JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients

Basnyat, Pabitra; Virtanen, Elina; Elovaara, Irina; Hagman, Sanna; Auvinen, Eeva

doi:10.1007/s13365-017-0560-x

Cited by 10 publications

(5 citation statements)

References 38 publications

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“…However, it is important to underline that in this case miRNAs extraction was performed from exosomes and not directly from urine. The presence of circulatory JCPyV miRNAs in JCPyV-seronegative MS patients was also confirmed in a recent work on patients treated with Natalizumab and interferon-beta, in whom miR-J1-5p was measured directly from plasma [53]. In that cross-sectional work miR-J1-5p was detected in 78% of JCPyV seronegative MS patients-and in 84% of patients treated with Natalizumab.…”

Section: Discussionsupporting

confidence: 53%

JCPyV miR-J1-5p in Urine of Natalizumab-Treated Multiple Sclerosis Patients

Agostini

Mancuso

Costa

et al. 2021

Viruses

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The use of Natalizumab in Multiple Sclerosis (MS) can cause the reactivation of the polyomavirus JC (JCPyV); this may result in the development of progressive multifocal leukoencephalopathy (PML), a rare and usually lethal disease. JCPyV infection is highly prevalent in worldwide population, but the detection of anti-JCPyV antibodies is not sufficient to identify JCPyV infection, as PML can develop even in patients with negative JCPyV serology. Better comprehension of the JCPyV biology could allow a better understanding of JCPyV infection and reactivation, possibly reducing the risk of developing PML. Here, we investigated whether JCPyV miR-J1-5p—a miRNA that down-regulates the early phase viral protein T-antigen and promotes viral latency—could be detected and quantified by digital droplet PCR (ddPCR) in urine of 25 Natalizumab-treated MS patients. A 24-month study was designed: baseline, before the first dose of Natalizumab, and after 1 (T1), 12 (T12) and 24 months (T24) of therapy. miR-J1-5p was detected in urine of 7/25 MS patients (28%); detection was possible in three cases at T24, in two cases at T12, in one case at T1 and T12, and in the last case at baseline and T1. Two of these patients were seronegative for JCPyV Ab, and viral DNA was never found in either urine or blood. To note, only in one case miR-J1-5p was detected before initiation of Natalizumab. These results suggest that the measurement of miR-J1-5p in urine, could be a biomarker to monitor JCPyV infection and to better identify the possible risk of developing PML in Natalizumab-treated MS patients.

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Section: Discussionsupporting

confidence: 53%

JCPyV miR-J1-5p in Urine of Natalizumab-Treated Multiple Sclerosis Patients

Agostini

Mancuso

Costa

et al. 2021

Viruses

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“…The miR-J1-5p copy number reduced by almost 50% in both urine and serum at T12. Thus, treatment may stimulate viral replication by reducing miR-J1-5p, which downregulates expression of large T-antigen, a protein absolutely required for viral replication [31]. The concomitant analysis between shedders and non-shedders and miR-J1-5p evidenced that miR-J1-5p expression was inversely correlated with JCPyV detection.…”

Section: Discussionmentioning

confidence: 98%

“…The pri-miR-J1 is processed into a precursor miRNA (pre-miR-J1) that produces two mature miRNAs: miR-J1-5p and -3p [29]. The discovery of JCPyV miRNAs circulating in biofluids encouraged their use as diagnostic markers [31]. Indeed, JCPyV-encoded miRNAs have been identified in PML tissues [29], in multiple sclerosis patients undergoing natalizumab treatment [32], in HIV-infected patients [33], in cancer patients [34] and in healthy people [35].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment

Prezioso

Sagnelli

Brazzini

et al. 2022

JCM

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Markers of JC polyomavirus (JCPyV) activity can be used to evaluate the risk of progressive multifocal leukoencephalopathy (PML) in treated multiple sclerosis (MS) patients. The presence of JCPyV DNA and microRNA (miR-J1-5p), the anti-JCV index and the sequence of the non-coding control region (NCCR) in urine and plasma were determined in 42 MS subjects before treatment (T0), 6 months (T6) and 12 months (T12) after natalizumab, ocrelizumab, fingolimod or dimethyl-fumarate administration and in 25 healthy controls (HC). The number of MS patients with viruria increased from 43% at T0 to 100% at T12, whereas it remained similar for the HC group (35–40%). Viremia first occurred 6 months after treatment in MS patients and increased after 12 months, whereas it was absent in HC. The viral load in urine and plasma from the MS cohort increased over time, mostly pronounced in natalizumab-treated patients, whereas it persisted in HC. The archetypal NCCR was detected in all positive urine, whereas mutations were observed in plasma-derived NCCRs resulting in a more neurotropic variant. The prevalence and miR-J1-5p copy number in MS urine and plasma dropped after treatment, whereas they remained similar in HC specimens. Viruria and miR-J1-5p expression did not correlate with anti-JCV index. In conclusion, analyzing JCPyV DNA and miR-J1-5p levels may allow monitoring JCPyV activity and predicting MS patients at risk of developing PML.

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“…Natalizumab, dimethyl fumarate, fingolimod, alemtuzumab, and ocrelizumab have all been associated with cases of progressive multifocal leukoencephalopathy (PML) caused by JC polyomavirus (JCPyV). The measurement of plasma indexes of anti-JCPyV antibodies helps stratify patients treated with natalizumab who are at risk of PML [72], and this index is used as a clinical indicator that natalizumab needs to be changed or withdrawn. JCPyV infects the endothelial cells of the choroid plexus by attachment through specific receptors and infiltrates the brain parenchyma, infecting oligodendrocytes and astrocytes.…”

Section: Evs As Biomarkers Of Adverse Events After Dmtsmentioning

confidence: 99%

Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis

Gutiérrez-Fernández

Cuesta

Tallón

et al. 2021

IJMS

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Extracellular vesicles (EVs) are a heterogeneous group of bilayer membrane-wrapped molecules that play an important role in cell-to-cell communication, participating in many physiological processes and in the pathogenesis of several diseases, including multiple sclerosis (MS). In recent years, many studies have focused on EVs, with promising results indicating their potential role as biomarkers in MS and helping us better understand the pathogenesis of the disease. Recent evidence suggests that there are novel subpopulations of EVs according to cell origin, with those derived from cells belonging to the nervous and immune systems providing information regarding inflammation, demyelination, axonal damage, astrocyte and microglia reaction, blood–brain barrier permeability, leukocyte transendothelial migration, and ultimately synaptic loss and neuronal death in MS. These biomarkers can also provide insight into disease activity and progression and can differentiate patients’ disease phenotype. This information can enable new pathways for therapeutic target discovery, and consequently the development of novel treatments. Recent evidence also suggests that current disease modifying treatments (DMTs) for MS modify the levels and content of circulating EVs. EVs might also serve as biomarkers to help monitor the response to DMTs, which could improve medical decisions concerning DMT initiation, choice, escalation, and withdrawal. Furthermore, EVs could act not only as biomarkers but also as treatment for brain repair and immunomodulation in MS. EVs are considered excellent delivery vehicles. Studies in progress show that EVs containing myelin antigens could play a pivotal role in inducing antigen-specific tolerance of autoreactive T cells as a novel strategy for the treatment as “EV-based vaccines” for MS. This review explores the breakthrough role of nervous and immune system cell-derived EVs as markers of pathological disease mechanisms and potential biomarkers of treatment response in MS. In addition, this review explores the novel role of EVs as vehicles for antigen delivery as a therapeutic vaccine to restore immune tolerance in MS autoimmunity.

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JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients

Cited by 10 publications

References 38 publications

JCPyV miR-J1-5p in Urine of Natalizumab-Treated Multiple Sclerosis Patients

JCPyV miR-J1-5p in Urine of Natalizumab-Treated Multiple Sclerosis Patients

Diagnostic Value of JC Polyomavirus Viruria, Viremia, Serostatus and microRNA Expression in Multiple Sclerosis Patients Undergoing Immunosuppressive Treatment

Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis

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