JC viral loads in crohn's disease patients treated with immunosuppression: can we screen for elevated risk of PML?

¹ Laboratory of Clinical Virology, Rega Institute for Medical Research, Leuven, Belgium
² Division of Gastroenterology, Leuven University Hospital, Leuven, Belgium
³ Department of Medical Microbiology, Lund University, Malmö, Sweden

^* To whom correspondence should be addressed. E-mail: gert.vanassche{at}uz.kuleuven.ac.be.

Accepted 15 April 2008

	Abstract

Background and aims Anti-4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease (CD) and in multiple sclerosis, but carries an estimated 1/1000 risk of progressive multifocal leukoencephalopathy (PML) caused by reactivation of latent JC virus infection. Athough anti-4 integrin therapies are likely to be introduced in the clinic, screening for the risk of PML has not been developed.

Methods We prospectively collected urine, serum, plasma and buffy coats from 125 CD patients, 100 gastrointestinal disease controls (GI), and 106 healthy volunteers (HV). 4-8 weeks after this first sample collection, we additionally collected a set of urine, serum, plasma and buffy coat samples from the 125 CD patients, and a next set of samples was collected 12-16 weeks after the first collection. JC viral loads were determined with quantitative real time PCR, and JC virus seroprevalence with specific ELISA.

Results The overall JC virus seroprevalence was 65%. JC virus DNA copies were detected in the urine of 29-44% of subjects, both CD and controls. Median viral loads were significantly higher in immunosuppressed CD patients (7.36 x 10⁶ copies/mL) compared to HV (2.77 x 10⁵ copies/mL) and compared to GI controls (1.8 x 10⁶ copies/mL). Clearance at any time point occurred in 4/107 (3.7%) subjects only. JC viremia was found in 2 CD patients.

Conclusions The natural history of JC virus in CD patients is still unknown. Our study results show that JC virus latency and urine viral shedding is frequent in immunosuppressed CD patients. More prospective studies are needed in order to agree on possible recommendations concerning the exclusion of patients with JCV viremia from anti-4 integrin therapy.