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Assessment of the risk of polyomavirus JC reactivation in patients with immune-mediated diseases during long-term treatment with infliximab

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Abstract

Polyomavirus JC (JCV) reactivation causing progressive multifocal leukoencephalopathy is a main concern during biological therapies. Here, JCV reactivation in patients suffering from immune-mediated diseases after a long-term treatment with anti-tumor necrosis factor alpha (TNF-α) inhibitor infliximab was investigated. Peripheral mononuclear blood cells (PBMC), plasma and urine samples were obtained from 61 immune-mediated diseases patients treated or not with infliximab in combination with steroid and other immunomodulators and from 20 healthy donors. JCV DNA was transiently detected in 12 PBMC of 40 patients at different doses of infliximab with a higher prevalence than that of the 21 patients untreated. Conversely, a stable JCV positivity in urine of treated and untreated patients was detected. Sequencing the noncoding control region (NCCR), all samples exhibited the archetype structure with few mutations in transcriptional factor binding regions. The consequence of anti-TNF-α treatment on viral persistence was examined monitoring Torquetenovirus viremia and investigating the TNF-α-induced microRNA regulators of transcriptional factors, with a binding site on NCCR. Although infliximab treatment in this study did not affect directly JCV reactivation, further investigation on host factor(s) regulated by it will be of warranty in the understanding the mechanism(s) that may affect viral persistence.

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Acknowledgement

This study was supported by grants from Ministero della Universita e Ricerca Tecnologica, Rome, Italy (PRIN project 2007 ACZMMZ_004).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Virology Unit, Department of Public Health, University of Florence, Florence, Italy

    Simone Giannecchini, Valeria Clausi, Francesco Martelli & Alberta Azzi

  2. Department of Biomedicine, Immunoallergology Unit, Policlinico di Careggi, AOU Careggi, Florence, Italy

    Alessandra Vultaggio & Andrea Matucci

  3. Center for Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy

    Enrico Maggi

  4. Virology Unit, Pisa University Hospital, University of Pisa, Pisa, Italy

    Lisa Macera & Fabrizio Maggi

  5. Department of Experimental Pathology, Virology Section and Retrovirus Centre, University of Pisa, Pisa, Italy

    Lisa Macera & Fabrizio Maggi

  6. Dipartimento di Sanità Pubblica, Università di Firenze, Viale Morgagni 48, 50134, Florence, Italy

    Simone Giannecchini

Authors
  1. Simone Giannecchini
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  2. Valeria Clausi
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  3. Alessandra Vultaggio
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  4. Lisa Macera
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  5. Fabrizio Maggi
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  6. Francesco Martelli
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  7. Alberta Azzi
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  8. Enrico Maggi
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  9. Andrea Matucci
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Corresponding author

Correspondence to Simone Giannecchini.

Additional information

S. Giannecchini and V. Clausi contributed equally to the work and share first authorship.

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Giannecchini, S., Clausi, V., Vultaggio, A. et al. Assessment of the risk of polyomavirus JC reactivation in patients with immune-mediated diseases during long-term treatment with infliximab. J. Neurovirol. 18, 55–61 (2012). https://doi.org/10.1007/s13365-012-0078-1

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  • DOI: https://doi.org/10.1007/s13365-012-0078-1

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