1 Nephrology Service, University Hospital La Paz, Madrid, Spain. 2 Health Research Institute, University Hospital La Paz-IdiPAZ, Madrid, Spain. 3 Address correspondence to: Teresa Bellón, Health Research Institute, University Hospital La Paz-IdiPAZ, Paseo Castellana 261, Madrid, Spain.
Transplantation. 2014 Apr 27;97(8):839-45. doi: 10.1097/01.TP.0000438025.96334.eb.
Cytomegalovirus (CMV) infection is an ongoing clinical problem in solid-organ transplantation (SOT). Pretransplant CMV serology is currently the only tool for assessing the risk of CMV infection, although cellular immune responses driven by CMV-specific CD4 and CD8 T lymphocytes are important for controlling viral replication. Therefore, the analysis of CMV-specific T cells may be useful for estimating the risk of infection.
This is a prospective study of patients with kidney transplants and no prophylactic treatment for CMV replication. CD4 and CD8 T-cell responses to the major CMV pp65 and IE-1 antigens in 15 seropositive patients at intermediate risk of CMV infection were investigated, according to current algorithms. Intracellular flow cytometry was employed to determine IFN-γ production as a functional readout. The response was analyzed in pretransplant samples and prospectively at 1 and 6 months and at 1 year posttransplant.
It was observed that the CD8 responses to IE-1 antigen were practically absent pretransplant in patients who developed CMV infection posttransplant. Within the group of patients free of infection, CD8 responses to IE-1 were detected more frequently and were significantly higher (P=0.0083). In a receiver operating characteristics curve analysis (AUC=0.929; P=0.010; 95% CI: 0.078-1.0), low CD8 responses to IE-1 (≤0.05%) pretransplant predicted the development of CMV infection under the immunosuppressive regime after transplant with 100% specificity and 85.7% sensitivity.
Assessment of IE-1-specific CD8 T-cell frequencies pretransplant may be a useful tool for identifying seropositive SOT patients at risk of developing CMV infection posttransplant.
巨细胞病毒（CMV）感染是实体器官移植（SOT）中的一个持续存在的临床问题。目前，移植前 CMV 血清学是评估 CMV 感染风险的唯一工具，尽管 CMV 特异性 CD4 和 CD8 T 淋巴细胞驱动的细胞免疫反应对于控制病毒复制很重要。因此，CMV 特异性 T 细胞的分析可能有助于估计感染风险。
这是一项对接受肾移植且无 CMV 复制预防性治疗的患者的前瞻性研究。根据现行算法，研究了 15 名 CMV 感染中危的血清阳性患者的 CMV 主要 pp65 和 IE-1 抗原的 CD4 和 CD8 T 细胞反应。采用细胞内流式细胞术测定 IFN-γ的产生作为功能读数。在移植前样本中进行了分析，并在移植后 1、6 个月和 1 年进行了前瞻性分析。
研究观察到，在移植后发生 CMV 感染的患者中，移植前 IE-1 抗原的 CD8 反应实际上不存在。在未感染组患者中，IE-1 的 CD8 反应检测到的频率更高，且显著更高（P=0.0083）。在接受者操作特征曲线分析（AUC=0.929；P=0.010；95%CI：0.078-1.0）中，移植前 IE-1 的低 CD8 反应（≤0.05%）预测了移植后免疫抑制治疗下 CMV 感染的发生，特异性为 100%，敏感性为 85.7%。
移植前评估 IE-1 特异性 CD8 T 细胞频率可能是识别移植后发生 CMV 感染风险的血清阳性 SOT 患者的有用工具。
