Institute for Neuroimmunology and Clinical MS Research, Center for Molecular Neurobiology Hamburg, University Medical Center-Eppendorf, Hamburg, UKE, Germany.
Eur J Immunol. 2012 Mar;42(3):790-8. doi: 10.1002/eji.201142108. Epub 2011 Dec 27.
Natalizumab, an antibody against the α4 subunit of α4 integrins, has been approved for multiple sclerosis (MS) therapy based on its high efficacy and safety profile. However, natalizumab has been associated with the development of progressive multifocal leukoencephalopathy (PML), a disorder caused by JC virus (JCV) infection. In order to improve our understanding of the mechanism of action of natalizumab and to identify possible risk factors for PML development, we have characterized in detail the cell blood composition in MS patients treated with natalizumab for more than 30 months. Natalizumab induced the release of lymphoid- but not myeloid precursor cells, which resulted in a chronic increase ofT-, NK- and particularly B cells. While the percentage of recent thymic emigrants (RTEs), naϊve, effector or memory T cells remained unchanged during treatment, a higher percentage of memory- and marginal zone (MZ)-like, but not of naϊve B cells, was observed, which most likely is due to a decreased retention of these cells within the splenic MZ. The ability of natalizumab to influence B-cell migration and homeostasis through the splenic MZ, where JCV has been detected, adds to the list of natalizumab effects and may contribute to PML development by disseminating JCV.
那他珠单抗是一种针对 α4 整合素 α4 亚基的抗体，因其高效和安全的特性已被批准用于多发性硬化症（MS）的治疗。然而，那他珠单抗与进行性多灶性白质脑病（PML）的发生有关，这是一种由 JC 病毒（JCV）感染引起的疾病。为了更好地了解那他珠单抗的作用机制，并确定 PML 发展的可能危险因素，我们详细研究了接受那他珠单抗治疗超过 30 个月的 MS 患者的血液细胞组成。那他珠单抗诱导淋巴样但不髓样祖细胞的释放，导致 T 细胞、NK 细胞和特别是 B 细胞的慢性增加。虽然治疗过程中最近胸腺迁出细胞（RTEs）、幼稚、效应或记忆 T 细胞的百分比保持不变，但观察到更多的记忆和边缘区（MZ）样 B 细胞，而不是幼稚 B 细胞，这很可能是由于这些细胞在脾脏 MZ 中的保留减少所致。那他珠单抗通过脾脏 MZ 影响 B 细胞迁移和稳态的能力，增加了那他珠单抗的作用列表，并可能通过传播 JCV 导致 PML 的发生。
