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Article

Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment

by
Carla Prezioso
1,2,*,
Marco Ciotti
3,
Gabriele Brazzini
2,
Francesca Piacentini
2,
Sara Passerini
2,
Alfonso Grimaldi
4,
Doriana Landi
4,5,
Carolina Gabri Nicoletti
4,5,
Maria Antonella Zingaropoli
2,
Marco Iannetta
5,
Marta Altieri
6,
Antonella Conte
6,7,
Dolores Limongi
8,
Girolama Alessandra Marfia
4,5,9,
Maria Rosa Ciardi
2,
Claudio Maria Mastroianni
2,
Anna Teresa Palamara
10,11,
Ugo Moens
12,† and
Valeria Pietropaolo
2,*,†
1
IRCSS San Raffaele Roma, Microbiology of Chronic Neuro-Degenerative Pathologies, 00163 Rome, Italy
2
Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy
3
Laboratory of Virology, Polyclinic Tor Vergata Foundation, 00133 Rome, Italy
4
Multiple Sclerosis Clinical and Research Unit, Fondazione Policlinico di Tor Vergata, 00133 Rome, Italy
5
Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
6
Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy
7
IRCCS Neuromed, 86077 Pozzilli, IS, Italy
8
IRCCS San Raffaele Roma, Telematic University, 00163 Rome, Italy
9
Unit of Neurology, IRCCS Istituto Neurologico Mediterraneo NEUROMED, 86077 Pozzilli, IS, Italy
10
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
11
Department of Public Health and Infectious Diseases, Laboratory Affiliated to Institute Pasteur Italia-Cenci Bolognetti Foundation, Sapienza University of Rome, 00185 Rome, Italy
12
Department of Medical Biology, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, 9037 Tromsø, Norway
*
Authors to whom correspondence should be addressed.
Equal senior-author contribution.
J. Clin. Med. 2022, 11(2), 347; https://doi.org/10.3390/jcm11020347
Submission received: 23 November 2021 / Revised: 7 January 2022 / Accepted: 10 January 2022 / Published: 11 January 2022
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Management, and Future Opportunities)

Abstract

Markers of JC polyomavirus (JCPyV) activity can be used to evaluate the risk of progressive multifocal leukoencephalopathy (PML) in treated multiple sclerosis (MS) patients. The presence of JCPyV DNA and microRNA (miR-J1-5p), the anti-JCV index and the sequence of the non-coding control region (NCCR) in urine and plasma were determined in 42 MS subjects before treatment (T0), 6 months (T6) and 12 months (T12) after natalizumab, ocrelizumab, fingolimod or dimethyl-fumarate administration and in 25 healthy controls (HC). The number of MS patients with viruria increased from 43% at T0 to 100% at T12, whereas it remained similar for the HC group (35–40%). Viremia first occurred 6 months after treatment in MS patients and increased after 12 months, whereas it was absent in HC. The viral load in urine and plasma from the MS cohort increased over time, mostly pronounced in natalizumab-treated patients, whereas it persisted in HC. The archetypal NCCR was detected in all positive urine, whereas mutations were observed in plasma-derived NCCRs resulting in a more neurotropic variant. The prevalence and miR-J1-5p copy number in MS urine and plasma dropped after treatment, whereas they remained similar in HC specimens. Viruria and miR-J1-5p expression did not correlate with anti-JCV index. In conclusion, analyzing JCPyV DNA and miR-J1-5p levels may allow monitoring JCPyV activity and predicting MS patients at risk of developing PML.
Keywords: progressive multifocal leukoencephalopathy; natalizumab; ocrelizumab; dimethyl-fumarate; fingolimod; JCPyV infection; non-coding control region progressive multifocal leukoencephalopathy; natalizumab; ocrelizumab; dimethyl-fumarate; fingolimod; JCPyV infection; non-coding control region

Share and Cite

MDPI and ACS Style

Prezioso, C.; Ciotti, M.; Brazzini, G.; Piacentini, F.; Passerini, S.; Grimaldi, A.; Landi, D.; Nicoletti, C.G.; Zingaropoli, M.A.; Iannetta, M.; et al. Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment. J. Clin. Med. 2022, 11, 347. https://doi.org/10.3390/jcm11020347

AMA Style

Prezioso C, Ciotti M, Brazzini G, Piacentini F, Passerini S, Grimaldi A, Landi D, Nicoletti CG, Zingaropoli MA, Iannetta M, et al. Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment. Journal of Clinical Medicine. 2022; 11(2):347. https://doi.org/10.3390/jcm11020347

Chicago/Turabian Style

Prezioso, Carla, Marco Ciotti, Gabriele Brazzini, Francesca Piacentini, Sara Passerini, Alfonso Grimaldi, Doriana Landi, Carolina Gabri Nicoletti, Maria Antonella Zingaropoli, Marco Iannetta, and et al. 2022. "Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment" Journal of Clinical Medicine 11, no. 2: 347. https://doi.org/10.3390/jcm11020347

APA Style

Prezioso, C., Ciotti, M., Brazzini, G., Piacentini, F., Passerini, S., Grimaldi, A., Landi, D., Nicoletti, C. G., Zingaropoli, M. A., Iannetta, M., Altieri, M., Conte, A., Limongi, D., Marfia, G. A., Ciardi, M. R., Mastroianni, C. M., Palamara, A. T., Moens, U., & Pietropaolo, V. (2022). Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment. Journal of Clinical Medicine, 11(2), 347. https://doi.org/10.3390/jcm11020347

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