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B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as therapeutic targets

机译:中枢神经系统自身免疫中基于B细胞的疗法:区分CD19和CD20作为治疗靶标

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摘要

Increasing recognition of the role of B cells in the adaptive immune response makes B cells an important therapeutic target in autoimmunity. Numerous current and developmental immunotherapies target B cells for elimination through recognition of cell-surface proteins expressed specifically on B cells, in particular CD19 and CD20. Similarities and differences in the function and expression of these two molecules predict some shared, and some distinct, pharmacological effects of agents targeting CD19 versus CD20, potentially leading to differences in the clinical safety and efficacy of such agents. Here, we review current knowledge of CD19 and CD20 function and biology, survey current and developmental therapies that target these molecules, and discuss potential differences in elimination of B cells by drugs that target CD19 versus CD20, with particular focus on the central nervous system autoimmune diseases multiple sclerosis and neuromyelitis optica. The principles and mechanisms herein discussed might also be relevant to a variety of other nervous system autoimmune disorders, including NMDA (N-methyl-D-aspartate) receptor encephalitis, transverse myelitis and myasthenia gravis.
机译:人们越来越认识到B细胞在适应性免疫应答中的作用,使B细胞成为自身免疫的重要治疗靶标。通过识别在B细胞上特异性表达的细胞表面蛋白,特别是CD19和CD20,目前的许多免疫疗法和发展中的免疫疗法都将B细胞作为目标来消除。这两种分子在功能和表达上的相似性和差异预示着靶向CD19和CD20的药物具有某些共同的,某些不同的药理作用,这可能导致此类药物在临床安全性和功效上的差异。在这里,我们回顾了CD19和CD20功能和生物学的当前知识,调查了针对这些分子的当前和发展疗法,并讨论了针对CD19和CD20的药物在消除B细胞方面的潜在差异,特别关注中枢神经系统自身免疫疾病多发性硬化症和视神经脊髓炎。本文讨论的原理和机制也可能与多种其他神经系统自身免疫性疾病有关,包括NMDA(N-甲基-D-天冬氨酸)受体脑炎,横贯性脊髓炎和重症肌无力。

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