The occurrence of progressive multifocal leukoencephalopathy (PML) caused by Polyomavirus JC (JCV) in patients affected by multiple sclerosis (MS) treated with natalizumab has raised concerns about the safety of this drug. In this study, we performed a JCV-specific quantitative PCR on biological samples collected at the enrollment (t0) and every 4 months (t1, t2, t3) for 1 year and in the second year of treatment (t4, t5). Then, specific PCR products for JCV NCCR and VP1 sequences were analyzed. Moreover, JCV-specific antibodies were assessed by STRATIFY JCV® in serum at t0 and t3. After 1 year of natalizumab treatment, results showed a significant association between patients with JC viruria and positive STRATIFY JCV® with respect to those patients with no JCV-specific antibodies (p=0.0006). Moreover, at t4 the JC viremia was prevalently observed rather than JC viruria (p=0.04). Regarding NCCR sequence analysis, in peripheral blood mononuclear cells of patients STRATIFY JCV® positive at t3 and treated with 12 natalizumab infusions, NCCR sequencing revealed the presence of rearranged sequences. Finally, VP1 sequence analysis showed the prevalence of the genotypes 1A, 1B and 4. In conclusion, testing JC viruria seems to be useful to identify patients who harbor JCV with an undetectable specific humoral immune response. It may also be important to study the JCV NCCR rearrangements since they could generate neuro-invasive viral variants increasing the risk of PML onset.

Human polyomavirus JC replication and non coding control region analysis in multiple sclerosis patients under natalizumab treatment / Pietropaolo, Valeria Antonietta; Bellizzi, Anna; Anzivino, Elena; Iannetta, Marco; Zingaropoli, MARIA ANTONELLA; Rodio, DONATELLA MARIA; Morreale, Manuela; Pontecorvo, Simona; Francia, Ada; Vullo, Vincenzo; Palamara, ANNA TERESA; Ciardi, Maria Rosa. - In: JOURNAL OF NEUROVIROLOGY. - ISSN 1355-0284. - ELETTRONICO. - 21:6(2015), pp. 653-665. [10.1007/s13365-015-0338-y]

Human polyomavirus JC replication and non coding control region analysis in multiple sclerosis patients under natalizumab treatment

PIETROPAOLO, Valeria Antonietta;BELLIZZI, ANNA;ANZIVINO, ELENA;IANNETTA, MARCO;ZINGAROPOLI, MARIA ANTONELLA;RODIO, DONATELLA MARIA;MORREALE, MANUELA;PONTECORVO, SIMONA;FRANCIA, Ada;VULLO, Vincenzo;PALAMARA, ANNA TERESA;CIARDI, Maria Rosa
2015

Abstract

The occurrence of progressive multifocal leukoencephalopathy (PML) caused by Polyomavirus JC (JCV) in patients affected by multiple sclerosis (MS) treated with natalizumab has raised concerns about the safety of this drug. In this study, we performed a JCV-specific quantitative PCR on biological samples collected at the enrollment (t0) and every 4 months (t1, t2, t3) for 1 year and in the second year of treatment (t4, t5). Then, specific PCR products for JCV NCCR and VP1 sequences were analyzed. Moreover, JCV-specific antibodies were assessed by STRATIFY JCV® in serum at t0 and t3. After 1 year of natalizumab treatment, results showed a significant association between patients with JC viruria and positive STRATIFY JCV® with respect to those patients with no JCV-specific antibodies (p=0.0006). Moreover, at t4 the JC viremia was prevalently observed rather than JC viruria (p=0.04). Regarding NCCR sequence analysis, in peripheral blood mononuclear cells of patients STRATIFY JCV® positive at t3 and treated with 12 natalizumab infusions, NCCR sequencing revealed the presence of rearranged sequences. Finally, VP1 sequence analysis showed the prevalence of the genotypes 1A, 1B and 4. In conclusion, testing JC viruria seems to be useful to identify patients who harbor JCV with an undetectable specific humoral immune response. It may also be important to study the JCV NCCR rearrangements since they could generate neuro-invasive viral variants increasing the risk of PML onset.
2015
polyomavirus jc; multiple sclerosis; natalizumab; stratify jcv®; real time pcr; nccr sequencing
01 Pubblicazione su rivista::01a Articolo in rivista
Human polyomavirus JC replication and non coding control region analysis in multiple sclerosis patients under natalizumab treatment / Pietropaolo, Valeria Antonietta; Bellizzi, Anna; Anzivino, Elena; Iannetta, Marco; Zingaropoli, MARIA ANTONELLA; Rodio, DONATELLA MARIA; Morreale, Manuela; Pontecorvo, Simona; Francia, Ada; Vullo, Vincenzo; Palamara, ANNA TERESA; Ciardi, Maria Rosa. - In: JOURNAL OF NEUROVIROLOGY. - ISSN 1355-0284. - ELETTRONICO. - 21:6(2015), pp. 653-665. [10.1007/s13365-015-0338-y]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/781576
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