Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment.
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Authors
Keddie, S
Blackaby, J
Cox, A
Hart, M
Church, AJ
Vincent, A
Zandi, M
Lunn, MP
Publication Date
2018-11Journal Title
Eur J Neurol
ISSN
1351-5101
Publisher
Wiley
Volume
25
Issue
11
Pages
1384-1388
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Keddie, S., Crisp, S., Blackaby, J., Cox, A., Coles, A., Hart, M., Church, A., et al. (2018). Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment.. Eur J Neurol, 25 (11), 1384-1388. https://doi.org/10.1111/ene.13759
Abstract
BACKGROUND AND PURPOSE: The aim was to assess the therapeutic potential of bortezomib in the treatment of refractory N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis and its potential in other immune-mediated, B-cell-driven neurological diseases. METHODS: Two cases of severe NMDAR antibody encephalitis, resistant to first and second line therapy with steroids, intravenous immunoglobulins, plasma exchange, cyclophosphamide and rituximab, were treated with four and five cycles of 1.3 mg/m2 bortezomib at 350 and 330 days following initial presentation. RESULTS: Both patients showed significant clinical improvement with reductions of NMDAR antibody titres following bortezomib treatment. This is the first case in the literature where the NMDAR antibody level was undetectable following treatment with bortezomib. CONCLUSION: Bortezomib's unique ability to target long-lived autoreactive plasma cells appears to be a useful adjunct to standard second line immunosuppressive therapy in treatment-refractory NMDAR antibody encephalitis. The drug's pharmacodynamics, cell targeting and mechanism of action are reviewed, and it is postulated that bortezomib may be useful in a host of B-cell-driven neuroimmunological diseases.
Keywords
Plasma Cells, Humans, Receptors, N-Methyl-D-Aspartate, Antineoplastic Agents, Treatment Outcome, Adult, Female, Anti-N-Methyl-D-Aspartate Receptor Encephalitis, Bortezomib
Sponsorship
nil
Identifiers
External DOI: https://doi.org/10.1111/ene.13759
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280584
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