School for Mental Health and Neuroscience, Maastricht University, the Netherlands.
Ann N Y Acad Sci. 2012 Dec;1274:48-59. doi: 10.1111/j.1749-6632.2012.06824.x.
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.
重症肌无力（MG）主要采用广谱免疫抑制剂治疗，如泼尼松或硫唑嘌呤，这些药物通常需要数月才能显著降低自身抗体滴度。这种延迟可能是由于主要产生抗体的细胞——浆细胞对这些药物的耐药性所致。特别是，长寿浆细胞对免疫抑制治疗有耐药性，并能在数月内产生（自身）抗体。硼替佐米是一种蛋白酶体抑制剂，已被批准用于治疗多发性骨髓瘤，即浆细胞恶性肿瘤。最近在细胞培养和动物模型中的临床前研究，以及在器官移植受者中的临床研究，表明硼替佐米可以在数小时内杀死非肿瘤浆细胞。这表明蛋白酶体抑制剂也可用于快速减少自身免疫性疾病中的自身抗体产生。我们已开始评估它们在 MG 中的潜力。
