Diagnostic and prognostic value of JC virus DNA in plasma in Progressive Multifocal Leukoencephalopathy

Abstract

Background

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by the polyomavirus JC (JCV) affecting subjects with impaired immune system. While JCV-DNA detection in cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of plasma JCV-DNA is still uncertain.

Methods

We retrospectively analyzed plasma samples drawn from patients with PML close to disease onset, and controls without PML. In PML patients, we compared plasma JCV DNA detection and levels to: JCV DNA in the other biological samples, clinical and laboratory parameters and patients' survival.

Results

JCV-DNA was detected in plasma of 49/103 (48%) patients with PML (20/24, 83%, HIV-negative; 29/79, 37%, HIV-positive) and of 4/144 (3%) controls without PML (0/95 HIV-negative; 4/49, 8%, HIV-positive), yielding a diagnostic sensitivity and specificity of, respectively, 48% and 97% (83% and 100% in HIV-negative; 37% and 92% in HIV-positive). Among 16 PML patients with undetectable CSF JCV-DNA, 4 (25%) had detectable plasma JCV-DNA. Plasma JCV-DNA levels were independently associated with those in the CSF (p<0.0001) and previous corticosteroid treatment (p=0.012). Higher plasma JCV-DNA levels were associated with disease progression in HIV-negative patients (p=0.005), while among HIV-positive patients, they identified an increased risk of progression only in those treated with combined antiretroviral thearapy (cART)(p<0.0001).

Conclusions

Testing JCV-DNA on plasma samples might complement PML diagnosis, especially when CSF is unavailable or JCV-DNA not detectable in CSF. In addition, JCV-DNA plasma levels could be useful as a marker of disease progression in both HIV-negative and cART-treated HIV-positive PML patients.