Department of Neurology, University Medical Center, 37075 Göttingen, Germany.
Institute for Neuropathology, University Medical Center, 37075 Göttingen, Germany.
Int J Mol Sci. 2020 Jul 16;21(14):5021. doi: 10.3390/ijms21145021.
B cells are considered major contributors to multiple sclerosis (MS) pathophysiology. While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells. Here, we review the current understanding how approved MS medications affect peripheral B lymphocytes in humans. These highly contrasting effects are of substantial importance when considering these drugs as therapy for neuromyelitis optica spectrum disorders (NMOSD), a frequent differential diagnosis to MS, which is considered being a primarily B cell- and antibody-driven diseases. Data indicates that MS medications, which deplete B cells or induce an anti-inflammatory phenotype of the remaining ones, were effective and safe in aquaporin-4 antibody positive NMOSD. In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.
B 细胞被认为是多发性硬化症 (MS) 病理生理学的主要贡献者。虽然最近批准的疾病修正药物，如奥瑞珠单抗，可以直接耗尽 B 细胞，但大多数 MS 药物并非主要设计用于靶向 B 细胞。在这里，我们回顾了目前对已批准的 MS 药物如何影响人类外周 B 淋巴细胞的理解。当考虑这些药物作为视神经脊髓炎谱系疾病 (NMOSD) 的治疗方法时，这些高度对比的效果非常重要，NMOSD 是 MS 的常见鉴别诊断，被认为是主要由 B 细胞和抗体驱动的疾病。数据表明，在水通道蛋白 4 抗体阳性 NMOSD 中，耗竭 B 细胞或诱导剩余 B 细胞产生抗炎表型的 MS 药物是有效且安全的。相比之下，如那他珠单抗和干扰素-β等导致外周血中 B 细胞激活和积累的药物，在 NMOSD 中缺乏疗效，甚至会引发灾难性的疾病活动。因此，我们得出结论，MS 药物对 B 细胞的不同作用是决定抗体依赖性疾病（如血清阳性 NMOSD）治疗效果或失败的一个潜在参数。
