JC virus (JCV) is the aetiological agent of a fatal demyelinating disease known as Progressive Multifocal Leukoencephalopathy (PML). The increased use of disease-modifying therapies (DMTs) for treatments of Multiple Sclerosis (MS), has expanded the patients at risk for developing PML. The metrics used to predict risk of PML could be implemented if, viral localization, viral genetic strain and host systemic immunity, were taken into account. In this regard it will be proposed to: evaluate JC viral load variations during DMTs; detect viral variants and specific genotypes circulating within the study cohorts; find out the effect of the treatments on the concentration of the circulating cytokines/chemokines and explore their role in establishing a balance between subpopulations of T helper cells. Improved approaches to PML risk stratification, are needed to guide treatment choices, surveillance of patients with MS and optimization of healthcare resources.
PML is a demyelinating disease of the CNS caused by JCV reactivation in a setting of cellular immunosuppression. Epidemiology, clinical presentation and prognosis of PML have been modified because of the use of selective DMTs medications for treatments of MS. The initial prevalence of Natalizumab-associated PML in patients with MS was estimated 1/1000. More than 750 PML cases have now been confirmed among Natalizumab-treated patients, with a fatality rate higher than 20% and substantial morbidity in survivors (6). The prevalence of PML in patients with MS who are taking other DMTs is lower than that associated with Natalizumab but is poorly studied. Therefore further investigations are crucial since JCV is widely diffused in healthy people and there is no known PML treatment. The detection of viruria may identify infected subjects when antibodies are still undetectable. Hence viruria and viremia follow up, in association with the detection of pathogenic NCCR, may provide a better PML stratification risk. Finally, the assessment of the MS-specific cytokine-chemokine pattern, could enrich scientific literature about the correlation between MS typical altered inflammation pattern and JCV load. To date, only opposite results are available. Therefore, it is crucial to clearly understand the risk of PML associated with DMTs to better inform risk/benefit decision-making. Our project could be noteworthy to identify biomarkers of early JCV associated pathology since it is difficult to discriminate the symptoms of a typical neurological MS dysfunction respect to the clinical suspicion of PML.