Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding

Abstract

Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or β-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.

HPyV6 and HPyV7 in urine from immunocompromised patients

“…CSF from 10 MS patients were negative for HPyV6 and HPyV7 DNA [42], suggesting that reactivation of these two HPyVs may be a rare event in MS patients. Studies by several groups have shown that BKPyV, JCPyV or both can be detected in urine from MS patients receiving natalizumab or β-interferon [76][77][78][79][80][81], indicating that HPyV viruria is not uncommon in these patients.…”

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

“… 267 Analysis of serum‐derived EV microRNAs also demonstrated that a variety of microRNAs were associated with MS recurrence and activity, 264 , 268 , 269 and can be used to support personalized treatment decisions. Exosomes are also used in the diagnosis and monitoring of immune disorders such as multifocal leukoencephalopathy (PML), 270 Sjögren's syndrome, 271 autoimmune skin diseases, 272 IgA neuropathies, 273 adult myasthenia gravis, 274 and inflammatory bowel disease. 275 , 276 …”

Extracellular Vesicles in Multiple Sclerosis: Role in the Pathogenesis and Potential Usefulness as Biomarkers and Therapeutic Tools

“…Indeed, Giovannelli and collaborators detected, for the first time, both JCPyV miRNAs not only in blood cells but also in urinary and plasmatic EVs of patients at risk of progressive multifocal leukoencephalopathy (PML) versus HC. The reactivation of JCPyV, causing PML, represents a concrete risk of MS patients under natalizumab treatment [ 81 ]. Therefore, this finding could conceal a repression mechanism of viral replication during the asymptomatic phase of JCPyV.…”