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JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?

Verbeeck, J.; Van Assche, G.; Ryding, Janka LU ; Wollants, E.; Rans, K.; Vermeire, S.; Pourkarim, M. R.; Noman, M.; Dillner, Joakim LU and Van Ranst, M., et al. (2008) In Gut 57(10). p.1393-1397
Abstract
Background and aims: Anti-alpha 4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease 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-alpha 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 patients with Crohn's disease, 100 control subjects with gastrointestinal (GI) disease, and 106 healthy volunteers. Four to eight weeks after this first sample collection, we additionally collected a set of urine, serum, plasma and buffy coat... (More)
Background and aims: Anti-alpha 4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease 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-alpha 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 patients with Crohn's disease, 100 control subjects with gastrointestinal (GI) disease, and 106 healthy volunteers. Four to eight weeks after this first sample collection, we additionally collected a set of urine, serum, plasma and buffy coat samples from the 125 patients with Crohn's disease, and a next set of samples was collected 12-16 weeks after the first collection. JC viral loads were determined with quantitative real-time polymerase chain reaction (PCR), and JC virus seroprevalence with a specific enzyme-linked immunosorbant assay ( ELISA). Results: The overall JC virus seroprevalence was 65%. JC virus DNA copies were detected in the urine from 29-44% of subjects, both those with Crohn's disease and controls. Median viral loads were significantly higher in patients with Crohn's disease who were immunosuppressed (7.36x10(6) copies/ml) compared to healthy volunteers (2.77x10(5) copies/ml) and compared to GI controls (1.8x10(6) copies/ml). Clearance at any time point occurred in 4/107 (3.7%) subjects only. JC viraemia was found in two patients with Crohn's disease. Conclusions: The natural history of JC virus in patients with Crohn's disease is still unknown. Our study results show that JC virus latency and urine viral shedding is frequent in immunosuppressed patients with Crohn's disease. More prospective studies are needed in order to agree on possible recommendations concerning the exclusion of patients with JCV viraemia from anti-alpha 4 integrin treatment. (Less)
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Contribution to journal
publication status
published
subject
in
Gut
volume
57
issue
10
pages
1393 - 1397
publisher
BMJ Publishing Group
external identifiers
  • wos:000259198800015
  • scopus:52649134405
ISSN
1468-3288
DOI
10.1136/gut.2007.145698
language
English
LU publication?
yes
id
04dd1fb8-91a5-4e91-a73b-cf8e4e159e1f (old id 1246961)
date added to LUP
2008-11-17 10:58:38
date last changed
2017-08-20 03:52:50
@article{04dd1fb8-91a5-4e91-a73b-cf8e4e159e1f,
  abstract     = {Background and aims: Anti-alpha 4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease 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-alpha 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 patients with Crohn's disease, 100 control subjects with gastrointestinal (GI) disease, and 106 healthy volunteers. Four to eight weeks after this first sample collection, we additionally collected a set of urine, serum, plasma and buffy coat samples from the 125 patients with Crohn's disease, and a next set of samples was collected 12-16 weeks after the first collection. JC viral loads were determined with quantitative real-time polymerase chain reaction (PCR), and JC virus seroprevalence with a specific enzyme-linked immunosorbant assay ( ELISA). Results: The overall JC virus seroprevalence was 65%. JC virus DNA copies were detected in the urine from 29-44% of subjects, both those with Crohn's disease and controls. Median viral loads were significantly higher in patients with Crohn's disease who were immunosuppressed (7.36x10(6) copies/ml) compared to healthy volunteers (2.77x10(5) copies/ml) and compared to GI controls (1.8x10(6) copies/ml). Clearance at any time point occurred in 4/107 (3.7%) subjects only. JC viraemia was found in two patients with Crohn's disease. Conclusions: The natural history of JC virus in patients with Crohn's disease is still unknown. Our study results show that JC virus latency and urine viral shedding is frequent in immunosuppressed patients with Crohn's disease. More prospective studies are needed in order to agree on possible recommendations concerning the exclusion of patients with JCV viraemia from anti-alpha 4 integrin treatment.},
  author       = {Verbeeck, J. and Van Assche, G. and Ryding, Janka and Wollants, E. and Rans, K. and Vermeire, S. and Pourkarim, M. R. and Noman, M. and Dillner, Joakim and Van Ranst, M. and Rutgeerts, P.},
  issn         = {1468-3288},
  language     = {eng},
  number       = {10},
  pages        = {1393--1397},
  publisher    = {BMJ Publishing Group},
  series       = {Gut},
  title        = {JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?},
  url          = {http://dx.doi.org/10.1136/gut.2007.145698},
  volume       = {57},
  year         = {2008},
}