Skip to main content

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.

Publication ,  Journal Article
Snyder, LD; Chan, C; Kwon, D; Yi, JS; Martissa, JA; Copeland, CAF; Osborne, RJ; Sparks, SD; Palmer, SM; Weinhold, KJ
Published in: Am J Respir Crit Care Med
January 1, 2016

RATIONALE: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects. OBJECTIVES: We sought to identify a specific immunologic signature that predicted protection from subsequent CMV. METHODS: CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort. MEASUREMENTS AND MAIN RESULTS: Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]). The model included both protective (CD107a(-)/IFN-γ(+)/IL-2(+)/TNF-α(+) CD4(+) T cells, CD107a(-)/IFN-γ(+)/IL-2(+)/TNF-α(+) CD8(+) T cells) and detrimental (CD107a(+)/IFN-γ(+)/IL-2(-)/TNF-α(-) CD8(+) T cells) subsets. The model was robust in the validation cohort (concordance index 0.81 [SE, 0.103]). CONCLUSIONS: We identified and validated a specific T-cell polyfunctional response to CMV antigen stimulation that provides a clinically useful prediction of subsequent cytomegalovirus risk. This novel diagnostic approach could inform the optimal duration of individual prophylaxis.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Respir Crit Care Med

DOI

EISSN

1535-4970

Publication Date

January 1, 2016

Volume

193

Issue

1

Start / End Page

78 / 85

Location

United States

Related Subject Headings

  • Viremia
  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes
  • Risk Factors
  • Respiratory System
  • Proportional Hazards Models
  • Middle Aged
  • Male
  • Lysosomal-Associated Membrane Protein 1
  • Lung Transplantation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Snyder, L. D., Chan, C., Kwon, D., Yi, J. S., Martissa, J. A., Copeland, C. A. F., … Weinhold, K. J. (2016). Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. Am J Respir Crit Care Med, 193(1), 78–85. https://doi.org/10.1164/rccm.201504-0733OC
Snyder, Laurie D., Cliburn Chan, Darongsae Kwon, John S. Yi, Jessica A. Martissa, C Ashley Finlen Copeland, Robyn J. Osborne, Sara D. Sparks, Scott M. Palmer, and Kent J. Weinhold. “Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.Am J Respir Crit Care Med 193, no. 1 (January 1, 2016): 78–85. https://doi.org/10.1164/rccm.201504-0733OC.
Snyder LD, Chan C, Kwon D, Yi JS, Martissa JA, Copeland CAF, et al. Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. Am J Respir Crit Care Med. 2016 Jan 1;193(1):78–85.
Snyder, Laurie D., et al. “Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation.Am J Respir Crit Care Med, vol. 193, no. 1, Jan. 2016, pp. 78–85. Pubmed, doi:10.1164/rccm.201504-0733OC.
Snyder LD, Chan C, Kwon D, Yi JS, Martissa JA, Copeland CAF, Osborne RJ, Sparks SD, Palmer SM, Weinhold KJ. Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. Am J Respir Crit Care Med. 2016 Jan 1;193(1):78–85.

Published In

Am J Respir Crit Care Med

DOI

EISSN

1535-4970

Publication Date

January 1, 2016

Volume

193

Issue

1

Start / End Page

78 / 85

Location

United States

Related Subject Headings

  • Viremia
  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes
  • Risk Factors
  • Respiratory System
  • Proportional Hazards Models
  • Middle Aged
  • Male
  • Lysosomal-Associated Membrane Protein 1
  • Lung Transplantation