Highlights
- •Post-mortem brain from an unusual, fulminant case of MS after natalizumab withdrawal is analyzed.
- •Widespread EBV latent and lytic infection is found in multiple white matter lesions.
- •EBV lytically infected cells and granzyme B+CD8+T cells are more frequent in active lesions.
- •Uncontrolled EBV reactivation in the CNS during natalizumab therapy causes hyperinflammation after drug discontinuation.
Abstract
Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal
is a potentially life-threatening event. To verify whether highly destructive inflammation
after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation
in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we
analyzed post-mortem brain tissue from a patient who died during a fulminating MS
relapse following natalizumab withdrawal. Numerous EBV infected B cells/plasma cells
and CD8+ T cells infiltrated all white matter lesions; the highest frequency of EBV lytically
infected cells and granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These results may encourage
switching to B-cell depleting therapy after natalizumab discontinuation.
Graphical abstract

Graphical Abstract
Keywords
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Article Info
Publication History
Published online: March 18, 2017
Accepted:
March 15,
2017
Received in revised form:
March 8,
2017
Received:
February 8,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
