JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab
BackgroundProgressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus and often fatal. Natalizumab is a highly effective therapy for multiple sclerosis (MS) but is linked to a high incidence of PML. The current metrics used to stratify MS patients at risk fo...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2025.1584083/full |
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| author | Qi Wu Qi Wu Elizabeth A. Mills Qin Wang Guangmei Mao Yang Mao-Draayer Yang Mao-Draayer |
| author_facet | Qi Wu Qi Wu Elizabeth A. Mills Qin Wang Guangmei Mao Yang Mao-Draayer Yang Mao-Draayer |
| author_sort | Qi Wu |
| collection | DOAJ |
| description | BackgroundProgressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus and often fatal. Natalizumab is a highly effective therapy for multiple sclerosis (MS) but is linked to a high incidence of PML. The current metrics used to stratify MS patients at risk for PML are incomplete, leading some patients to prematurely discontinue an effective treatment and others to develop PML despite perceived low risk.ObjectiveWe sought to develop a combination of cell-based assays using peripheral blood which can be used to provide a more comprehensive assessment of immune system function and complement existing PML risk metrics.MethodsOur assays measure general and JCV specific responses in CD4+ and CD8+ T cells following antigen stimulation. We examined responses in systemic lupus erythematosus (SLE) and MS patients with and without PML. Our cytotoxicity index (CTI) measures expression of IFNγ and the degranulation marker CD107a on CD8+ T cells, while our OX40 immunity index (OII) measures CD4+ T cell activation, as determined by OX40 and CD25 co-expression.Results and conclusionWe find that the combined metrics can be used to assess JCV immunocompetence, which can distinguish patients with and without PML, and could be used to predict and monitor PML patients from diagnosis onward to facilitate timely intervention. |
| format | Article |
| id | doaj-art-c105c679462e4052a2d4ef215d1bd475 |
| institution | DOAJ |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj-art-c105c679462e4052a2d4ef215d1bd4752025-08-20T02:56:09ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-08-011610.3389/fneur.2025.15840831584083JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumabQi Wu0Qi Wu1Elizabeth A. Mills2Qin Wang3Guangmei Mao4Yang Mao-Draayer5Yang Mao-Draayer6Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, United StatesAutoimmunity Center of Excellence, University of Michigan Medical School, Ann Arbor, MI, United StatesAlzheimer’s Drug Discovery Foundation, New York, NY, United StatesAutoimmunity Center of Excellence, University of Michigan Medical School, Ann Arbor, MI, United StatesSchool of Public Health, University of Michigan, Ann Arbor, MI, United StatesAutoimmunity Center of Excellence, University of Michigan Medical School, Ann Arbor, MI, United StatesAutoimmunity Center of Excellence, Multiple Sclerosis Center of Excellence, Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesBackgroundProgressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus and often fatal. Natalizumab is a highly effective therapy for multiple sclerosis (MS) but is linked to a high incidence of PML. The current metrics used to stratify MS patients at risk for PML are incomplete, leading some patients to prematurely discontinue an effective treatment and others to develop PML despite perceived low risk.ObjectiveWe sought to develop a combination of cell-based assays using peripheral blood which can be used to provide a more comprehensive assessment of immune system function and complement existing PML risk metrics.MethodsOur assays measure general and JCV specific responses in CD4+ and CD8+ T cells following antigen stimulation. We examined responses in systemic lupus erythematosus (SLE) and MS patients with and without PML. Our cytotoxicity index (CTI) measures expression of IFNγ and the degranulation marker CD107a on CD8+ T cells, while our OX40 immunity index (OII) measures CD4+ T cell activation, as determined by OX40 and CD25 co-expression.Results and conclusionWe find that the combined metrics can be used to assess JCV immunocompetence, which can distinguish patients with and without PML, and could be used to predict and monitor PML patients from diagnosis onward to facilitate timely intervention.https://www.frontiersin.org/articles/10.3389/fneur.2025.1584083/fullPMLDMTMScytotoxicity indexOX40 immunity indexnatalizumab (Tysabri) |
| spellingShingle | Qi Wu Qi Wu Elizabeth A. Mills Qin Wang Guangmei Mao Yang Mao-Draayer Yang Mao-Draayer JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab Frontiers in Neurology PML DMT MS cytotoxicity index OX40 immunity index natalizumab (Tysabri) |
| title | JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab |
| title_full | JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab |
| title_fullStr | JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab |
| title_full_unstemmed | JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab |
| title_short | JCV-specific cell-based assays for PML risk assessment in lupus and multiple sclerosis patients with and without natalizumab |
| title_sort | jcv specific cell based assays for pml risk assessment in lupus and multiple sclerosis patients with and without natalizumab |
| topic | PML DMT MS cytotoxicity index OX40 immunity index natalizumab (Tysabri) |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1584083/full |
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