B lymphocytes in neuromyelitis optica.
B lymphocytes in neuromyelitis optica.
复制标题
b淋巴细胞神经霉炎。
DOI：
10.1212/nxi.0000000000000104
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Stadelmann C
中科院分区：
文献类型：
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作者：
Bennett JL;O'Connor KC;Bar-Or A;Zamvil SS;Hemmer B;Tedder TF;von Büdingen HC;Stuve O;Yeaman MR;Smith TJ;Stadelmann C
视神经脊髓炎 (NMO) 是一种中枢神经系统炎症性自身免疫性疾病，主要影响脊髓和视神经。大多数（约 75%）NMO 患者的星形胶质细胞水通道水通道蛋白 4 (AQP4) 自身抗体呈血清阳性。这些自身抗体主要是 IgG1，大量证据支持其致病性，可能是通过与 CNS 星形胶质细胞上的 AQP4 结合，导致星形胶质细胞损伤和炎症。综合临床和实验室研究表明，B 细胞在 NMO 免疫病理学中发挥着重要作用。已假设多种机制：AQP4自身抗体产生、促炎B细胞和浆母细胞活性增强、B细胞耐受检查点异常、B细胞调节功能减弱以及B细胞无反应性丧失。因此，目前许多 NMO 标签外疗法都会消耗 B 细胞或调节其活性。了解 B 细胞在疾病活动的起始、维持和传播中的作用和机制对于增进我们对 NMO 发病机制的理解和开发有效的疾病特异性疗法非常重要。
Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that predominantly affects the spinal cord and optic nerves. A majority (approximately 75%) of patients with NMO are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 (AQP4). These autoantibodies are predominantly IgG1, and considerable evidence supports their pathogenicity, presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury and inflammation. Convergent clinical and laboratory-based investigations have indicated that B cells play a fundamental role in NMO immunopathology. Multiple mechanisms have been hypothesized: AQP4 autoantibody production, enhanced proinflammatory B cell and plasmablast activity, aberrant B cell tolerance checkpoints, diminished B cell regulatory function, and loss of B cell anergy. Accordingly, many current off-label therapies for NMO deplete B cells or modulate their activity. Understanding the role and mechanisms whereby B cells contribute to initiation, maintenance, and propagation of disease activity is important to advancing our understanding of NMO pathogenesis and developing effective disease-specific therapies.