Related Experiment Video
Updated: Jan 4, 2026
Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis
Published on: November 17, 2020
Lack of specific T- and B-cell clonal expansions in multiple sclerosis patients with progressive multifocal
Diego Bertoli1,2, Alessandra Sottini1, Ruggero Capra3
1Centro di Ricerca Emato-oncologica AIL (CREA), Diagnostic Department, ASST Spedali Civili, Brescia, Italy.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is a rare, potentially devastating myelin-degrading disease caused by the JC virus. PML occurs preferentially in patients with compromised immune system, but has been also observed in multiple sclerosis (MS) patients treated with disease-modifying drugs. We characterized T and B cells in 5 MS patients that developed PML, 4 during natalizumab therapy and one after alemtuzumab treatment, and in treated patients who did not develop the disease. Results revealed that: i) thymic and bone marrow output was impaired in 4 out 5 patients at the time of PML development; ii) T-cell repertoire was restricted; iii) clonally expanded T cells were present in all patients. However, common usage or pairings of T-cell receptor beta variable or joining genes, specific clonotypes or obvious "public" T-cell response were not detected at the moment of PML onset. Similarly, common restrictions were not found in the immunoglobulin heavy chain repertoire. The data indicate that no JCV-related specific T- and B-cell expansions were mounted at the time of PML. The current results enhance our understanding of JC virus infection and PML, and should be taken into account when choosing targeted therapies.
Insights
Progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients is linked to immune changes, not specific JC virus-targeted T- and B-cell responses. This finding impacts treatment choices for MS patients at risk of PML.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease caused by the JC virus.
- PML predominantly affects immunocompromised individuals but is also seen in multiple sclerosis (MS) patients on disease-modifying therapies.
Purpose of the Study:
- To investigate the characteristics of T and B cells in MS patients who developed PML during or after specific treatments.
- To determine if specific T- and B-cell expansions related to JC virus infection are present at the onset of PML.
Main Methods:
- Analysis of T and B cell populations in 5 MS patients with PML (4 on natalizumab, 1 on alemtuzumab) and in treated MS patients without PML.
- Characterization of T-cell receptor and immunoglobulin heavy chain repertoires.
Main Results:
- Impaired thymic and bone marrow output observed in 4 out of 5 PML patients.
- Restricted T-cell repertoires and presence of clonally expanded T cells were noted in all PML patients.
- No common T-cell receptor or immunoglobulin gene usage, specific clonotypes, or public T-cell responses targeting JC virus were detected at PML onset.
Conclusions:
- The study suggests that PML development in MS patients is not associated with detectable JC virus-specific T- and B-cell expansions.
- Findings enhance understanding of JC virus pathogenesis and PML, informing therapeutic decisions for MS patients.
