Progressive multifocal leukoencephalopathy (PML) onset, caused by Polyomavirus JC (JCPyV) in patients affected by multiple sclerosis (MS) during natalizumab treatment, raised concerns about the safety profile of this agent. Therefore, the aims of this study were the JCPyV reactivation monitoring and the noncoding control region (NCCR) and viral protein 1 (VP1) analysis in patients affected by MS and treated with natalizumab.We performed JCPyV-specific quantitative PCR of biological samples collected at moment of recruitment (t0) and every 4 months (t1, t2, t3) for 1 year. Subsequently, rearrangements’ analysis of NCCR and VP1 was carried out. Moreover a 2-step virus-like particle-based enzyme-linked immunosorbed assay was performed at t0 and t3, to detect specific anti-JC virus antibodies in serum of the enrolled subjects. Data were analyzed using chi-square test.Results showed a significant association between JC viruria and JCPyV antibodies after 1 year of natalizumab (p=0.04). Moreover, sequences isolated from peripheral blood mononuclear cells (PBMCs) of 2 patients with JCPyV antibody at t0 and t3, showed a NCCR Type IIR with a duplication of a 98bp unit and a 66bp insert, resulting in a boxB deletion and 37 T to G transversion into the Spi-B binding site. In all patients, a prevalence of genotypes 1A and 1B, the predominant JCPyV genotypes in Europe, was observed.In conclusion, it could be important to understand whether the specific inflammatory scenario of multiple sclerosis could affect JCPyV reactivation from latency, in particular from kidneys. Moreover, for a more accurate PML risk stratification, testing JC viruria seems to be useful to identify patients who harbor JCPyV but with an undetectable JCPyV-specific humoral immune response. In these patients, it may also be important to study the JCPyV NCCR rearrangement: in particular, Spi-B expression in PBMCs could play a crucial role in JCPyV replication and NCCR rearrangement.
Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic cohorts of individuals affected by multiple sclerosis under treatment with natalizumab: an observational study / Bellizzi, Anna; Anzivino, Elena; Rodio, DONATELLA MARIA; S., Cioccolo; Morreale, Manuela; Pontecorvo, Simona; S., Carluccio; Nencioni, Lucia; Francia, Ada; Palamara, ANNA TERESA; Pietropaolo, Valeria Antonietta. - In: JOURNAL OF NEUROVIROLOGY. - ISSN 1355-0284. - ELETTRONICO. - 19:1(2013), pp. S12-S12. (Intervento presentato al convegno 12th International Symposium on NeuroVirology tenutosi a Washington, DC nel OCT 29-NOV 02, 2013).
Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic cohorts of individuals affected by multiple sclerosis under treatment with natalizumab: an observational study
BELLIZZI, ANNA;ANZIVINO, ELENA;RODIO, DONATELLA MARIA;MORREALE, MANUELA;PONTECORVO, SIMONA;NENCIONI, Lucia;FRANCIA, Ada;PALAMARA, ANNA TERESA;PIETROPAOLO, Valeria Antonietta
2013
Abstract
Progressive multifocal leukoencephalopathy (PML) onset, caused by Polyomavirus JC (JCPyV) in patients affected by multiple sclerosis (MS) during natalizumab treatment, raised concerns about the safety profile of this agent. Therefore, the aims of this study were the JCPyV reactivation monitoring and the noncoding control region (NCCR) and viral protein 1 (VP1) analysis in patients affected by MS and treated with natalizumab.We performed JCPyV-specific quantitative PCR of biological samples collected at moment of recruitment (t0) and every 4 months (t1, t2, t3) for 1 year. Subsequently, rearrangements’ analysis of NCCR and VP1 was carried out. Moreover a 2-step virus-like particle-based enzyme-linked immunosorbed assay was performed at t0 and t3, to detect specific anti-JC virus antibodies in serum of the enrolled subjects. Data were analyzed using chi-square test.Results showed a significant association between JC viruria and JCPyV antibodies after 1 year of natalizumab (p=0.04). Moreover, sequences isolated from peripheral blood mononuclear cells (PBMCs) of 2 patients with JCPyV antibody at t0 and t3, showed a NCCR Type IIR with a duplication of a 98bp unit and a 66bp insert, resulting in a boxB deletion and 37 T to G transversion into the Spi-B binding site. In all patients, a prevalence of genotypes 1A and 1B, the predominant JCPyV genotypes in Europe, was observed.In conclusion, it could be important to understand whether the specific inflammatory scenario of multiple sclerosis could affect JCPyV reactivation from latency, in particular from kidneys. Moreover, for a more accurate PML risk stratification, testing JC viruria seems to be useful to identify patients who harbor JCPyV but with an undetectable JCPyV-specific humoral immune response. In these patients, it may also be important to study the JCPyV NCCR rearrangement: in particular, Spi-B expression in PBMCs could play a crucial role in JCPyV replication and NCCR rearrangement.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
