Early relapses after the first dose of natalizumab in active multiple sclerosis patients
- Medicine, BiologyMultiple sclerosis
It is speculated that natalizumab can promote the release of inflammatory mediators from lymphocytes present in the central nervous system at the time of the first infusion, thus favoring the clinical manifestation of a pre-existing active lesion in patients with MS.
Update on PML: Lessons from the HIV uninfected and new insights in pathogenesis and treatment
- Medicine, BiologyCurrent HIV/AIDS reports
Recent advances in understanding of PML in HIV-uninfected patients in oncology, rheumatology, organ transplantation, and idiopathic immune deficiency and in association with novel therapeutics are summarized.
Overlapping and distinct mechanisms of action of multiple sclerosis therapies
- Medicine, PsychologyClinical Neurology and Neurosurgery
A bird's-eye view of T cells during natalizumab therapy
- Biology, MedicineNeurology
The main observations are that the TCR repertoire seems to “normalize” during natalizumab treatment, that is, revert to the state observed in healthy subjects, and the onset of PML and immune reconstitution inflammatory syndrome (IRIS) is accompanied or preceded by the appearance of distinct clonal T-cell expansions in blood or CSF.
JC Polyomavirus (JCV) and Monoclonal Antibodies: Friends or Potential Foes?
- Biology, MedicineClinical & developmental immunology
The need for PML risk stratification among natalizumab-treated patients and the need of effective therapeutic options are discussed under the light of the major viral models of PML etiopathogenesis.
Progressive multifocal leukoencephalopathy and other forms of JC virus disease
- Medicine, BiologyNature Reviews Neurology
The controversies surrounding JCV infection are critically appraised, the practical management guidelines for PML are provided, and reconstitution of the immune system affords the best prognosis for this condition.
Natalizumab treatment perturbs memory‐ and marginal zone‐like B‐cell homing in secondary lymphoid organs in multiple sclerosis
- Biology, MedicineEuropean journal of immunology
The ability of natalizumab to influence B‐cell migration and homeostasis through the splenic MZ, where JCV has been detected, adds to the list of nalozumab effects and may contribute to PML development by disseminating JCV.
Neuroprotection, regeneration and immunomodulation: broadening the therapeutic repertoire in multiple sclerosis
- Biology, PsychologyTrends in Neurosciences
Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis
- Biology, MedicineNeurology
Circulating B cells and especially pre-B cells are most prominently elevated among the studied immune cell subsets, raising the possibility that the effects and side effects of natalizumab are partly mediated by actions on B cells.
Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain
- Medicine, BiologyClinical Microbiology Reviews
The study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies.
SHOWING 1-10 OF 17 REFERENCES
Progressive multifocal leukoencephalopathy and natalizumab--unforeseen consequences.
- Medicine, PsychologyThe New England journal of medicine
Three patients in whom progressive multifocal leukoencephalopathy (PML) developed during treatment with natalizumab, a humanized monoclonal antibody against α4 integrins are described.
Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease.
- MedicineThe New England journal of medicine
Analysis of frozen serum samples showed that JC virus DNA had appeared in the serum three months after the initiation of open-label natalizumab monotherapy and two months before the appearance of symptomatic PML, suggesting that anti-alpha4-integrin therapy can result in JC virus-induced PML.
Natalizumab and PML
- Biology, MedicineNature Neuroscience
It is proposed that natalizumab treatment led to PML by mobilizing infected bone marrow cells, possibly in combination with reduced inflammatory and surveillance trafficking to the CNS, and if this hypothesis is correct, agents that do not affect bone marrow will lack this complication, whereas those affecting bone marrow and lymphoid organs require caution and surveillance.
Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab
- Medicine, PsychologyNature Reviews Drug Discovery
Three months after its expedited approval by the FDA, natalizumab was removed from the market after two cases of deadly progressive multifocal leukoencephalopathy were reported among the few thousand patients who had taken this drug in those clinical trials.
Immune surveillance in multiple sclerosis patients treated with natalizumab
- Medicine, BiologyAnnals of neurology
Whether natalizumab, an antibody against very late activating antigen (VLA)‐4, interferes with central nervous system immune surveillance as assessed by leukocyte cell numbers and cellular phenotypes in cerebrospinal fluid (CSF) and peripheral blood is tested.
Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis.
- Medicine, BiologyArchives of neurology
Natalizumab therapy decreased the CSF CD4(+)/CD8(+) ratio of patients with MS to levels similar to those of human immunodeficiency virus-infected patients, which may have implications for the observation that some natalizUMab-treated Patients with MS developed progressive multifocal leukoencephalopathy.
Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy.
- Biology, MedicineThe Journal of infectious diseases
Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions suggest mechanisms that may regulate cellular susceptibility to JCV infection and elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML.
Viral variant nucleotide sequences help expose leukocytic positioning in the JC virus pathway to the CNS
- Biology, MedicineJournal of leukocyte biology
In most literature, a dichotomy of the JCV regulatory region structure exists by tissue, but B lymphocytes have demonstrated the capacity to harbor JCV of diverse regulatory regions, which helps position their interaction with virus amid every stage of infection and implicates a lymphocytic role in latency.
The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms.
- BiologyTrends in immunology