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B 细胞耗竭治疗原发性胆汁性肝硬化:利弊。

B cell depletion in treating primary biliary cirrhosis: pros and cons.

机构信息

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100032, China.

出版信息

World J Gastroenterol. 2012 Aug 14;18(30):3938-40. doi: 10.3748/wjg.v18.i30.3938.

Abstract

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.

摘要

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批准的唯一用于 PBC 患者的药物。尽管 PBC 的确切发病机制仍不清楚,但据推测,许多细胞群体,包括 B 细胞,参与了持续的炎症过程,这并不奇怪,B 细胞耗竭可能成为治疗这种疾病的潜在治疗靶点。利妥昔单抗是一种嵌合抗 CD20 单克隆抗体,已被批准用于治疗淋巴瘤和一些自身免疫性疾病,如类风湿关节炎。它是否对 PBC 的治疗有效尚未得到评估。最近,Tsuda 等人[1]表明,利妥昔单抗的 B 细胞耗竭可显著减少产生抗线粒体抗体(AMA)的 B 细胞数量、AMA 滴度、血浆免疫球蛋白(IgA、IgM 和 IgG)水平以及血清碱性磷酸酶,并且所有接受治疗的患者均耐受良好,无严重不良事件。这一观察结果为对 UDCA 反应不完全的 PBC 患者提供了一种新的治疗选择。

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