ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neuroinfectious Diseases
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1584083
This article is part of the Research TopicProgressive Multifocal Leukoencephalopathy: From Risk Stratification to TreatmentView all 3 articles
JCV-specific Cell-Based Assays for PML Risk Assessment in Lupus and Multiple Sclerosis Patients with and without Natalizumab
Provisionally accepted
- 1University of Michigan, Ann Arbor, United States
- 2Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States
- 3Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States
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Background: Progressive 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.We 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.Methods: Our 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 IFN 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.We 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.
Keywords: PML, DMT, MS, Cytotoxicity index, OX40 immunity index, Natalizumab (Tysabri), SLE, BCDT
Received: 26 Feb 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Wu, Mills, Wang, Mao and Mao-Draayer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Mao-Draayer, Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, 73104, Oklahoma, United States
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