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Updated: May 26, 2026
06:02
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
The link between VLA-4 and JC virus reactivation
Maria Chiara G Monaco1, Eugene O Major
1Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Expert Review of Clinical Immunology
|December 14, 2011
Summary
Natalizumab is an effective therapy for multiple sclerosis and Crohn's disease but carries a risk of progressive multifocal leukoencephalopathy (PML) due to JC virus reactivation. This risk increases with treatment duration and patient history.
Area of Science:
- Neuroimmunology
- Gastroenterology
- Virology
Background:
- Natalizumab is a biologic therapy used for relapsing-remitting multiple sclerosis and Crohn's disease.
- It functions by inhibiting inflammatory cell migration to the central nervous system and gut.
- A significant risk associated with natalizumab is progressive multifocal leukoencephalopathy (PML), a condition caused by JC virus reactivation.
Purpose of the Study:
- To highlight the increased incidence of PML in natalizumab-treated patients.
- To discuss the implications of PML as a complication in patients receiving immunomodulatory treatments.
- To explore the pathogenesis of PML and JC virus latency in the context of natalizumab therapy.
Main Methods:
- Review of existing literature and clinical data on natalizumab treatment and PML incidence.
- Analysis of risk factors contributing to PML development, including JC virus seropositivity and prior immunosuppressive therapy.
- Investigation into the biological mechanisms underlying JC virus latency and brain trafficking.
Main Results:
- The incidence of PML in natalizumab-treated patients is approximately 1.5:750.
- This risk escalates to approximately 1:100 for patients receiving 24-36 doses, particularly those with a history of immunosuppression and JC virus antibodies.
- PML has transitioned from a rare condition to a notable complication in patients undergoing immunomodulatory treatments.
Conclusions:
- Natalizumab therapy, while effective, necessitates careful monitoring due to the associated risk of PML.
- Understanding JC virus latency and trafficking is crucial for mitigating PML risk.
- The study underscores the importance of risk-benefit assessment in long-term immunomodulatory treatments.
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