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Published on: November 23, 2013
Monoclonal antibodies and progressive multifocal leukoencephalopathy
Joseph R Berger1, Sidney A Houff, Eugene O Major
1Department of Neurology, University of Kentucky College of Medicine, Lexington, Kentucky, USA. jrbneuro@uky.edu
Mabs
|January 16, 2010
Summary
Monoclonal antibodies can increase the risk of progressive multifocal leukoencephalopathy (PML), a rare brain disease. This study explains the link between certain monoclonal antibodies, like natalizumab, and PML development.
Area of Science:
- Neuroimmunology
- Virology
- Oncology
Background:
- Monoclonal antibodies (mAbs) are widely used therapeutics, but immune perturbation can lead to opportunistic infections and malignancies.
- Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease caused by JC virus reactivation in immunosuppressed individuals.
- PML has been identified as a potential complication of certain mAb therapies, particularly in patients with multiple sclerosis and Crohn disease.
Purpose of the Study:
- To investigate the association between specific monoclonal antibodies and the development of progressive multifocal leukoencephalopathy (PML).
- To propose a biological explanation for the increased risk of PML observed with natalizumab and other select monoclonal antibodies.
Main Methods:
- Review of clinical data and biological mechanisms linking monoclonal antibody use to PML.
- Analysis of the pathogenesis of JC virus infection and its relationship to immune suppression induced by mAbs.
- Examination of specific mAbs, including natalizumab, efalizumab, and rituximab, in relation to PML incidence.
Main Results:
- Natalizumab, an integrin inhibitor, and efalizumab, used for psoriasis, have been associated with PML.
- An increased risk of PML is suggested for rituximab, though often in patients with predisposing B-cell disorders.
- The study explores the biological rationale behind the observed PML risk with these therapeutic agents.
Conclusions:
- Certain monoclonal antibodies, notably natalizumab, are associated with an increased risk of PML.
- Understanding the interplay between JC virus, immune function, and mAb therapy is crucial for risk assessment.
- Further research into the pathogenesis of PML in the context of immunosuppression is warranted.
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