Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic cohorts of individuals affected by immune-mediated diseases under treatment with biologics: an observational study

Virology Journal

Valeria Pietropaolo⁶  Anna Teresa Palamara⁴  Salvatore Cucchiara²  Ada Francia⁷  Guido Valesini⁵  Silvia Carluccio⁸  Lucia Nencioni¹  Giovanni Di Nardo²  Federica Ferrari²  Simona Pontecorvo⁷  Manuela Morreale³  Rossana Scrivo⁵  Sara Cioccolo⁹  Donatella Maria Rodio⁹  Elena Anzivino⁹  Anna Bellizzi⁹ 

[1] Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci-Bolognetti Foundation, Sapienza University of Rome, Rome, Italy;Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy;Department of Medico-Surgical Sciences and Biotechnologies, Section of Neurology, Sapienza University of Rome, Rome, Italy;San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, Rome, Italy;Department of Internal Medicine and Medical Disciplines, Rheumatology, Sapienza University of Rome, Rome, Italy;Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA;Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy;Department of Biomedical, Surgery and Dental Sciences, University of Milan, via Pascal 36, 20123 Milan, Italy;Department of Public Health and Infectious Diseases, Sapienza University, P.le Aldo Moro, 5, 00185 Rome, Italy

关键词: VP1;    NCCR;    anti-TNF;    Crohn’s disease;    Chronic inflammatory rheumatic diseases;    Natalizumab;    Multiple sclerosis;    JCPyV-specific antibodies;    q-PCR;    JCPyV;   

Others  :  821256
DOI  :  10.1186/1743-422X-10-298

 received in 2013-07-04, accepted in 2013-09-27,  发布年份 2013

【 摘 要 】

Background

Progressive multifocal leukoencephalopathy (PML) onset, caused by Polyomavirus JC (JCPyV) in patients affected by immune-mediated diseases during biological treatment, raised concerns about the safety profile of these agents. 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 different immune-mediated diseases and treated with biologics.

Methods

We performed JCPyV-specific quantitative PCR of biological samples collected at moment of recruitment (t0) and every 4 months (t1, t2, t3, t4). Subsequently, rearrangements’ analysis of NCCR and VP1 was carried out. Data were analyzed using χ² test.

Results

Results showed that at t0 patients with chronic inflammatory rheumatic diseases presented a JCPyV load in the urine significantly higher (p≤0.05) than in patients with multiple sclerosis (MS) and Crohn’s disease (CD). It can also be observed a significant association between JC viruria and JCPyV antibodies after 1 year of natalizumab (p=0.04) in MS patients. Finally, NCCR analysis showed the presence of an archetype-like sequence in all urine samples, whereas a rearranged NCCR Type IR was found in colon-rectal biopsies collected from 2 CD patients after 16 months of infliximab. Furthermore, sequences isolated from peripheral blood mononuclear cells (PBMCs) of 2 MS patients with JCPyV antibody at t0 and t3, showed a NCCR Type IIR with a duplication of a 98 bp unit and a 66 bp 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.

Conclusions

It has been important to understand whether the specific inflammatory scenario in different immune-mediated diseases 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.

【 授权许可】

   
2013 Bellizzi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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