移植后巨细胞病毒感染基于细胞介导免疫的新预后评分

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports Pub Date : 2025-09-01 DOI:10.1016/j.ekir.2025.06.056

Delphine Kervella , Franc Casanova-Ferrer , Camille N. Kotton , Laura Donadeu , Deepali Kumar , Silvia Pineda , Elena Crespo , Maria Meneghini , José González-Costelo , Elena García-Romero , Laura Lladó , Alba Cachero , Edoardo Melilli , Irina B. Torres , Anna Martínez-Lacalle , Zaira Castañeda , Mónica Martinez-Gallo , Oscar Len , Ibai Los-Arcos , Enric Trilla-Herrera , Oriol Bestard

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引用次数: 0

摘要

干扰素γ (IFN-γ)酶联免疫吸附点是一种高度敏感的免疫测定方法，可用于评估巨细胞病毒（CMV）特异性细胞介导免疫（CMI），并可识别CMV感染的高危移植患者；然而，其临床应用仍然难以捉摸。方法建立一种基于标准化T-SPOT的CMV-CMI风险评分。针对2种巨细胞病毒抗原（即早期蛋白1 [ee -1]和65 kDa磷酸化蛋白[pp65]）的巨细胞病毒检测，这是一种预测巨细胞病毒感染、高病毒复制和疾病的生物标志物，通过对参与不同临床试验的570例肾移植进行合并分析，随后在一项介入性试验中对146例连续实体器官移植（SOT）进行验证。通过将临床变量纳入CMV- cmi风险评分，我们使用弹性网惩罚回归分析建立了一个量化CMV感染风险的综合预后系统（CMV- prognostic评分）。结果在合并衍生队列中，虽然特定的ee -1/pp65特异性CMV- cmi频率与CMV感染的高风险独立相关（曲线下面积[aus]分别为0.694,P < 0.0001; 0.719, P < 0.0001），但通过结合两种反应，出现了3个CMV- cmi风险评分，准确区分了低危（LR）、中危（IR）和高危（HR）患者（阴性预测值[NPV]为98.7%，敏感性为97.2%）。其在独立SOT队列中指导决策的前瞻性实施证实了非常高的NPV和识别LR患者的敏感性。通过将预防治疗类型、患者年龄、供体(D)和受体(R) cmv血清状态整合到CMV-CMI风险评分中，我们生成了一个全球风险-预后模型，在推导（AUC: 0.807）和验证队列（AUC: 0.719）中都显示出准确的区分和校准。结论：我们开发了一个强大的CMV预后评分来量化SOT中CMV感染的风险，这可能很容易在临床移植中实施个体化CMV预防治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A New Prognostic Score Based on Cell-Mediated Immunity for Cytomegalovirus Infection After Transplantation

查看原文本刊更多论文

A New Prognostic Score Based on Cell-Mediated Immunity for Cytomegalovirus Infection After Transplantation

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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来源期刊

Kidney International Reports Medicine-Nephrology

CiteScore

7.70

自引率

3.30%

发文量

1578

审稿时长

8 weeks

期刊介绍： Kidney International Reports, an official journal of the International Society of Nephrology, is a peer-reviewed, open access journal devoted to the publication of leading research and developments related to kidney disease. With the primary aim of contributing to improved care of patients with kidney disease, the journal will publish original clinical and select translational articles and educational content related to the pathogenesis, evaluation and management of acute and chronic kidney disease, end stage renal disease (including transplantation), acid-base, fluid and electrolyte disturbances and hypertension. Of particular interest are submissions related to clinical trials, epidemiology, systematic reviews (including meta-analyses) and outcomes research. The journal will also provide a platform for wider dissemination of national and regional guidelines as well as consensus meeting reports.