Targeting plasma cells with proteasome inhibitors: possible roles in treating myasthenia gravis?

Alejandro M. Gomez, Nick Willcox, Peter C. Molenaar, Wim A. Buurman, Pilar Martinez-Martinez, Marc H. De Baets, Mario Losen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Web of Science)

Abstract

Myasthenia gravis (MG) is treated primarily with broad-spectrum immuno-suppressants such as prednisone or azathioprine, which normally require several months to reduce autoantibody titers significantly. This delay may be caused by the resistance of the main antibody-producing cells, the plasma cells, to these drugs. In particular, long-lived plasma cells are resistant to immunosuppressive treatments and can produce (auto-) antibodies for months. Bortezomib is a proteasome inhibitor approved for treating patients with multiple myeloma, a plasma cell malignancy. Recent preclinical studies in cell cultures and animal models, and clinical studies in organ-transplant recipients, have demonstrated that bortezomib can kill non-neoplastic plasma cells within hours. This suggests that proteasome inhibitors could also be used for rapidly reducing autoantibody production in autoimmune diseases. We have begun to assess their potential in MG.
Original languageEnglish
Pages (from-to)48-59
JournalAnnals of the New York Academy of Sciences
Volume1274
DOIs
Publication statusPublished - 2012

Keywords

  • bortezomib
  • plasma cell
  • myasthenia gravis
  • proteasome inhibition
  • autoimmunity

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