title: Targeting plasma cells with proteasome inhibitors: possible roles in treating myasthenia gravis?
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.
authors.affiliation: School for Mental Health and Neuroscience, Maastricht University, the Netherlands.
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Gomez
authors.forename: Nick
authors.initials: N
authors.lastname: Willcox
authors.forename: Peter C
authors.initials: PC
authors.lastname: Molenaar
authors.forename: Wim
authors.initials: W
authors.lastname: Buurman
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez-Martinez
authors.forename: Marc H
authors.initials: MH
authors.lastname: De Baets
authors.forename: Mario
authors.initials: M
authors.lastname: Losen
mesh_terms: D001323:Autoantibodies / Q000378:metabolism; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D006801:Humans; D009157:Myasthenia Gravis / Q000188:drug therapy*; D010950:Plasma Cells / Q000187:drug effects* / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D011719:Pyrazines / Q000627:therapeutic use
chemical_list: D001323:Autoantibodies; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex