JC virus reactivation during prolonged natalizumab monotherapy for MS


Treatment, therapies and management:

Forty three JCV-seropositive MS patients were included in this study with 32 on natalizumab therapy for >18 months, six on interferon β-1a monotherapy >36 months and five untreated controls. CSF, blood and urine for JCV DNA was tested using QPCR.
JCV-specific T-cell responses were determined using enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays.

JCV DNA was detected in the CSF of 7.4% of natalizumab-treated MS patients. These patients did not have symptoms or MRI lesions in keeping with progressive multifocal leukoencephalopathy (PML). JCV DNA was detected in blood in 27.9% of subjects and in urine in 25.6% of subjects, with no difference between natalizumab-treated patients and controls. CD34+ cells and monocytes had higher JC viral load when compared to other subpopulations of cells.

They found that intracellular cytokine staining was more sensitive than ELISpot. JCV-specific CD4+ T-cells were detected more frequently in MS patients with JCV DNA in CD34+ and B cells.

Overall, this shows that PCR detection of JCV DNA in CSF after an extended natalizumab course, in the absence of new clinical or MRI findings, is not equivalent to PML.  We need to further improve our understanding of the pathogenesis of JCV reactivation and improve PML risk strategies.


Authors:
Chalkias S, Dang X
Source: Ann Neurol. 2014 Mar 31. doi: 10.1002/ana.24148. [Epub ahead of print]
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