Journal article
Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab
The New England journal of medicine, Vol.361(11), pp.1067-1074
09/10/2009
DOI: 10.1056/NEJMoa0904267
PMCID: PMC3077718
PMID: 19741227
Abstract
BACKGROUND
Progressive multifocal leukoencephalopathy (PML) occurs in a fraction of patients with multiple sclerosis who were treated with natalizumab. Most adults who are infected with the JC virus, the etiologic agent in PML, do not have symptoms. We sought to determine whether exposure to natalizumab causes subclinical reactivation and neurotropic transformation of JC virus.
METHODS
We followed 19 consecutive patients with multiple sclerosis who were treated with natalizumab over an 18-month period, performing quantitative polymerase-chainreaction assays in blood and urine for JC virus reactivation; BK virus, a JC virus-related polyomavirus, was used as a control. We determined JC virus-specific T-cell responses by means of an enzyme-linked immunospot assay and antibody responses by means of an enzyme-linked immunosorbent assay and analyzed JC virus regulatory-region sequences.
RESULTS
After 12 months of natalizumab therapy, the prevalence of JC virus in the urine of the 19 patients increased from a baseline value of 19% to 63% (P = 0.02). After 18 months of treatment, JC virus was detectable in 3 of 15 available plasma samples (20%) and in 9 of 15 available samples of peripheral-blood mononuclear cells (60%) (P = 0.02). JC virus regulatory-region sequences in blood samples and in most of the urine samples were similar to those usually found in PML. Conversely, BK virus remained stable in urine and was undetectable in blood. The JC virus-specific cellular immune response dropped significantly between 6 and 12 months of treatment, and variations in the cellular immune response over time tended to be greater in patients in whom JC viremia developed. None of the patients had clinical or radiologic signs of PML.
CONCLUSIONS
Subclinical reactivation of JC virus occurs frequently in natalizumab-treated patients with multiple sclerosis. Viral shedding is associated with a transient drop in the JC virus-specific cellular immune response.
Details
- Title: Subtitle
- Asymptomatic Reactivation of JC Virus in Patients Treated with Natalizumab
- Creators
- Yiping Chen - Beth Israel Deaconess Medical CenterEvelyn Bord - Harvard UniversityTroy Tompkins - Harvard UniversityJanice Miller - Harvard UniversityChen S. Tan - Harvard UniversityR. Philip Kinkel - Harvard UniversityMarion C. Stein - Harvard UniversityRaphael P. Viscidi - Johns Hopkins UniversityLong H. Ngo - Harvard UniversityIgor J. Koralnik - Harvard University
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.361(11), pp.1067-1074
- Publisher
- Massachusetts Medical Soc
- DOI
- 10.1056/NEJMoa0904267
- PMID
- 19741227
- PMCID
- PMC3077718
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Number of pages
- 8
- Grant note
- K08NS064215 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) T32AI007061 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01 NS 041198; R01 NS 047029; K24 NS 060950 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 09/10/2009
- Academic Unit
- Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984366291102771
Metrics
12 Record Views