ArticleNeurology2012
Fatal PML associated with efalizumab therapy: insights into integrin αLβ2 in JC virus control.
Article in Neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 109 citations in OpenAlex.
- Therapeutic Applications of Immunobiologics in Autoimmune and Inflammatory Diseases.Pharmaceutics · 2026Review
- Increased Anti-Psoriatic Effect of Anti-Inflammatory Dendrimers Using Fluid Catanionic Vesicle-Based Topical Formulations.Advanced healthcare materials · 2026Article
- JC Polyomavirus Infection: A Narrative Review.Infectious diseases and therapy · 2025Review
- Humanized anti-CD11d monoclonal antibodies suitable for basic research and therapeutic applications.Antibody therapeutics · 2025Article
- JC virus spread is potentiated by glial replication and demyelination-linked glial proliferation.Brain : a journal of neurology · 2024Article
- Review
- High levels of endothelial ICAM-1 prohibit natalizumab mediated abrogation of CD4Journal of neuroinflammation · 2023Article
- Understanding polyomavirus CNS disease - a perspective from mouse models.The FEBS journal · 2022Review
- Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline.Journal of psoriasis and psoriatic arthritis · 2021Article
- Endogenous memory T cells with donor-reactivity: early post-transplant mediators of acute graft injury in unsensitized recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2021Review
- Type O blood group associates with higher anti-JC polyomavirus antibody levels.Brain and behavior · 2021Article
- Identifying RNA Biomarkers and Molecular Pathways Involved in Multiple Subtypes of Uveitis.American journal of ophthalmology · 2021Article
- A Case of John Cunningham Virus Induced Rhombencephalitis after Rituximab Therapy for Idiopathic Thrombocytopenic Purpura.Case reports in infectious diseases · 2021Article
- β2 Integrin CD11d/CD18: From Expression to an Emerging Role in Staged Leukocyte Migration.Frontiers in immunology · 2021Review
- Role of LFA-1 integrin in the control of a lymphocytic choriomeningitis virus (LCMV) infection.Virulence · 2020Article
- JCPyV VP1 Mutations in Progressive MultifocalLeukoencephalopathy: Altering Tropismor Mediating Immune Evasion?Viruses · 2020Review
- Article
- Review
- β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease.International journal of molecular sciences · 2020Review
- Human CD4Fluids and barriers of the CNS · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesProgressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders.
methodsWe report 2 patients with severe psoriasis and fatal PML treated for ≥3 years with efalizumab, a neutralizing antibody to αLβ2-leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients.
resultsBoth patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE.
conclusionsFrom these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector-phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control.
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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.