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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. 2018 11; 25(11):1384-1388.EJ

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.

Authors+Show Affiliations

MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.Department of Neuroinflammation, National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK. Neuroimmunology and CSF Laboratory, Institute of Neurology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.Neuroimmunology and CSF Laboratory, Institute of Neurology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30035842

Citation

Keddie, S, et al. "Plasma Cell Depletion With Bortezomib in the Treatment of Refractory N-methyl-d-aspartate (NMDA) Receptor Antibody Encephalitis. Rational Developments in Neuroimmunological Treatment." European Journal of Neurology, vol. 25, no. 11, 2018, pp. 1384-1388.
Keddie S, Crisp SJ, Blackaby J, et al. 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. 2018;25(11):1384-1388.
Keddie, S., Crisp, S. J., Blackaby, J., Cox, A., Coles, A., Hart, M., Church, A. J., Vincent, A., Zandi, M., & Lunn, M. P. (2018). Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment. European Journal of Neurology, 25(11), 1384-1388. https://doi.org/10.1111/ene.13759
Keddie S, et al. 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. 2018;25(11):1384-1388. PubMed PMID: 30035842.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment. AU - Keddie,S, AU - Crisp,S J, AU - Blackaby,J, AU - Cox,A, AU - Coles,A, AU - Hart,M, AU - Church,A J, AU - Vincent,A, AU - Zandi,M, AU - Lunn,M P, Y1 - 2018/08/31/ PY - 2018/04/05/received PY - 2018/07/19/accepted PY - 2018/7/24/pubmed PY - 2019/4/17/medline PY - 2018/7/24/entrez KW - NMDA KW - bortezomib KW - encephalitis KW - neuroimmunology KW - plasma cell SP - 1384 EP - 1388 JF - European journal of neurology JO - Eur. J. Neurol. VL - 25 IS - 11 N2 - 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. SN - 1468-1331 UR - https://www.unboundmedicine.com/medline/citation/30035842/Plasma_cell_depletion_with_bortezomib_in_the_treatment_of_refractory_N_methyl_d_aspartate__NMDA__receptor_antibody_encephalitis__Rational_developments_in_neuroimmunological_treatment_ L2 - https://doi.org/10.1111/ene.13759 DB - PRIME DP - Unbound Medicine ER -