Monoclonal antibodies and progressive multifocal leukoencephalopathy
- 1 November 2009
- journal article
- Published by Informa UK Limited in mAbs
- Vol. 1 (6), 583-589
- https://doi.org/10.4161/mabs.1.6.9884
Abstract
Since their introduction, monoclonal antibodies have found an ever expanding role in the treatment of a wide number of disorders. However, the perturbation of the immune system that attends their use may also increase the risk for the development of disorders that arise in the setting of immunosuppressive conditions, such as, opportunistic infection and malignancy. In this paper, we address the association between some monoclonal antibodies and the development of a rare demyelinating disease of the brain, progressive multifocal leukoencephalopathy (PML). PML results from infection with a ubiquitous polyoma virus, JC virus, and typically occurs in the setting of impaired immunity, most commonly, AIDS. It was first recognized as a potential complication of monoclonal antibody therapy in patients with multiple sclerosis and Crohn disease being treated with natalizumab, an α4β1 and α4β7 integrin inhibitor. Subsequently, efalizumab, a monoclonal antibody used in the treatment of psoriasis, was also demonstrated to be associated with PML. An increased risk has been suggested for rituximab, although most of the patients developing PML with that monoclonal antibody have been treated for B cell disorders that predispose to the development of PML. Based on our current understanding of the biology of JC virus and the pathogenesis of PML, we propose an explanation for the increased risk for PML that is observed with natalizumab and certain other monoclonal antibodies.Keywords
This publication has 82 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
- Adaptive Mutations in the JC Virus Protein Capsid Are Associated with Progressive Multifocal Leukoencephalopathy (PML)PLoS Genetics, 2009
- Efficient in vitro expansion of JC virus-specific CD8+ T-cell responses by JCV peptide-stimulated dendritic cells from patients with progressive multifocal leukoencephalopathyVirology, 2009
- Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: Are patients with systemic lupus erythematosus at particular risk?Autoimmunity Reviews, 2008
- Reactivation of Human Herpesvirus-6 in Natalizumab Treated Multiple Sclerosis PatientsPLOS ONE, 2008
- Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathyJournal of NeuroVirology, 2008
- Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patientsJournal of Neuroimmunology, 2006
- Alemtuzumab in CLL and Other Lymphoid NeoplasmsCancer Investigation, 2006
- 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
- Progressive Multifocal Leukoencephalopathy in a Male Homosexual with T-Cell Immune DeficiencyNew England Journal of Medicine, 1982