription factors were also expressed more strongly, which could be attributed to an overactivity of IFN-stimulated gene factor 3 (ISGF3, a complex formed by STAT1, STAT2 and IFN regulatory factor 9). After 1 month of IFN-beta therapy, the expression of many pathway genes was significantly induced in MX1(low) patients, but remained unaltered in MX1(high) patients. During follow-up, relapse rate and changes in EDSS were comparable between both patient groups, with differences seen between different types of IFN-beta drug application.
conclusionsTherapeutic IFN-beta induces the transcription of several genes involved in IFN-related pathways. In a subgroup of MS patients, the expression of these genes is already increased before therapy initiation, possibly driven by an overexpression of ISGF3. Patients with high and low endogenous IFN-like activity showed similar clinical long-term courses of disease. Different results were obtained for different IFN-beta drug preparations, and this merits further investigation.
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