Diagnostic and prognostic value of JC virus DNA in plasma in progressive multifocal leukoencephalopathy

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

JC Virus
Progressive Multifocal Leukoencephalopathy
HIV
DNA
Cerebrospinal Fluid
Disease Progression
Demyelinating Diseases
Immune System
Adrenal Cortex Hormones

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Diagnostic and prognostic value of JC virus DNA in plasma in progressive multifocal leukoencephalopathy. / Ferretti, Francesca; Bestetti, Arabella; Yiannoutsos, Constantin; Musick, Beverly S.; Gerevini, Simonetta; Passeri, Laura; Bossolasco, Simona; Boschini, Antonio; Franciotta, Diego; Lazzarin, Adriano; Cinque, Paola.

In: Clinical Infectious Diseases, Vol. 67, No. 1, 01.01.2018, p. 65-72.

Research output: Contribution to journalArticle

Ferretti, F, Bestetti, A, Yiannoutsos, C, Musick, BS, 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, vol. 67, no. 1, pp. 65-72. https://doi.org/10.1093/cid/ciy030
Ferretti, Francesca ; Bestetti, Arabella ; Yiannoutsos, Constantin ; Musick, Beverly S. ; Gerevini, Simonetta ; Passeri, Laura ; Bossolasco, Simona ; Boschini, Antonio ; Franciotta, Diego ; Lazzarin, Adriano ; Cinque, Paola. / Diagnostic and prognostic value of JC virus DNA in plasma in progressive multifocal leukoencephalopathy. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 1. pp. 65-72.
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abstract = "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.",
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AU - Ferretti, Francesca

AU - Bestetti, Arabella

AU - Yiannoutsos, Constantin

AU - Musick, Beverly S.

AU - Gerevini, Simonetta

AU - Passeri, Laura

AU - Bossolasco, Simona

AU - Boschini, Antonio

AU - Franciotta, Diego

AU - Lazzarin, Adriano

AU - Cinque, Paola

PY - 2018/1/1

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N2 - 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.

AB - 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.

KW - HIV

KW - JC virus

KW - Natalizumab

KW - Plasma JCV

KW - Progressive multifocal leukoencephalopathy

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