Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory Therapies
Top Cited Papers
Open Access
- 1 February 2010
- journal article
- review article
- Published by Annual Reviews in Annual Review of Medicine
- Vol. 61 (1) , 35-47
- https://doi.org/10.1146/annurev.med.080708.082655
Abstract
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the white matter of the human brain caused by lytic infection of oligodendrocytes with the human polyomavirus JCV. Although the majority of PML cases occur in severely immune-suppressed individuals, with HIV-1 infection as the predominant factor, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies that modulate immune system functions. Monoclonal antibodies that target the cell adhesion molecules VLA-4 (natalizumab; Tysabri for multiple sclerosis and Crohn's disease) or LFA-1 (efalizumab; Raptiva for severe forms of plaque psoriasis) to prevent extravasation of inflammatory T cells into tissues, or target the cell surface marker CD20 (rituximab; Rituxan for hematologic malignancies and rheumatoid arthritis) to deplete peripheral circulating B cells, have all been associated with PML. The link between the effects of these therapies on the immune system and the occurrence of PML has prompted investigations on JCV sites of latency in the bone marrow, the migration of bone marrow derived cells into the circulation, and intracellular virus entry into the brain.Keywords
This publication has 54 references indexed in Scilit:
- Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports projectBlood, 2009
- Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neuronsAnnals of Neurology, 2009
- Detection of JC Virus DNA and Proteins in the Bone Marrow of HIV‐Positive and HIV‐Negative Patients: Implications for Viral Latency and Neurotropic TransformationThe Journal of Infectious Diseases, 2009
- Adaptive Mutations in the JC Virus Protein Capsid Are Associated with Progressive Multifocal Leukoencephalopathy (PML)PLoS Genetics, 2009
- Detection of JC virus DNA fragments but not proteins in normal brain tissueAnnals of Neurology, 2008
- Multicenter Comparison of PCR Assays for Detection of Human Herpesvirus 6 DNA in SerumJournal of Clinical Microbiology, 2008
- Blockade of CD11a by Efalizumab in Psoriasis Patients Induces a Unique State of T-Cell HyporesponsivenessJournal of Investigative Dermatology, 2008
- Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumabBlood, 2008
- JC Virus Induces Nonapoptotic Cell Death of Human Central Nervous System Progenitor Cell-Derived AstrocytesJournal of Virology, 2004
- Involvement of JC Virus–Infected Mononuclear Cells from the Bone Marrow and Spleen in the Pathogenesis of Progressive Multifocal LeukoencephalopathyNew England Journal of Medicine, 1988