Renal Transplantation Unit, Nephrology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, 2790-134 Carnaxide, Portugal.
Infection, Sepsis & Antibiotics Resistance Research Group, CHRC-Comprehensive Health Research Center, NOVA Medical School, Faculdade de Ciências Médicas (NMS|FCM), Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal.
Viruses. 2023 Jun 28;15(7):1464. doi: 10.3390/v15071464.
Torque teno virus (TTV) was recently identified as a potential biomarker for the degree of immunosuppression, and potentially as a predictor of rejection and infection in solid organ transplant patients. We evaluated TTV viral load in kidney transplant (KT) patients during the first year post-transplant to examine overall kinetics and their relationships with deleterious events, including episodes of infection and the formation of de novo donor-specific antibodies (DSAs). In a single-center, prospective observational cohort study, 81 KT patients were monitored at baseline, week 1, and month 1, 3, 6, 9 and 12, post-KT, and whenever required by clinical events. Kidney function, plasma TTV load, immunoglobulins and lymphocyte subpopulations were assessed at each time point. Twenty-six patients (32.1%) presented a total of 38 infection episodes post-KT. Induction immunosuppression with thymoglobulin, compared to basiliximab, was not associated with more infections ( = 0.8093). Patients with infectious events had lower T-cells ( = 0.0500), CD8 T-cells ( = 0.0313) and B-cells ( = 0.0009) 1 month post-KT, compared to infection-free patients. Patients with infection also showed higher increases in TTV viral loads between week 1- month 1, post-KT, with TTV viral load variations >2.65 log cp/mL predicting the development of infectious events during the 12-month study period ( < 0.0001; sensitivity 99.73%; specificity 83.67%). Patients who developed de novo DSAs had lower TTV DNA viral loads at month 12 after KT, compared to patients who did not develop DSA (3.7 vs. 5.3 log cp/mL, = 0.0023). Briefly, evaluating early TTV viremia is a promising strategy for defining infectious risk in the 1st year post-KT. The availability of standardized commercial real-time PCR assays is crucial to further validate this as an effective tool guiding immunosuppression prescription.
Torque teno 病毒 (TTV) 最近被确定为免疫抑制程度的潜在生物标志物,并且可能是实体器官移植患者排斥和感染的预测因子。我们评估了移植后第一年的肾移植 (KT) 患者的 TTV 病毒载量,以检查总体动力学及其与有害事件的关系,包括感染发作和新形成的供体特异性抗体 (DSA)。在一项单中心前瞻性观察队列研究中,81 名 KT 患者在移植后第 1 周、第 1、3、6、9 和 12 个月以及临床事件需要时进行监测。在每个时间点评估肾功能、血浆 TTV 载量、免疫球蛋白和淋巴细胞亚群。26 名患者(32.1%)共发生 38 次 KT 后感染。与巴利昔单抗相比,使用胸腺球蛋白进行诱导免疫抑制与更多感染无关( = 0.8093)。与无感染患者相比,发生感染事件的患者在 KT 后 1 个月时 T 细胞( = 0.0500)、CD8 T 细胞( = 0.0313)和 B 细胞( = 0.0009)较低。发生感染的患者在 KT 后第 1 周到第 1 个月之间的 TTV 病毒载量也有更高的增加,TTV 病毒载量变化 >2.65 log cp/mL 预测在 12 个月研究期间发生感染事件(<0.0001;敏感性 99.73%;特异性 83.67%)。与未发生 DSA 的患者相比,发生新的 DSA 的患者在 KT 后 12 个月时的 TTV DNA 病毒载量较低(3.7 与 5.3 log cp/mL, = 0.0023)。简而言之,评估早期 TTV 病毒血症是定义 KT 后 1 年内感染风险的有前途的策略。可获得标准化的商业实时 PCR 检测对于进一步验证这一方法作为指导免疫抑制处方的有效工具至关重要。