Increased frequency of JC-polyomavirus detection in rheumatoid arthritis patients treated with multiple biologics

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.

Increased Prevalence of Human Polyomavirus JC Viruria in Chronic Inflammatory Rheumatic Diseases Patients in Treatment with Anti-TNF α: A 18 Month Follow-Up Study

“…In JCPyV DNA positive patients, NCCR sequencing always revealed the presence of archetype-like structures, according to other Authors (Giannecchini et al, 2012 ; Verheyen et al, 2015 ), except for a rearranged NCCR form detected in the plasma sample of a patient affected by PsA (Figure 3B ). Interestingly, this type II-R rearrangement resembles the viral variants isolated in subjects who developed PML, and it is characterized by a marked neurotropism (Agostini et al, 2001 ; Marzocchetti et al, 2007 ).…”

“…Regarding viremia, it was mainly associated to viruria during the entire follow-up (Figure 1 ). Although JC viremia seems to be essential for the development of PML and it was detected in 37.5% (12/32) of our patients at T18, its short temporality precludes its usefulness in screening or diagnostic algorithms, as already demonstrated by other Authors in comparable studies (Rinaldi et al, 2010 ; Bellizzi et al, 2015 ; Verheyen et al, 2015 ). Hence, monitoring urine JCPyV replication is a good, non-invasive method to check viral pathogenic potential.…”

“…In fact, over the time, no difference was observed between JCPyV-positive and JCPyV-negative patients treated with single administration of biologics or co-administration of DMARDs and/or GC (Table 5 ). Conversely, a previous study demonstrated a positive correlation between the JCPyV DNA detection in the urine and the number of biologics consecutively used for RA treatment (Verheyen et al, 2015 ). However, it is possible to hypothesize that the prolonged administration of biologic agents over time had a causative role in the increasing number of patients with JC viruria after 18 months of anti-TNF-α treatment.…”

Neuropsychiatric manifestations in rheumatoid arthritis

“…Many different agents were described in patients with RA, with especial attention for tuberculosis, neurolues, fungal and viral infections [44][45][46][47][48]. Patients taking TNF-α inhibitors and others biologic agents (such as infliximab, adalimumab, golimumab, etanercept and certolizumab) are at great risk for serious infections events such as tuberculosis and infections caused by opportunistic agents (histoplasmosis, coccidiodomycosis and Pneumocystis pneumonia are the most frequent agents) [49].…”