Poor predictive value of cytomegalovirus (CMV)-specific T cell assays for the development of CMV retinitis in patients with AIDS.
BACKGROUND
We examined the potential clinical utility of using a cytomegalovirus (CMV)-specific T cell immunoassay to determine the risk of developing new-onset CMV retinitis (CMVR) in patients with acquired immunodeficiency syndrome (AIDS).


METHODS
CMV-specific T cell assays were performed by multiparameter flow cytometry using stored peripheral blood mononuclear cells that had been obtained in an observational study 2-6 months before new-onset CMVR was diagnosed in case patients (at a study visit during which a dilated ophthalmologic examination revealed no evidence of CMVR) and at the same study visit in control subjects (matched by absolute CD4(+) T cell count at entry) who did not subsequently develop retinitis during 1-6 years of study follow-up.


RESULTS
There were no significant differences in CMV-specific CD4(+) or CD8(+) T cell interferon-gamma or interleukin-2 expression in peripheral blood mononuclear cells from case patients and control subjects. Although there were trends toward lower percentages and absolute numbers of CMV-specific, cytokine-expressing CD8(+) T cells with a "late memory" phenotype (CD27(-)CD28(-)) as well as with an "early memory" phenotype (CD27(+)CD28(+)CD45RA(+)) in case patients than in control subjects, these differences were not statistically significant.


CONCLUSIONS
Many studies have reported that CMV-specific CD4(+) and CD8(+) T cell responses distinguish patients with active CMVR (i.e., who lack CMV-protective immunity) from those with inactive CMVR after immune restoration by antiretroviral treatment (i.e., who have CMV-protective immunity). However, the multiple CMV-specific immune responses we measured do not appear to have clinical utility for predicting the risk for patients with AIDS of developing new-onset CMVR with sufficient accuracy to be used in guiding therapeutic management.
Jacobson
Mark A
MA
Positive Health Program, Department of Medicine, University of California San Francisco, CA, USA. mjacobson@php.ucsf.edu
Tan
Qi Xuan
QX
Girling
Valerie
V
Poon
C
C
Van Natta
Mark
M
Jabs
Douglas A
DA
Inokuma
Margaret
M
Maecker
Holden T
HT
Bredt
Barry
B
Sinclair
Elizabeth
E
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D017726:Cytomegalovirus Retinitis / Q000276:immunology* / Q000821:virology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma