Department of Neuroscience, Multiple Sclerosis Centre, First Clinic of Neurology, University Hospital of Padova, Padova, Italy.
J Neurol Neurosurg Psychiatry. 2010 Dec;81(12):1345-50. doi: 10.1136/jnnp.2009.201079. Epub 2010 Jun 14.
Natalizumab, used as therapy for multiple sclerosis (MS), has been associated with progressive multifocal leucoencephalopathy (PML), a potentially fatal disease caused by JC virus (JCV), which is not predictable by specific markers. This study evaluated whether JCV reactivation occurred in the urine and/or plasma in 42 MS patients treated with natalizumab over 18 months, and followed by a thorough monitoring programme.
42 patients (F/M: 24/18, mean age 34.4±8.9 years) were followed-up by: urine and plasma JCV-DNA PCR assay, immune cell subsets analysis, clinical and MRI evaluation, quality of life, fatigue and mood assessment.
JCV data. At baseline, 11/42 (26%) patients had JCV viruria, persistent at serial controls. One patient acquired viruria at month 1 and one patient at month 12. No patient had JCV viraemia at baseline; three patients acquired viraemic (one at month 6, one at month 13 (both transiently) and one at month 12 (persistently viraemic)). The prevalence of JCV in both urine and plasma did not change significantly from baseline to months 12 and 18. No patient had clinical or MRI evidence of PML. Immunological data. Circulating B cells showed greater expansion (300% increase in absolute number) since the first infusion. NK cell count doubled with no change in percentage while T cell count increased with a reduced percentage, reflecting a clear redistribution in the lymphocyte compartment. CD4+ and CD8+ T cells increased proportionally, with no change in their percentage. Clinical data. 27 patients (64%) were disease free after 1 year. A marked improvement in quality of life was reported by 72% of patients.
No evidence of subclinical JCV reactivation was found in our natalizumab treated MS patients up to 18 months of therapy, notwithstanding the marked increase in circulating B cells observed. Moreover, the efficacy of natalizumab, its tolerability and the positive impact on quality of life were confirmed in this study.
那他珠单抗被用于多发性硬化症（MS）的治疗，与进行性多灶性白质脑病（PML）相关，这是一种由 JC 病毒（JCV）引起的潜在致命疾病，目前无法通过特定标志物进行预测。本研究评估了在接受那他珠单抗治疗 18 个月的 42 名 MS 患者中，尿液和/或血浆中是否存在 JCV 再激活，并通过彻底的监测方案进行随访。
42 名患者（男/女：24/18，平均年龄 34.4±8.9 岁）接受了以下随访：尿液和血浆 JCV-DNA PCR 检测、免疫细胞亚群分析、临床和 MRI 评估、生活质量、疲劳和情绪评估。
JCV 数据。基线时，11/42（26%）名患者存在 JCV 尿病毒血症，且在连续监测中持续存在。1 名患者在第 1 个月时出现尿病毒血症，1 名患者在第 12 个月时出现。基线时无患者存在 JCV 血症；3 名患者出现血症（1 名在第 6 个月，1 名在第 13 个月（均为一过性），1 名在第 12 个月（持续性血症））。从基线到第 12 个月和第 18 个月，尿液和血浆中 JCV 的患病率均无显著变化。无患者出现 PML 的临床或 MRI 证据。免疫学数据。自首次输注以来，循环 B 细胞的扩增更为显著（绝对数量增加 300%）。NK 细胞计数增加了一倍，而百分比不变，而 T 细胞计数增加，百分比降低，反映了淋巴细胞分布的明显再分布。CD4+和 CD8+T 细胞按比例增加，其百分比无变化。临床数据。1 年后，27 名（64%）患者无疾病进展。72%的患者报告生活质量有明显改善。
在接受那他珠单抗治疗的 MS 患者中，未发现亚临床 JCV 再激活的证据，尽管观察到循环 B 细胞显著增加。此外，本研究证实了那他珠单抗的疗效、耐受性和对生活质量的积极影响。
