Poor predictive value of cytomegalovirus (CMV)-specific T cell assays for the development of CMV retinitis in patients with AIDS

Clin Infect Dis. 2008 Feb 1;46(3):458-66. doi: 10.1086/525853.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Cytomegalovirus Retinitis / immunology*
  • Cytomegalovirus Retinitis / virology*
  • Female
  • Flow Cytometry / methods
  • Humans
  • Immediate-Early Proteins / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Phosphoproteins / immunology
  • Predictive Value of Tests
  • T-Lymphocytes / immunology*
  • Viral Matrix Proteins / immunology
  • Viral Proteins / immunology

Substances

  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Interleukin-2
  • Phosphoproteins
  • Viral Matrix Proteins
  • Viral Proteins
  • cytomegalovirus matrix protein 65kDa
  • Interferon-gamma

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