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

Nina Khanna, Marcel Wolbers, Nicolas J. Mueller, Christian Garzoni, Renaud A. Du Pasquier, Christoph A. Fux, Pietro Vernazza, Enos Bernasconi, Raphael Viscidi, Manuel Battegay, Hans H. Hirsch

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4404-4411
Number of pages8
JournalJournal of virology
Volume83
Issue number9
DOIs
StatePublished - May 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Khanna, N., Wolbers, M., Mueller, N. J., Garzoni, C., Du Pasquier, R. A., Fux, C. A., Vernazza, P., Bernasconi, E., Viscidi, R., Battegay, M., & Hirsch, H. H. (2009). JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy. Journal of virology, 83(9), 4404-4411. https://doi.org/10.1128/JVI.02657-08