Abstract
Progressive multifocal leukoencephalopathy (PML) has been described in association with a variety of predisposing risk factors, including HIV/AIDS, lymphoproliferative disorders and, most recently, treatment with a range of biologics, most notably natalizumab in multiple sclerosis (MS) (1). However, while these underlying disorders appear to be (usually) necessary, they are not sufficient to predict the development of PML, since only a small fraction of such individuals will succumb, raising the question of whether host genetic factors must also play a role. Evidence is mounting that this is, indeed, the case but more work needs to be done to fully delineate these underlying genetic factors. Finally, while it is possible that an underlying genetic susceptibility for PML in general will be uncovered in the future, the current evidence argues for a collection of multiple, individually rare underlying susceptibilities (with one predominant single genetic susceptibility in each individual), as described in this review.
Highlights
Progressive multifocal leukoencephalopathy (PML) is a severe, potentially fatal, CNS infection
While JC virus (JCV) is present at very high rates in the general population, PML remains a rare disorder, albeit an important one because of the clinical sequelae, and the recently demonstrated association with a variety of useful therapies, in particular natalizumab in multiple sclerosis (MS)
While the reports of rare individuals with PML in association with a confirmed primary immunodeficiency disorder (PID) immediately suggest a set of candidate genes that should be routinely searched for in PML patients, even when no such obvious diagnosis has been made, it is possible that a more subtle and specific immunodeficiency will explain the majority of cases of PML, namely an immunodeficiency that is not clinically recognizable except in the context of JCV
Summary
Progressive multifocal leukoencephalopathy (PML) has been described in association with a variety of predisposing risk factors, including HIV/AIDS, lymphoproliferative disorders and, most recently, treatment with a range of biologics, most notably natalizumab in multiple sclerosis (MS) [1]. While these underlying disorders appear to be (usually) necessary, they are not sufficient to predict the development of PML, since only a small fraction of such individuals will succumb, raising the question of whether host genetic factors must play a role. While it is possible that an underlying genetic susceptibility for PML in general will be uncovered in the future, the current evidence argues for a collection of multiple, individually rare underlying susceptibilities (with one predominant single genetic susceptibility in each individual), as described in this review
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
