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JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients

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Abstract

The risk of developing progressive multifocal leukoencephalopathy (PML), as a consequence of infection/reactivation with JC virus (JCV), is consistent in natalizumab-treated multiple sclerosis (MS) patients, with 430 cases of PML reported so far. The risk of PML is higher in JCV seropositive patients, and it is recommended that only MS patients without JCV antibodies should be enrolled in the treatment postulating that they do not have JCV infection.

We have studied forty-two natalizumab-treated MS patients, and urine and blood were collected monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified using quantitative real-time PCR assays, and serum anti-JCV antibodies were measured with the Stratify and/or Stratify DxSelect tests.

JCV and BKV DNA were not found in the blood samples, whereas they were found at least once in the urine of 21 of 42 (50 %) and of 25/42 (59.5 %) patients, respectively. JCV DNA urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and the effect of time was significant for JCV (p = 0.04), but not for BKV (p = 0.39). JCV viruria and seropositivity did not completely correlate, since three patients shedding JCV DNA in the urine were seronegative according to the serological tests.

The results indicated that natalizumab therapy may increase the rate of JCV urinary shedding. Additionally, we confirmed that the identification of JCV carriers cannot solely rely on serological tests, but sensitive methods for viral DNA detection should be adopted to more precisely identify the truly JCV uninfected cases.

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Acknowledgments

We would like to thank Dr. Federico Ambrogi from the University of Milano, Italy, for helping with the statistical analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding statement

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Department of Biomedical Surgical and Dental Sciences, University of Milano, Via Pascal, 36, Milan, 20133, Italy

    Serena Delbue, Camilla Carloni, Valentina Pecchenini, Lucia Signorini, Silvia Carluccio & Pasquale Ferrante

  2. Laboratory of Translational Research Fondazione Ettore Sansavini, Lugo, Italy

    Francesca Elia

  3. Department of General Neurology, National Neurological Institute C. Mondino, Pavia, Italy

    Diego Franciotta, Matteo Gastaldi, Elena Colombo & Roberto Bergamaschi

  4. Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy

    Anna Bellizzi

  5. Istituto Clinico Città Studi, Milan, Italy

    Pasquale Ferrante

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  1. Serena Delbue
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  2. Francesca Elia
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  3. Camilla Carloni
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Correspondence to Pasquale Ferrante.

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Delbue, S., Elia, F., Carloni, C. et al. JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients. J. Neurovirol. 21, 645–652 (2015). https://doi.org/10.1007/s13365-014-0268-0

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  • DOI: https://doi.org/10.1007/s13365-014-0268-0

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