IRCSS San Raffaele Roma, Microbiology of Chronic Neuro-Degenerative Pathologies, 00163 Rome, Italy.
Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, 00185 Rome, Italy.
Viruses. 2021 Aug 25;13(9):1684. doi: 10.3390/v13091684.
Progressive multifocal leukoencephalopathy (PML) caused by the JC virus is the main limitation to the use of disease modifying therapies for treatment of multiple sclerosis (MS).
To assess the PML risk in course of ocrelizumab, urine and blood samples were collected from 42 MS patients at baseline (T0), at 6 (T2) and 12 months (T4) from the beginning of therapy. After JCPyV-DNA extraction, a quantitative-PCR (Q-PCR) was performed. Moreover, assessment of JCV-serostatus was obtained and arrangements' analysis of non-coding control region (NCCR) and of viral capsid protein 1 (VP1) was carried out.
Q-PCR revealed JCPyV-DNA in urine at all selected time points, while JCPyV-DNA was detected in plasma at T4. From T0 to T4, JC viral load in urine was detected, increased in two logarithms and, significantly higher, compared to viremia. NCCR from urine was archetypal. Plasmatic NCCR displayed deletion, duplication, and point mutations. VP1 showed the S269F substitution involving the receptor-binding region. Anti-JCV index and IgM titer were found to statistically decrease during ocrelizumab treatment.
Ocrelizumab in JCPyV-DNA positive patients is safe and did not determine PML cases. Combined monitoring of ocrelizumab's effects on JCPyV pathogenicity and on host immunity might offer a complete insight towards predicting PML risk.
由 JC 病毒引起的进行性多灶性白质脑炎（PML）是使用疾病修正疗法治疗多发性硬化症（MS）的主要限制因素。
为了评估奥瑞珠单抗治疗过程中的 PML 风险，在开始治疗后的 6（T2）和 12 个月（T4），从 42 名 MS 患者的基线（T0）采集尿液和血液样本。提取 JCPyV-DNA 后，进行定量 PCR（Q-PCR）。此外，还评估了 JCV 血清状态，并对非编码控制区（NCCR）和病毒衣壳蛋白 1（VP1）进行了分析。
Q-PCR 在所有选定的时间点均在尿液中检测到 JCPyV-DNA，而在 T4 时在血浆中检测到 JCPyV-DNA。从 T0 到 T4，尿液中检测到 JC 病毒载量，增加了两个对数，与病毒血症相比显著升高。尿液中的 NCCR 是典型的。血浆 NCCR 显示缺失、重复和点突变。VP1 显示涉及受体结合区的 S269F 取代。在奥瑞珠单抗治疗期间，抗 JCV 指数和 IgM 滴度被发现有统计学意义下降。
奥瑞珠单抗在 JCPyV-DNA 阳性患者中是安全的，不会导致 PML 病例。对奥瑞珠单抗对 JCPyV 致病性和宿主免疫的影响进行联合监测，可能为预测 PML 风险提供全面的见解。
