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JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy

Khanna, Nina and Wolbers, Marcel and Mueller, Nicolas J. and Garzoni, Christian and Du Pasquier, Renaud A. and Fux, Christoph A. and Vernazza, Pietro and Bernasconi, Enos and Viscidi, Raphael and Battegay, Manuel and Hirsch, Hans H.. (2009) JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy. Journal of virology, Vol. 83. pp. 4404-4411.

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Official URL: http://edoc.unibas.ch/dok/A6003724

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Abstract

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for <1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Infektiologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Infektiologie
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Infection Biology (Khanna)
03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Transplantation Virology (Hirsch)
UniBasel Contributors:Battegay, Manuel E. and Hirsch, Hans H. and Khanna, Nina
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:0022-538X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:13
Deposited On:01 Mar 2013 11:09

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