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Polyomavirus JC reactivation and noncoding control region sequence analysis in pediatric Crohn's disease patients treated with infliximab

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Abstract

The recent introduction of monoclonal antibodies in Crohn's disease (CD) management has been associated with the development of serious complications, such as the progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus (JCV) reactivation. Therefore, the aims of our study have been the investigation of the possible JCV reactivation in pediatric CD patients treated or not with infliximab, performing quantitative PCR in urine, plasma, and intestinal biopsies at the time of recruitment (t0) and every 4 months in 1 year of follow-up (t1, t2, and t3), and the analysis of the JCV noncoding control region (NCCR) to detect cellular transcription factors binding site mutations. Results obtained showed that, in urine and ileal specimens, JCV load significantly increased in infliximab-treated patients after 1 year of treatment (t3), while viremia was significantly higher at t1. JCV NCCR sequence analysis showed a structure similar to CY archetype in 65/80 analyzed sequences, but the remaining 15/80, obtained exclusively from plasma and biopsies, evidenced a CY NCCR organization with two recurrent nucleotide changes, the 37-T to G transversion in box A Spi-B binding site and the 217-G to A transition in box F, and a box D deletion. These rearrangements were always found at t3 within seven infliximab-treated CD patients, who presented a very severe disease at t0. We can conclude that our rearranged NCCR sequences could be considered a marker of JCV virulence during mAb treatment, although none of our examined patients developed PML, and further studies on a larger cohort of patients should be performed.

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Acknowledgments

This work was supported by MIUR grant. The excellent statistical assistance of Prof. J.F. Osborn is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Health Sciences and Infectious Diseases, “Sapienza” University, P.le Aldo Moro, 5, 00185, Rome, Italy

    Anna Bellizzi, Elena Anzivino, Maria Teresa Colosimo, Monica Mischitelli, Fernanda Chiarini & Valeria Pietropaolo

  2. Department of Pediatrics, “Sapienza” University, Rome, Italy

    Federica Ferrari, Giovanni Di Nardo & Salvatore Cucchiara

  3. National Institute for Infectious Diseases “Lazzaro Spallanzani”, Rome, Italy

    Daniela Fioriti

  4. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA

    Valeria Pietropaolo

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  1. Anna Bellizzi
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  2. Elena Anzivino
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Correspondence to Valeria Pietropaolo.

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Bellizzi, A., Anzivino, E., Ferrari, F. et al. Polyomavirus JC reactivation and noncoding control region sequence analysis in pediatric Crohn's disease patients treated with infliximab. J. Neurovirol. 17, 303–313 (2011). https://doi.org/10.1007/s13365-011-0036-3

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  • DOI: https://doi.org/10.1007/s13365-011-0036-3

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