Casas-Parra Angela, Veltman Hendrik, Romero-Caballero Alba, Gelpi-Remiro Rosana, Boigues-Pons Marc, Allalou Imán, Linares-Pardo Ian, Vila-Santandreu Anna, Martínez-Cáceres Eva, Iglesias-Escudero María
Division of Nephrology, Germans Trias i Pujol University Hospital, Badalona, Spain.
Germans Trias I Pujol Research Institute (IGTP), Badalona, Spain.
Front Immunol. 2025 May 16;16:1567253. doi: 10.3389/fimmu.2025.1567253. eCollection 2025.
CMV infection is the most prevalent opportunistic infection following solid organ transplantation (SOT), significantly affecting both graft and patient survival. Effective control of viral replication is crucial to prevent CMV infection from progressing to end-organ disease. Despite its high prevalence, options for preventing CMV infection and end-organ disease are limited to a few antiviral drugs, which have severe side effects and may lead to resistance. In this context, measuring CMV-specific cell-mediated immunity (CMI) has proven to be a valuable tool, with high negative predictive value (NPV) for the absence of CMV viremia in patients with positive tests. This study aimed to evaluate the sensitivity and specificity of various cellular immune response assays and assess the feasibility of incorporating them into routine clinical practice for kidney transplant recipients (KTR). Conducted at the Hospital Universitari Germans Trias i Pujol (HGTP), the study analyzed 56 samples from KTR and 10 healthy controls (HC). Patients and controls were classified based on their pre-transplant serostatus, and CMI was measured using QuantiFERON-CMV ELISA, T cell proliferation assay (TCPA), activation-induced marker (AIM) assay, and an in-house ELISA. The AIM assay demonstrated that CD69 is a reliable activation marker for flow cytometry-based assays, as it consistently increased following polyclonal stimulation. Notably, among the total patient cohort with CD4 T cell reactivity, the CM subpopulation exhibited the most significant increase (p < 0.001). Comparative analysis revealed that both ELISAs had high sensitivity and specificity compared to other techniques. The consistency test results showed perfect and almost perfect agreement between the AIM (cut-off 0.2) and the QuantiFERON-CMV ELISA and in-house ELISA, respectively. The study also explored the feasibility of incorporating these tests into daily clinical practice, proposing an algorithm based on test results and cost-effectiveness. This algorithm involves testing patients using the QuantiFERON-CMV assay, followed by AIM testing in cases of indeterminate results or HLA mismatches. Incorporating these assays would help identify patients at the lowest risk of CMV infection after prophylaxis, enabling more selective and personalized prophylactic strategies.
巨细胞病毒（CMV）感染是实体器官移植（SOT）后最常见的机会性感染，对移植物和患者的存活均有显著影响。有效控制病毒复制对于防止CMV感染发展为终末器官疾病至关重要。尽管其患病率很高，但预防CMV感染和终末器官疾病的选择仅限于少数几种抗病毒药物，这些药物有严重的副作用且可能导致耐药。在这种情况下，测量CMV特异性细胞介导免疫（CMI）已被证明是一种有价值的工具，对于检测结果呈阳性的患者，其对无CMV病毒血症具有较高的阴性预测值（NPV）。本研究旨在评估各种细胞免疫反应检测方法的敏感性和特异性，并评估将其纳入肾移植受者（KTR）常规临床实践的可行性。该研究在德国特里亚斯-普尤尔大学医院（HGTP）进行，分析了56份KTR样本和10份健康对照（HC）样本。患者和对照根据移植前血清学状态进行分类，并使用QuantiFERON-CMV ELISA、T细胞增殖试验（TCPA）、激活诱导标志物（AIM）试验和一种内部ELISA检测CMI。AIM试验表明，CD69是基于流式细胞术检测的可靠激活标志物，因为在多克隆刺激后它持续增加。值得注意的是，在具有CD4 T细胞反应性的全部患者队列中，CM亚群的增加最为显著（p < 0.001）。比较分析显示，与其他技术相比，两种ELISA均具有较高的敏感性和特异性。一致性检验结果表明，AIM试验（临界值为0.2）与QuantiFERON-CMV ELISA和内部ELISA之间分别具有完美和几乎完美的一致性。该研究还探讨了将这些检测纳入日常临床实践的可行性，根据检测结果和成本效益提出了一种算法。该算法包括使用QuantiFERON-CMV检测法对患者进行检测，对于结果不确定或存在HLA不匹配的情况，随后进行AIM检测。纳入这些检测将有助于识别预防后CMV感染风险最低的患者，从而实现更具选择性和个性化的预防策略。
