JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients

Area of Science:

• Virology
• Immunology
• Neurology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a risk for natalizumab-treated multiple sclerosis (MS) patients due to JC virus (JCV) reactivation.
• Current recommendations suggest excluding JCV-seropositive patients from natalizumab treatment, assuming seropositivity indicates infection.
• 430 cases of PML have been reported in natalizumab-treated MS patients.

Purpose of the Study:

• To investigate the presence and dynamics of JCV and BK virus (BKV) DNA in urine and blood of natalizumab-treated MS patients.
• To evaluate the correlation between JCV seropositivity and viral shedding.
• To assess the adequacy of serological tests in identifying JCV carriers.

Main Methods:

• Monthly urine and blood samples were collected from 42 natalizumab-treated MS patients for up to 60 months.
• Quantitative real-time PCR assays were used to detect JCV and BKV DNA.
• Serum anti-JCV antibodies were measured using Stratify and/or Stratify DxSelect tests.

Main Results:

• JCV and BKV DNA were undetectable in blood but present in urine in 50% and 59.5% of patients, respectively.
• JCV urinary shedding increased up to 24 months of treatment, with a significant time effect (p=0.04).
• Three JCV-seronegative patients exhibited JCV DNA in urine, indicating a lack of complete correlation between serology and shedding.

Conclusions:

• Natalizumab therapy may increase the rate of JCV urinary shedding in MS patients.
• Serological tests alone are insufficient for accurately identifying JCV-uninfected individuals.
• Sensitive viral DNA detection methods are crucial for precise identification of JCV carriers.