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 Nov;25(11):1384-1388. doi: 10.1111/ene.13759. Epub 2018 Aug 31.

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: NMDA; bortezomib; encephalitis; neuroimmunology; plasma cell.

Publication types

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

MeSH terms

  • Adult
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / drug therapy*
  • Antineoplastic Agents / therapeutic use*
  • Bortezomib / therapeutic use*
  • Female
  • Humans
  • Plasma Cells
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Receptors, N-Methyl-D-Aspartate
  • Bortezomib