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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Ann+Neurol 2014 ; 75 (6): 925-34 Nephropedia Template TP
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JC virus Reactivation During Prolonged Natalizumab Monotherapy for Multiple Sclerosis #MMPMID24687904
Ann Neurol 2014[Jun]; 75 (6): 925-34 PMID24687904show ga
Objective: To determine the prevalence of JC virus (JCV) reactivation and JCV-specific cellular immune response during prolonged natalizumab treatment for multiple sclerosis (MS). Methods: We enrolled 43 JCV-seropositive MS patients, including 32 on natalizumab monotherapy>18 months, 6 on interferon ?-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. Results: 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). Interpretation: 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.