Invited article: Inhibition of B cell functions - Implications for neurology
Invited article: Inhibition of B cell functions - Implications for neurology
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DOI：
10.1212/01.wnl.0000313840.27060.bf
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发表时间：
2008-06-03
期刊：
影响因子：
9.9
通讯作者：
Dalakas, Marinos C.
中科院分区：
文献类型：
--
作者：
Dalakas, Marinos C.
B细胞参与许多神经系统疾病的病理生理学，通过产生自身抗体、细胞因子分泌或通过充当导致T细胞活化的抗原呈递细胞而起致病或促进作用。B细胞在各种CNS病症中克隆扩增，例如多发性硬化（MS）、副肿瘤性CNS病症或僵人综合征，并且在脱髓鞘性神经病和肌无力中被激活以产生致病性自身抗体。B细胞活化因子（BAFF）和增殖诱导配体（APRIL）是B细胞存活的关键细胞因子，在MS脑和炎性肌病的肌肉中强烈不受调节。使用一系列针对CD 20 + B细胞的单克隆抗体或增加B细胞存活的分子（例如BAFF/APRIL及其受体BAFF-R、TACI和BCMA）调节B细胞功能提供了治疗上述神经系统疾病的合理方法。在对照研究中，利妥昔单抗，一种B细胞耗竭单克隆抗体，在MS和副蛋白血症抗MAG脱髓鞘神经病中一直令人鼓舞，发挥持久的缓解作用。在非对照系列中，已报告在几种疾病中获益。B细胞耗竭是目前在治疗几种自身免疫性神经系统疾病中探索的耐受性良好的治疗选择。
B cells are involved in the pathophysiology of many neurologic diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. B cells are clonally expanded in various CNS disorders, such as multiple sclerosis (MS), paraneoplastic CNS disorders, or stiff-person syndrome, and are activated to produce pathogenic autoantibodies in demyelinating neuropathies and myasthenia. B cell activating factor (BAFF) and a proliferating inducing ligand (APRIL), key cytokines for B cell survival, are strongly unregulated in MS brain and in muscles of inflammatory myopathies. Modulation of B cell functions using a series of monoclonal antibodies against CD20 + B cells or the molecules that increase B cell survival, such as BAFF/APRIL and their receptors BAFF-R, TACI, and BCMA, provide a rational approach to the treatment of the aforementioned neurologic disorders. In controlled studies, rituximab, a B cell-depleting monoclonal antibody, has been encouraging in MS and paraproteinemic anti-MAG demyelinating neuropathy, exerting long-lasting remissions. In uncontrolled series, benefit has been reported in several disorders. B cell depletion is a well-tolerated therapeutic option currently explored in the treatment of several autoimmune neurologic disorders.