JC virus reactivation during prolonged natalizumab monotherapy for multiple sclerosis.
JC virus reactivation during prolonged natalizumab monotherapy for multiple sclerosis.
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DOI：
10.1002/ana.24148
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发表时间：
2014-06
影响因子：
11.2
通讯作者：
Koralnik, Igor J.
中科院分区：
文献类型：
--
作者：
Chalkias, Spyridon;Dang, Xin;Bord, Evelyn;Stein, Marion C.;Kinkel, R. Philip;Sloane, Jacob A.;Donnelly, Maureen;Ionete, Carolina;Houtchens, Maria K.;Buckle, Guy J.;Batson, Stephanie;Koralnik, Igor J.
确定在多发性硬化（MS）的长期那他珠单抗治疗期间JC病毒（JCV）再活化和JCV特异性细胞免疫应答的发生率。我们招募了43名JCV血清阳性MS患者，包括32名接受那他珠单抗单药治疗>18个月，6名接受干扰素β-1a单药治疗>36个月，5名未接受治疗的对照。我们在脑脊液（CSF）、血液和尿液中进行了JCV DNA的QPCR，并且我们使用酶联免疫吸附斑点（ELISpot）和细胞内细胞因子染色（ICS）测定，离体和用JCV肽体外刺激后测定了JCV特异性T细胞应答。在2/27例（7.4%）接受那他珠单抗治疗的MS患者的CSF中检测到JCV DNA，这些患者没有与进行性多灶性白质脑病一致的症状或MRI病变。在12/43例（27.9%）受试者的血液和11/43例（25.6%）受试者的尿液中检测到JCV DNA，在那他珠单抗治疗患者和对照组之间无差异。与其他亚群相比，CD 34+细胞和单核细胞中的JC病毒载量较高。ICS比ELISpot更敏感，并且在体外刺激后更频繁地检测到由CD 4+和CD 8 + T淋巴细胞介导的JCV特异性T细胞应答。在MS患者中，在CD 34+（p=0.05）和B细胞（p=0.03）中检测到JCV特异性CD 4 + T细胞的频率更高。接受那他珠单抗治疗的MS患者的CSF中可能发生无症状JCV再激活。与其他单核细胞相比，循环CD 34+细胞和单核细胞中的JCV DNA负荷更高，血液中的JCV可能触发JCV特异性CD 4 + T细胞应答。JCV特异性细胞免疫应答在所有JCV血清阳性MS患者中非常普遍，无论治疗如何。
To determine the prevalence of JC virus (JCV) reactivation and JCV-specific cellular immune response during prolonged natalizumab treatment for multiple sclerosis (MS). We enrolled 43 JCV-seropositive MS patients, including 32 on natalizumab monotherapy>18 months, 6 on interferon β-1a monotherapy>36 months and 5 untreated controls. We performed QPCR in cerebrospinal fluid (CSF), blood and urine for JCV DNA and we determined JCV-specific T cell responses using enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays, ex vivo and after in vitro stimulation with JCV peptides. JCV DNA was detected in the CSF of 2/27 (7.4%) natalizumab-treated MS patients who had no symptoms or MRI lesions consistent with progressive multifocal leukoencephalopathy. JCV DNA was detected in blood of 12/43 (27.9%) and in urine of 11/43 (25.6%) subjects without difference between natalizumab-treated patients and controls. JC viral load was higher in CD34+ cells and in monocytes compared to other subpopulations. ICS was more sensitive than ELISpot, and JCV-specific T cell responses, mediated by both CD4+ and CD8+ T-lymphocytes, were detected more frequently after in vitro stimulation. JCV-specific CD4+ T-cells were detected ex vivo more frequently in MS patients with JCV DNA in CD34+ (p=0.05) and B cells (p=0.03). Asymptomatic JCV reactivation may occur in CSF of natalizumab-treated MS patients. JCV DNA load is higher in circulating CD34+ cells and monocytes compared to other mononuclear cells, and JCV in blood might trigger a JCV-specific CD4+ T-cell response. JCV-specific cellular immune response is highly prevalent in all JCV-seropositive MS patients, regardless of treatment.
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DOI：
10.1177/1352458508096870
发表时间：
2009-01
期刊：
Multiple sclerosis (Houndmills, Basingstoke, England)
影响因子：
--
作者：
Iacobaeus E;Ryschkewitsch C;Gravell M;Khademi M;Wallstrom E;Olsson T;Brundin L;Major E
通讯作者：
Major E
影响因子：
6.4
作者：
Chapagain, Moti L.;Nerurkar, Vivek R.
通讯作者：
Nerurkar, Vivek R.
影响因子：
3.2
作者：
Dörries, K;Sbiera, S;Dörries, R
通讯作者：
Dörries, R
影响因子：
5.4
作者：
Monaco, MCG;Atwood, WJ;Major, EO
通讯作者：
Major, EO
影响因子：
1.4
作者：
Fragoso, Yara Dadalti;Mendes, Maria Fernanda;Satomi, Massaco
通讯作者：
Satomi, Massaco