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B cell depletion in treating primary biliary cirrhosis: Pros and cons

机译:B细胞耗竭治疗原发性胆汁性肝硬化的利弊

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摘要

Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease of unknown etiology that affects almost exclusively women. Ursodeoxycholic acid (UDCA) is currently the only approved drug by Food and Drug Administration for patients with PBC. Although the precise pathogenesis of PBC remains unclear, it has been postulated that many cell populations, including B cells, are involved in the ongoing inflammatory process, which implicates, not surprisingly, a potential therapeutic target of depleting B cell to treat this disorder. Rituximab is a chimeric anti-CD20 monoclonal antibody that has been approved for the treatment of lymphoma and some autoimmune diseases such as rheumatoid arthritis. Whether it is effective in the treatment of PBC has not been evaluated. Recently, Tsuda et al[1] demonstrated that B cell depletion with rituximab significantly reduced the number of anti-mitochondrial antibodies (AMA)-producing B cells, AMA titers, the plasma levels of immunoglobulins (IgA, IgM and IgG) as well as serum alkaline phosphatase, and it was well tolerated by all the treated patients with no serious adverse events. This observation provides a novel treatment option for the patients with PBC who have incomplete response to UDCA.
机译:原发性胆汁性肝硬化(PBC)是一种病因不明的进行性自身免疫性肝病,几乎仅影响女性。熊去氧胆酸(UDCA)是目前美国食品和药物管理局唯一批准用于PBC患者的药物。尽管尚不清楚PBC的确切发病机理,但据推测,包括B细胞在内的许多细胞群都参与了正在进行的炎症过程,这毫无疑问地暗示了消耗B细胞治疗这种疾病的潜在治疗靶点。利妥昔单抗是一种嵌合的抗CD20单克隆抗体,已被批准用于治疗淋巴瘤和某些自身免疫性疾病,例如类风湿关节炎。尚未评估其在治疗PBC中是否有效。最近,Tsuda等人[sup> [1] 表明,用利妥昔单抗清除B细胞可显着减少产生抗线粒体抗体(AMA)的B细胞数量,AMA滴度,免疫球蛋白(IgA, IgM和IgG)以及血清碱性磷酸酶,所有接受治疗的患者都对它具有良好的耐受性,没有严重的不良事件。该观察结果为对UDCA反应不完全的PBC患者提供了一种新颖的治疗选择。

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