Marzocchetti A, Tompkins T, Clifford D B, Gandhi R T, Kesari S, Berger J R, Simpson D M, Prosperi M, De Luca A, Koralnik I J
Division of Viral Pathogenesis, BIDMC, Harvard Medical School, Boston, MA 02215, USA.
Neurology. 2009 Nov 10;73(19):1551-8. doi: 10.1212/WNL.0b013e3181c0d4a1.
We sought to characterize the role of immunologic, virologic, and radiologic determinants of survival in patients with progressive multifocal leukoencephalopathy (PML).
We recorded the clinical outcome of 60 patients with PML (73% HIV+) who were prospectively evaluated between 2000 and 2007 for the presence of JC virus (JCV)-specific CD8+ cytotoxic T-lymphocytes (CTL) in blood.
Estimated probability of survival at 1 year was 52% for HIV+/PML and 58% for HIV- patients with PML. Patients with PML with detectable CTL within 3 months of diagnosis had a 1-year estimated survival of 73% compared to 46% for those without CTL (hazard ratio [HR] for death = 0.47, 95% confidence interval [CI] 0.13-1.75, p = 0.26). Patients with CTL response had an increased likelihood of having contrast enhancement of PML lesions and immune reconstitution inflammatory syndrome (odds ratio 3.7 and 7.8). Estimated 1-year survival was 48% in HIV+ patients with PML with CD4 count <200/microL at PML diagnosis compared to 67% in those with CD4 >200/microL (HR for death 1.41, 95% CI 0.27-7.38, p = 0.68). JCV DNA was detected in the urine of 48% and in the blood of 56% of patients with PML, but viruria and viremia were not associated with survival.
The presence of JC virus (JCV)-specific cytotoxic T-lymphocytes (CTL) was associated with a trend toward longer survival in patients with progressive multifocal leukoencephalopathy (PML), which was more pronounced than the impact of CD4 count in HIV+ patients with PML early after diagnosis. Despite the association of contrast enhancement and immune reconstitution inflammatory syndrome with JCV-specific CTL, these cannot be considered as surrogate markers for the prognostic value of the CTL. Strategies aiming at improving the cellular immune response may improve the course of PML.
我们试图明确免疫、病毒学及影像学因素在进行性多灶性白质脑病（PML）患者生存中的作用。
我们记录了60例PML患者（73%为HIV阳性）的临床结局，这些患者于2000年至2007年间接受前瞻性评估，检测血液中是否存在JC病毒（JCV）特异性CD8 + 细胞毒性T淋巴细胞（CTL）。
HIV阳性/PML患者1年生存率估计为52%，HIV阴性PML患者为58%。诊断后3个月内可检测到CTL的PML患者1年生存率估计为73%，而未检测到CTL的患者为46%（死亡风险比[HR] = 0.47，95%置信区间[CI] 0.13 - 1.75，p = 0.26）。有CTL反应的患者PML病灶出现对比增强及免疫重建炎症综合征的可能性增加（优势比分别为3.7和7.8）。PML诊断时CD4计数<200/μL的HIV阳性PML患者1年生存率估计为48%，而CD4>200/μL的患者为67%（死亡HR为1.41，95% CI 0.27 - 7.38，p = 0.68）。48%的PML患者尿液中检测到JCV DNA，56%的患者血液中检测到，但病毒尿和病毒血症与生存无关。
JC病毒（JCV）特异性细胞毒性T淋巴细胞（CTL）的存在与进行性多灶性白质脑病（PML）患者生存时间延长的趋势相关，这一关联在诊断早期比HIV阳性PML患者的CD4计数影响更为明显。尽管对比增强和免疫重建炎症综合征与JCV特异性CTL相关，但这些不能被视为CTL预后价值的替代标志物。旨在改善细胞免疫反应的策略可能改善PML的病程。
