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Increased frequency of JC-polyomavirus detection in rheumatoid arthritis patients treated with multiple biologics
Jens Verheyen1, Kseniya Maizus, Eugen Feist
1Institute of Virology, National Reference Center for Papilloma- and Polyomaviruses, University of Cologne, Cologne, Germany, jens.verheyen@uk-essen.de.
Abstract:
Progressive multifocal leukoencephalopathy (PML) represents a rare but potentially fatal reactivation of JC-polyomavirus (JCPyV) recently also reported in patients with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA) treated with rituximab. The aim of the present study was to analyse the pattern of JCPyV infections in patients with RA undergoing treatment with biologic agents. Urine and blood samples were analysed from 80 patients for antibody levels and/or the presence of JCPyV DNA. Genotyping of the control region and VP1 was performed for all JCPyV DNA-positive specimens. Viremia of JCPyV was only temporarily detected in two patients, and these viruses did not carry any mutations associated with the occurrence of PML. JCPyV DNA was prevalent in initial urine samples of 33% of all patients. RA patients who have consecutively been treated with two or more biologic agents revealed significantly higher prevalence of JCPyV DNA in the urine compared to RA patients treated with their first biologic agent. The presence of JCPyV DNA in the urine closely correlated to JCPyV antibody positivity, and therefore, antibody titres were higher in RA patients who had consecutively received two or more biologic agents over time. Therefore, the overall number of biologic agents had an impact on the pattern of JCPyV detection in this study. Hence, JCPyV antibody screening might be useful as part of the PML risk stratification for RA patients in the future.
Insights
JC-polyomavirus (JCPyV) reactivation is a risk in rheumatoid arthritis (RA) patients treated with biologics. Higher JCPyV DNA prevalence in urine correlates with multiple biologic treatments, suggesting JCPyV antibody screening for PML risk stratification.
Area of Science:
- Immunology
- Virology
- Rheumatology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, fatal JC-polyomavirus (JCPyV) reactivation.
- PML has been observed in autoimmune disease patients, including rheumatoid arthritis (RA), treated with rituximab.
- Biologic agents are increasingly used for RA, necessitating an understanding of associated viral risks.
Purpose of the Study:
- To investigate the prevalence and patterns of JCPyV infection in RA patients undergoing biologic therapy.
- To determine if the number or type of biologic agents influences JCPyV detection.
- To assess the potential of JCPyV antibody screening for PML risk stratification in RA patients.
Main Methods:
- Analysis of urine and blood samples from 80 RA patients for JCPyV DNA and antibody levels.
- Genotyping of JCPyV control region and VP1 in positive specimens.
- Correlation analysis between JCPyV detection, antibody titers, and patient treatment history (number of biologic agents).
Main Results:
- JCPyV DNA was detected in the urine of 33% of RA patients.
- Viremia was transient and detected in only two patients, without PML-associated mutations.
- Significantly higher JCPyV DNA prevalence and antibody titers were observed in patients treated with two or more biologic agents compared to those on their first biologic.
- JCPyV DNA detection in urine strongly correlated with JCPyV antibody positivity.
Conclusions:
- The number of biologic agents used in RA treatment impacts JCPyV detection patterns.
- JCPyV infection prevalence and antibody response increase with cumulative exposure to biologic therapies.
- JCPyV antibody screening may be a valuable tool for PML risk stratification in RA patients undergoing biologic treatment.
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