ArticleBrain pathology (Zurich, Switzerland)2021
CNS inflammation after natalizumab therapy for multiple sclerosis: A retrospective histopathological and CSF cohort study.
Article in Brain pathology (Zurich, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.Pharmacological reviews · 2026Review
- Brain Immune Cell Composition in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy After Natalizumab: An Immunohistochemical Cohort Study.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- No association between the wearing-off effect and α4-integrin receptor saturation in natalizumab treated patients with relapsing-remitting multiple sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Observational
- Annual 12-Week Dosing Gap of Natalizumab: Clinical Efficacy, Blood Biomarkers, and CSF Cell Composition.Annals of clinical and translational neurology · 2026Observational
- FABP7 is increased in progressive multiple sclerosis and induces a pro-inflammatory phenotype in monocytes through a glycolytic switch.Nature communications · 2025Article
- Endothelial -targeted CD39 is protective in a mouse model of global forebrain ischaemia.Journal of neuroinflammation · 2025Article
- Plasma cells in and around the central nervous system.Frontiers in immunology · 2025Review
- CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis.International journal of molecular sciences · 2024Review
- Specific myeloid signatures in peripheral blood differentiate active and rare clinical phenotypes of multiple sclerosis.Frontiers in immunology · 2023Article
- Intruders or protectors - the multifaceted role of B cells in CNS disorders.Frontiers in cellular neuroscience · 2023Review
- Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.Journal of neuroinflammation · 2022Review
- Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis.The Journal of experimental medicine · 2022Article
- B cells in central nervous system disease: diversity, locations and pathophysiology.Nature reviews. Immunology · 2022Review
- Breaching Brain Barriers: B Cell Migration in Multiple Sclerosis.Biomolecules · 2022Review
- Immunopathology of Tumefactive Demyelinating Lesions-From Idiopathic to Drug-Related Cases.Frontiers in neurology · 2022Review
- Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natalizumab, a recombinant humanized monoclonal antibody directed against the α4 subunit of the integrins α4ß1 and α4ß7, has been approved for the treatment of active relapsing-remitting MS. Although natalizumab is a highly beneficial drug that effectively reduces the risk of sustained disability progression and the rate of clinical relapses, some patients do not respond to it, and some are at higher risk of developing progressive multifocal leukoencephalopathy (PML). The histopathological effects after natalizumab therapy are still unknown. We, therefore, performed a detailed histological characterization of the CNS inflammatory cell infiltrate of 24 brain specimens from natalizumab treated patients, consisting of 20 biopsies and 4 autopsies and 21 MS controls. To complement the analysis, immune cells in blood and cerebrospinal fluid (CSF) of 30 natalizumab-treated patients and 42 MS controls were quantified by flow cytometry. Inflammatory infiltrates within lesions were mainly composed of T cells and macrophages, some B cells, plasma cells, and dendritic cells. There was no significant difference in the numbers of T cells or macrophages and microglial cells in lesions of natalizumab-treated patients as compared to controls. A shift towards cytotoxic T cells of a memory phenotype was observed in the CSF. Plasma cells were significantly increased in active demyelinating lesions of natalizumab-treated patients, but no correlation to clinical disability was observed. Dendritic cells within lesions were found to be reduced with longer ongoing therapy duration. Our findings suggest that natalizumab does not completely prevent immune cells from entering the CNS and is associated with an accumulation of plasma cells, the pathogenic and clinical significance of which is not known. As B cells are considered to serve as a reservoir of the JC virus, the observed plasma cell accumulation and reduction in dendritic cells in the CNS of natalizumab-treated patients may potentially play a role in PML development.
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Registered trials
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