BACKGROUND Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events. METHODS Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. RESULTS We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65-96%), and negative predictive value (NPV) was 67% (95%CI 41-87%). CONCLUSIONS The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.

中文翻译：

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通过流式细胞术和细胞内细胞因子染色来预测临床上显着的巨细胞病毒事件的新方法检测巨细胞病毒（CMV）特异性CD4 +和CD8 + T细胞免疫力的临床经验。

背景技术尽管给予CMV预防，但巨细胞病毒（CMV）感染是器官移植后最常见的机会感染之一。CMV特异性T细胞免疫（TCI）与CMV感染率降低相关。我们首次描述了使用CMV T细胞免疫小组（CMV-TCIP）的临床经验，CMV T细胞免疫小组是一种可测量CMV特异性CD4 +和CD8 + T细胞反应，以预测临床上显着的CMV事件的商业化检测方法。方法布朗大学和马里兰大学医学中心附属医院于4/2017年至5/2019年纳入具有CMV-TCIP结果且≥1次随后的CMV DNA血症评估的成年（> 18岁）患者。具有临床意义的CMV事件定义为提示开始治疗的CMV DNAemia。我们排除不确定的结果，主要是由于背景阳性，同种异体造血细胞移植（HCT）受者或继续接受针对CMV的抗病毒治疗的患者，而与CMV-TCIP结果无关，因为正在进行的抗病毒治疗可以预防CMV事件。结果我们分析了37例患者的44份样本：31例为实体器官移植受者，4例患有血液系统恶性肿瘤，2例患有自身免疫性疾病。曲线（AUC）下的CMV保护接收器工作特征（ROC）区域对于％CMV特异性CD4 +（AUC：0.78，P <0.001）和CD8 +（AUC：0.66，P = 0.064）T细胞具有显着意义。在CMV特异性CD4 + T细胞的临界值为0.22％时，针对CMV的保护的阳性预测值（PPV）为85％（95％CI 65-96％），阴性预测值（NPV）为67％ （95％CI 41-87％）。结论CMV-TCIP，特别是％CMV特异性CD4 + T细胞，表现出良好的诊断性能，可预测CMV事件。CMV-TCIP在临床实践中可能是有用的测试，并且在较大的前瞻性研究中值得进一步验证。