title: Urinary JCV-DNA testing during natalizumab treatment may increase accuracy of PML risk stratification.
abstract: The risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab for multiple sclerosis (MS) is a serious concern. The presence of anti-JC virus antibodies is a risk factor for PML development, but 2.5 % of the patients result falsely-negative, while the prognostic relevance of testing JCV-DNA in biological fluids of treated patients is debated. Aim of this work was to evaluate the utility of testing JCV-DNA, together with anti-JCV antibodies, in biological samples of treated patients as a tool for PML risk stratification. 126 subjects from 5 MS Centers in Italy were included in the study. We performed a cross-sectional study in 63 patients testing JCV-DNA in blood, peripheral blood cells and urine. We longitudinally assessed the presence of JCV-DNA in a cohort of 33 subjects, one of which developed PML. We could test retrospectively serum samples from another PML case occurred during natalizumab therapy. Anti-JCV antibodies and urinary JCV-DNA were both tested in 73 patients. No changes in JCV-DNA status occurred during natalizumab treatment. The subject who developed PML in the longitudinal cohort had detectable JCV-DNA in urine at all time-points while serum or blood from both PML patients were always negative before the onset of disease and, in one case, after. Four subjects with JCV-DNA in urine and undetectable anti-JCV antibodies were retested for anti-JCV antibodies and three out of four resulted positive. In conclusion, testing JCV-DNA in urine is complementary to testing anti-JCV antibodies in identifying patients at risk of PML.
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Via De Toni 5, 16132, Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Laroni
authors.forename: C G
authors.initials: CG
authors.lastname: Giacomazzi
authors.forename: L
authors.initials: L
authors.lastname: Grimaldi
authors.forename: P
authors.initials: P
authors.lastname: Gallo
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.forename: A
authors.initials: A
authors.lastname: Bertolotto
authors.forename: J L
authors.initials: JL
authors.lastname: McDermott
authors.forename: I
authors.initials: I
authors.lastname: Gandoglia
authors.forename: I
authors.initials: I
authors.lastname: Martini
authors.forename: G
authors.initials: G
authors.lastname: Vitello
authors.forename: F
authors.initials: F
authors.lastname: Rinaldi
authors.forename: L
authors.initials: L
authors.lastname: Barzon
authors.forename: V
authors.initials: V
authors.lastname: Militello
authors.forename: M
authors.initials: M
authors.lastname: Pizzorno
authors.forename: F
authors.initials: F
authors.lastname: Bandini
authors.forename: E
authors.initials: E
authors.lastname: Capello
authors.forename: G
authors.initials: G
authors.lastname: Palù
authors.forename: A
authors.initials: A
authors.lastname: Uccelli
authors.forename: G L
authors.initials: GL
authors.lastname: Mancardi
authors.forename: O E
authors.initials: OE
authors.lastname: Varnier
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000652:urine*; D003955:Diagnostic Tests, Routine; D005260:Female; D006801:Humans; D007577:JC Virus / Q000378:metabolism*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis* / Q000188:drug therapy / Q000652:urine*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D004279:DNA, Viral; D000069442:Natalizumab