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

Francesca Ferretti, Arabella Bestetti, Constantin T Yiannoutsos, Beverly S Musick, Simonetta Gerevini, Laura Passeri, Simona Bossolasco, Antonio Boschini, Diego Franciotta, Adriano Lazzarin, Paola Cinque

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)65-72
Number of pages7
JournalClinical Infectious Diseases
Early online dateJan 15 2018
DOIs
Publication statusPublished - Jun 30 2018

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