title: JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.
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.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: Nina
authors.initials: N
authors.lastname: Khanna
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Mueller
authors.forename: Christian
authors.initials: C
authors.lastname: Garzoni
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Raphael
authors.initials: R
authors.lastname: Viscidi
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D015996:Survival Rate
chemical_list: D012367:RNA, Viral