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

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5 Scopus citations


Background. Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by the polyomavirus JC (John Cunningham; JCV) that affects patients with impaired immune systems. While JCV-DNA detection in cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of plasma JCV-DNA is uncertain. Methods. We retrospectively analyzed plasma samples from PML patients that were drawn close to disease onset and from controls without PML. In PML patients, we compared plasma JCV-DNA detection and levels to clinical and laboratory parameters, and patient survival. Results. JCV-DNA was detected in plasma of 49/103 (48%) patients with PML (20/24, 83%, human immunodeficiency virus [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 48% and 97% (83% and 100% in HIV-negative; 37% and 92% in HIV-positive), respectively. Among 16 PML patients with undetectable CSF JCV-DNA, 4 (25%) had detectable plasma JCV-DNA. Plasma JCV-DNA levels were independently associated with CSF levels (P < .0001) and previous corticosteroid treatment (P = .012). Higher plasma JCV-DNA levels were associated with disease progression in HIV-negative patients (P = .005); in HIV-positive patients, there was an increased risk of progression only in those treated with combination antiretroviral therapy (cART; P < .0001). Conclusions. Testing JCV-DNA in plasma 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 (US)
Pages (from-to)65-72
Number of pages8
JournalClinical Infectious Diseases
Issue number1
StatePublished - Jan 1 2018


  • HIV
  • JC virus
  • Natalizumab
  • Plasma JCV
  • Progressive multifocal leukoencephalopathy

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Ferretti, F., Bestetti, A., Yiannoutsos, C. T., Musick, B. S., Gerevini, S., Passeri, L., Bossolasco, S., Boschini, A., Franciotta, D., Lazzarin, A., & Cinque, P. (2018). Diagnostic and prognostic value of JC virus DNA in plasma in progressive multifocal leukoencephalopathy. Clinical Infectious Diseases, 67(1), 65-72. https://doi.org/10.1093/cid/ciy030