Article: article from journal or magazin.
JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.
Journal of Virology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Adult, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/pathology, Cell Proliferation, Cytomegalovirus/immunology, Disease Progression, Female, HIV Infections/complications, HIV Infections/epidemiology, HIV-1/genetics, HIV-1/immunology, Humans, JC Virus/immunology, Leukoencephalopathy, Progressive Multifocal/complications, Leukoencephalopathy, Progressive Multifocal/epidemiology, Male, Middle Aged, RNA, Viral/genetics, Survival Rate
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