JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy.
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.
Khanna
Nina
N
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, CH-4031 Basel, Switzerland.
Wolbers
Marcel
M
Mueller
Nicolas J
NJ
Garzoni
Christian
C
Du Pasquier
Renaud A
RA
Fux
Christoph A
CA
Vernazza
Pietro
P
Bernasconi
Enos
E
Viscidi
Raphael
R
Battegay
Manuel
M
Hirsch
Hans H
HH
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
D012367:RNA, Viral