A New Prognostic Score Based on Cell-Mediated Immunity for Cytomegalovirus Infection After Transplantation
Delphine Kervella1,2,3, Franc Casanova-Ferrer2,3, Camille N Kotton4
1Kidney Transplant Unit, Nephrology Department, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Insights
We developed a CMV-PrognosTIC score to predict cytomegalovirus (CMV) infection risk in solid organ transplant (SOT) patients. This score aids in personalizing CMV preventive therapies, improving patient outcomes.
Area of Science:
- Immunology
- Transplant Medicine
- Infectious Disease
Background:
- Cytomegalovirus (CMV) infection is a significant risk for transplant recipients.
- Assessing CMV-specific cell-mediated immunity (CMI) is crucial for identifying at-risk patients.
- Current clinical implementation of CMV-CMI assays like IFN-γ ELISpot faces challenges.
Purpose of the Study:
- To develop a novel CMV-CMI risk-score for predicting CMV infection in solid organ transplant (SOT) patients.
- To create an integrated prognostic system (CMV-PrognosTIC score) for quantifying CMV infection risk.
- To validate the score's clinical utility in guiding personalized preventive therapies.
Main Methods:
- Developed a CMV-CMI risk-score using the standardized T-SPOT.CMV assay targeting CMV antigens IE-1 and pp65.
- Pooled analysis of 570 kidney transplant patients and validation in 146 SOT patients.
- Integrated clinical variables (preventive therapy, age, CMV serostatus) into the score using penalized regression analysis.
Main Results:
- The CMV-CMI risk-score accurately discriminated low-, intermediate-, and high-risk patients for CMV infection (98.7% NPV, 97.2% sensitivity).
- Prospective implementation confirmed high negative predictive value and sensitivity in identifying low-risk patients.
- The global CMV-PrognosTIC model demonstrated accurate discrimination and calibration in both derivation and validation cohorts (AUCs: 0.807 and 0.719).
Conclusions:
- A robust CMV-PrognosTIC score was developed to quantify CMV infection risk in SOT recipients.
- The score can be readily implemented in clinical practice to personalize CMV preventive strategies.
- This approach aims to improve management and outcomes for transplant patients at risk of CMV infection.
Introduction:
The interferon gamma (IFN-γ) enzyme-linked immunosorbent spot is a highly sensitive immune assay that enables the assessment of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) and can identify at-risk transplant patients of CMV infection; however, its clinical implementation remains elusive.
Methods:
We developed a novel CMV-CMI risk-score based on the standardized T-SPOT.CMV assay against 2 CMV antigens (immediate-early protein 1 [IE-1] and 65 kDa phosphoprotein [pp65]), a biomarker predicting CMV infection, both high viral replication, and disease by performing a pooled analysis of 570 kidney transplants participating in different clinical trials and subsequently validating it in 146 consecutives solid organ transplants (SOT) in an interventional trial. By incorporating clinical variables into the CMV-CMI risk-score, we built an integrative prognostic system quantifying the risk of CMV infection (CMV-PrognosTIC score) using elastic net penalized regression analysis.
Results:
In the pooled derivation cohort, whereas specific IE-1/pp65-specific CMV-CMI frequencies independently correlated with high risk of CMV infection (areas under the curve [AUCs]: 0.694, P < 0.0001; 0.719, P < 0.0001, respectively), by combining both responses, 3 CMV-CMI risk-scores appeared, accurately discriminating low-risk (LR) from intermediate-risk (IR) and high-risk (HR) patients (98.7% negative predictive value [NPV], 97.2% sensitivity). Its prospective implementation guiding decision-making in an independent SOT cohort confirmed the very high NPV and sensitivity identifying LR patients. By integrating type of preventive therapy, patient age, and donor (D) and recipient (R) CMV-serostatus to the CMV-CMI risk-score, we generated a global risk-prognostic model showing accurate discrimination and calibration in both derivation (AUC: 0.807) and validation cohorts (AUC: 0.719).
Conclusion:
We developed a robust CMV-PrognosTIC score to quantify the risk of CMV infection in SOT, which may be readily implemented in clinical transplantation to personalize CMV preventive therapies.
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