Rodrigo Emilio, González-López Elena, Ocejo-Vinyals Javier Gonzalo, Pasache Enrique, García-Majado Cristina, López Del Moral Covadonga, García-Santiago Ana, Benito-Hernández Adalberto, Francia María Victoria, Ruiz Juan Carlos
Immunopathology Group, Nephrology Department, Marqués de Valdecilla University Hospital-IDIVAL, University of Cantabria, 39005 Santander, Spain.
Immunopathology Group, Immunology Department, Marqués de Valdecilla University Hospital-IDIVAL, University of Cantabria, 39005 Santander, Spain.
J Clin Med. 2025 Apr 1;14(7):2417. doi: 10.3390/jcm14072417.
: New monitoring methods are being developed to improve the kidney transplant outcome. Among them, the measurement of Torque Teno virus load (TTV load) has been associated with the overall immunosuppressive status and the percentage of donor-derived circulating free DNA (dd-cfDNA) with molecular graft injury, mainly related to antibody-mediated rejection (AbMR). Both methods provide complementary information, but they have not been previously used together for the monitoring of kidney transplant recipients (KTx). : A prospective study including 42 KTx performed in our centre was conducted, in which we monitored dd-cfDNA using a targeted NGS assay (AlloSeq cfDNA) in the first month and the TTV load with in-house PCR in the first and third months. : Eleven KTx with high molecular injury defined by dd-cfDNA ≥ 1.0% were selected. The TTV load showed a non-significant trend of being lower in AbMR patients (2.91, IQR 4.18 vs. 3.48, IQR 1.47 log10 copies/mL, = 0.788). No overimmunosuppressed patient developed AbMR, whereas 40% of non-overimmunosuppressed patients showed AbMR ( = 0.428). The TTV load increased more in the AbMR-treated KTx (0.00, IQR 4.71 vs. +6.58, IQR 4.04 log10 copies/mL, = 0.042) from months one to three, with all AbMR-treated KTx becoming overimmunosuppressed. KTx with opportunistic infections showed higher TTV loads in the third month (5.18, IQR 5.92 vs. 11.53, IQR 3.54 log10 copies/mL, = 0.024). : KTx with molecular injury secondary to rejection tended to be less immunosuppressed, as indicated by a low TTV load. After AbMR therapy, all KTx became overimmunosuppressed and suffered a higher risk of opportunistic infections. Dual monitoring provides useful complementary information for the follow-up of kidney transplant recipients.
正在开发新的监测方法以改善肾移植结果。其中，Torque Teno病毒载量（TTV载量）的测定与整体免疫抑制状态相关，而供体来源的循环游离DNA（dd-cfDNA）百分比与分子移植损伤相关，主要与抗体介导的排斥反应（AbMR）有关。这两种方法提供互补信息，但此前尚未一起用于监测肾移植受者（KTx）。
我们中心进行了一项前瞻性研究，纳入了42例KTx，在第一个月使用靶向NGS检测（AlloSeq cfDNA）监测dd-cfDNA，在第一个月和第三个月使用内部PCR检测TTV载量。
选择了11例由dd-cfDNA≥1.0%定义为高分子损伤的KTx。TTV载量在AbMR患者中呈非显著降低趋势（2.91，四分位距4.18 vs. 3.48，四分位距1.47 log10拷贝/mL，P = 0.788）。没有免疫抑制过度的患者发生AbMR，而40%免疫抑制未过度的患者出现AbMR（P = 0.428）。从第一个月到第三个月，接受AbMR治疗的KTx中TTV载量增加更多（0.00，四分位距4.71 vs. +6.58，四分位距4.04 log10拷贝/mL，P = 0.042），所有接受AbMR治疗的KTx都出现了免疫抑制过度。发生机会性感染的KTx在第三个月显示出更高的TTV载量（5.18，四分位距5.92 vs. 11.53，四分位距3.54 log10拷贝/mL，P = 0.024）。
排斥反应继发分子损伤的KTx往往免疫抑制程度较低，表现为TTV载量较低。AbMR治疗后，所有KTx都出现了免疫抑制过度，且发生机会性感染的风险更高。双重监测为肾移植受者的随访提供了有用的互补信息。
