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Targeting plasma cells with proteasome inhibitors: possible roles in treating myasthenia gravis?
Author(s) -
Gomez Alejandro M.,
Willcox Nick,
Molenaar Peter C.,
Buurman Wim,
MartinezMartinez Pilar,
De Baets Marc H.,
Losen Mario
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06824.x
Subject(s) - myasthenia gravis , bortezomib , azathioprine , proteasome inhibitor , plasma cell , prednisone , multiple myeloma , proteasome , immunology , autoantibody , medicine , antibody , plasma cell myeloma , malignancy , pharmacology , chemistry , disease , biochemistry
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.