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. 2025 Jan 10:e14437.
doi: 10.1111/tid.14437. Online ahead of print.

Diagnostic Performance of Two Different Techniques to Quantify CMV-Specific Cell-Mediated Immunity in Intermediate-Risk Seropositive Kidney Transplant Recipients

Mario Fernández-Ruiz  1   2   3 , Marcos Nuévalos  4 , Isabel Rodríguez-Goncer  1   2   3 , Estéfani García-Ríos  5 , Tamara Ruiz-Merlo  1   2 , Natalia Redondo  1   2 , Hernando Trujillo  6 , Esther González  6 , Natalia Polanco  6 , José María Caso  1 , Eduardo Aparicio-Minguijón  1 , Francisco López-Medrano  1   2   3 , Rafael San Juan  1   2   3 , Amado Andrés  3   6 , Pilar Pérez-Romero  7 , José María Aguado  1   2   3
Affiliations

Diagnostic Performance of Two Different Techniques to Quantify CMV-Specific Cell-Mediated Immunity in Intermediate-Risk Seropositive Kidney Transplant Recipients

Mario Fernández-Ruiz et al. Transpl Infect Dis. .

Abstract

Background: Kidney transplant (KT) recipients at intermediate risk for cytomegalovirus (CMV) infection constitute a potential target for individualized prevention strategies informed by the CMV-specific cell-mediated immunity (CMV-CMI). The optimal method for the functional assessment of CMV-CMI in this group remains unclear.

Methods: We included 74 CMV-seropositive KT recipients that did not receive T-cell-depleting induction and were managed by preemptive therapy. CMV-CMI was monitored at baseline and months 1, 3, 6, and 12 by intracellular cytokine staining (ICS) and a interferon (IFN)-γ-release assay (QuantiFERON-CMV [QTF-CMV]). Both methods were compared for discriminative capacity (areas under the receiving operating characteristic curve [auROCs]) and diagnostic accuracy to predict protection against high-level (≥1000 IU/mL) CMV DNAemia and/or disease.

Results: Eighteen patients (24.3%) experienced high-level CMV DNAemia or disease. There were no significant differences in the discriminative capacity to predict protection of CMV-specific CD8+ (auROC: 0.719) and CD4+ T-cell counts (auROC: 0.664) enumerated by ICS and IFN-γ production measured by QTF-CMV (auROC: 0.666). Optimal cutoff values of ≥9.8 CMV-specific CD4+ T-cells/µL and ≥5.7 CD8+ T-cells/µL by ICS yielded excellent specificity (95.7% and 86.9%, respectively) and positive predictive values (PPVs) (>98.0%), but a sensitivity below 60%. A reactive QTF-CMV (IFN-γ ≥0.2 IU/mL) provided good sensitivity (81.6%) and PPV (92.5%), at the expense of a poor specificity (22.2%).

Conclusions: The discriminative capacity to predict immune protection against clinically relevant CMV infection among intermediate-risk KT recipients was comparable for ICS and QTF-CMV. A selected ICS threshold may provide better specificity than the interpretative cut-off values currently recommended for QTF-CMV.

Keywords: QuantiFERON‐CMV; cell‐mediated immunity; cytomegalovirus; intermediate risk; intracellular cytokine staining; kidney transplantation; seropositive.

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References

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