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

Abstract：

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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Snyder LD,Chan C,Kwon D,Yi JS,Martissa JA,Copeland CA,Osborne RJ,Sparks SD,Palmer SM,Weinhold KJ

doi

10.1164/rccm.201504-0733OC

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

78-85

issue

eissn

1073-449X

issn

1535-4970

journal_volume

193

pub_type

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