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

Area of Science:

• Virology
• Neuroimmunology
• Molecular Diagnostics

Background:

• Natalizumab treatment for Multiple Sclerosis (MS) carries a risk of John Cunningham polyomavirus (JCPyV) reactivation, potentially causing fatal progressive multifocal leukoencephalopathy (PML).
• Current JCPyV detection methods, like antibody testing, are insufficient for predicting PML risk, as the disease can occur even in seronegative individuals.
• Understanding JCPyV biology and developing new detection strategies are crucial for mitigating PML risk in MS patients.

Purpose of the Study:

• To investigate the detectability and quantification of JCPyV miR-J1-5p, a microRNA involved in JCPyV latency, in the urine of Natalizumab-treated MS patients.
• To assess the potential of urinary miR-J1-5p as a biomarker for monitoring JCPyV infection and predicting PML risk.

Main Methods:

• A longitudinal study involving 25 Natalizumab-treated MS patients over 24 months.
• Urine samples were collected at baseline and at 1, 12, and 24 months post-treatment initiation.
• Digital droplet PCR (ddPCR) was employed to detect and quantify JCPyV miR-J1-5p in urine samples.

Main Results:

• JCPyV miR-J1-5p was detected in the urine of 7 out of 25 (28%) MS patients.
• Detection occurred at various time points, including baseline and up to 24 months of therapy.
• Notably, miR-J1-5p was detected in two JCPyV antibody-seronegative patients, and viral DNA was absent in their urine and blood, suggesting a potential for detecting infection independent of serology.

Conclusions:

• Urinary JCPyV miR-J1-5p can be detected in a subset of Natalizumab-treated MS patients.
• This microRNA shows promise as a non-invasive biomarker for monitoring JCPyV infection.
• Measurement of miR-J1-5p may aid in identifying MS patients at higher risk for developing PML during Natalizumab therapy.