ArticlePloS one2014
A complex role of herpes viruses in the disease process of multiple sclerosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Up-to-date knowledge about the association between multiple sclerosis and the reactivation of human endogenous retrovirus infections.Journal of neurology · 2018Pooled it
- Experimental Therapies in Multiple Sclerosis: Epstein-Barr Virus and Potential EBV-Related Therapeutic Strategies-A Systematic Review.Journal of clinical medicine · 2026Review
- Epstein-barr virus and multiple sclerosis: from pathogenesis and diagnosis to EBV-specific T cell therapy and gene-targeted therapeutics.Journal of applied genetics · 2026Review
- Intrathecally expanded GZMK+/GZMH+ CD8 T cells targeting EBV antigens may reduce severity of Multiple Sclerosis.medRxiv : the preprint server for health sciences · 2025Article
- Expanded T lymphocytes in the cerebrospinal fluid of multiple sclerosis patients are specific for Epstein-Barr-virus-infected B cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stabilization of leukocytes from cerebrospinal fluid for central immunophenotypic evaluation in multicenter clinical trials.Journal of immunological methods · 2022Article
- The Age-Related Efficacy of Dimethyl Fumarate and Natalizumab in the Real-World Management of Multiple Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis.Frontiers in immunology · 2021Review
- Asymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2021Article
- Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation.Clinical microbiology reviews · 2020Review
- A logistic regression analysis of risk factors in ME/CFS pathogenesis.BMC neurology · 2019Article
- Reappraisal of Human HOG and MO3.13 Cell Lines as a Model to Study Oligodendrocyte Functioning.Cells · 2019Article
- Intrathecal, Not Systemic Inflammation Is Correlated With Multiple Sclerosis Severity, Especially in Progressive Multiple Sclerosis.Frontiers in neurology · 2019Article
- Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology.Neural regeneration research · 2018Review
- Intrathecal B Cells in MS Have Significantly Greater Lymphangiogenic Potential Compared to B Cells Derived From Non-MS Subjects.Frontiers in neurology · 2018Article
- Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients.Acta neuropathologica · 2017Article
- Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.Frontiers in neurology · 2017Article
- Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis.Annals of clinical and translational neurology · 2016Article
- Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination.Neurology(R) neuroimmunology & neuroinflammation · 2016Article
- Pioglitazone regulates myelin phagocytosis and multiple sclerosis monocytes.Annals of clinical and translational neurology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). Neither the antigenic target(s) nor the cell population(s) responsible for CNS tissue destruction in MS have been fully defined. The objective of this study was to simultaneously determine the antigen (Ag)-specificity and phenotype of un-manipulated intrathecal CD4+ and CD8+ T cells of patients with relapsing-remitting and progressive MS compared to subjects with other inflammatory neurological diseases. We applied a novel Ag-recognition assay based on co-cultures of freshly obtained cerebrospinal fluid T cells and autologous dendritic cells pre-loaded with complex candidate Ag's. We observed comparably low T cell responses to complex auto-Ag's including human myelin, brain homogenate, and cell lysates of apoptotically modified oligodendroglial and neuronal cells in all cohorts and both compartments. Conversely, we detected a strong intrathecal enrichment of Epstein-Barr virus- and human herpes virus 6-specific (but not cytomegalovirus-specific) reactivities of the Th1-phenotype throughout all patients. Qualitatively, the intrathecal enrichment of herpes virus reactivities was more pronounced in MS patients. This enrichment was completely reversed by long-term treatment with the IL-2 modulating antibody daclizumab, which strongly inhibits MS disease activity. Finally, we observed a striking discrepancy between diminished intrathecal T cell proliferation and enhanced cytokine production of herpes virus-specific T cells among progressive MS patients, consistent with the phenotype of terminally differentiated cells. The data suggest that intrathecal administration of novel therapeutic agents targeting immune cells outside of the proliferation cycle may be necessary to effectively eliminate intrathecal inflammation in progressive MS.
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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.