Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View
The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lym...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00138/full |
| _version_ | 1811343248932732928 |
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| author | Elizabeth A. Mills Yang Mao-Draayer Yang Mao-Draayer |
| author_facet | Elizabeth A. Mills Yang Mao-Draayer Yang Mao-Draayer |
| author_sort | Elizabeth A. Mills |
| collection | DOAJ |
| description | The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus. The manifestation of PML requires the presence of an active, genetically rearranged form of the JC virus within CNS glial cells, coupled with the loss of appropriate JC virus-specific immune responses. The reliability of metrics used to predict risk for PML could be improved if all three components, i.e., viral genetic strain, localization, and host immune function, were taken into account. Advances in our understanding of the critical lymphocyte subpopulation changes induced by these MS therapies and ability to detect viral mutation and reactivation will facilitate efforts to develop these metrics. |
| first_indexed | 2024-04-13T19:26:26Z |
| format | Article |
| id | doaj.art-19c8283cc8694486a29150865ea023de |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T19:26:26Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-19c8283cc8694486a29150865ea023de2022-12-22T02:33:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00138315701Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye ViewElizabeth A. Mills0Yang Mao-Draayer1Yang Mao-Draayer2Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, United StatesGraduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, United StatesThe increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus. The manifestation of PML requires the presence of an active, genetically rearranged form of the JC virus within CNS glial cells, coupled with the loss of appropriate JC virus-specific immune responses. The reliability of metrics used to predict risk for PML could be improved if all three components, i.e., viral genetic strain, localization, and host immune function, were taken into account. Advances in our understanding of the critical lymphocyte subpopulation changes induced by these MS therapies and ability to detect viral mutation and reactivation will facilitate efforts to develop these metrics.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00138/fullJohn Cunningham virusnatalizumabfingolimoddimethyl fumarateglia |
| spellingShingle | Elizabeth A. Mills Yang Mao-Draayer Yang Mao-Draayer Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View Frontiers in Immunology John Cunningham virus natalizumab fingolimod dimethyl fumarate glia |
| title | Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View |
| title_full | Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View |
| title_fullStr | Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View |
| title_full_unstemmed | Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View |
| title_short | Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View |
| title_sort | understanding progressive multifocal leukoencephalopathy risk in multiple sclerosis patients treated with immunomodulatory therapies a bird s eye view |
| topic | John Cunningham virus natalizumab fingolimod dimethyl fumarate glia |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00138/full |
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