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监测血浆中的 Torque teno 病毒、全微小病毒科和人类 Pegivirus 1 病毒载量,以预测异基因造血干细胞移植中的感染事件和急性移植物抗宿主病。

Monitoring of plasma Torque teno virus, total Anelloviridae and Human Pegivirus 1 viral load for the prediction of infectious events and acute graft versus host disease in the allogeneic hematopoietic stem cell transplantation setting.

机构信息

Microbiology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain.

Hematology Service, Clinic University Hospital, INCLIVA Biomedical Research Institute, Valencia, Spain.

出版信息

J Med Virol. 2023 Sep;95(9):e29107. doi: 10.1002/jmv.29107.

DOI:10.1002/jmv.29107
PMID:37721473
Abstract

Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log (pretransplant) and ≥4.58 log (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD.

摘要

圆环病毒科和人类 Pegivirus 1 (HPgV-1) 的血液负担被认为是移植受者免疫抑制的替代标志物。在这里,我们评估了血浆 Torque teno 病毒 (TTV)、总圆环病毒科 (TAV) 和 HPgV-1 负荷监测对异基因造血干细胞移植受者 (allo-HSCT) 发生感染事件或急性移植物抗宿主病 (aGvHD) 风险增加的潜在应用价值。在这项单中心观察性研究中,监测了 75 例非连续 allo-HSCT 受者(中位年龄 54 岁)的血浆 TTV DNA、TAV DNA 和 HPgV-1 RNA 负荷。监测在移植前或移植后第 30、60、90、120 和 180 天进行。本研究考虑了不同病毒引起的肺炎或卡氏肺孢子虫肺炎、BK 多瘤病毒相关性出血性膀胱炎 (BKPyV-HC) 和巨细胞病毒血症。TTV、TAV DNA 和 HPgV-1 RNA 载量的动力学相似,通过第 30 天和第 90 天(HPgV-1 为第 120 天)测量峰值和峰值水平。40 例患者(53%)在 allo-HSCT 后 180 天内发生了一次或多次感染事件,而 29 例患者(39%)发生了 aGvHD(18 级 II-IV)。TTV、TAV 或 HPgV-1 负荷均不能预测总感染或 CMV 血症。移植前 TTV DNA 负荷≥4.40 log(移植前)和≥4.58 log(基线)拷贝/mL 预测 BKPyV-HC 的发生(敏感性≥89%,阴性预测值≥96%)。第 30 天 TTV DNA 负荷≥3.38 log 预测 aGvHD 的发生(敏感性 90%,阴性预测值 97%)。移植前 HPgV-1 负荷在发生 aGvHD 的患者中明显低于未发生 aGvHD 的患者(p=0.03)。在移植前或移植后早期监测 TTV DNA 或 HPgV-1 RNA 血浆水平可能有助于识别发生 BKPyV-HC 或 aGvHD 风险增加的 allo-HSCT 受者。

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