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Torque Teno 病毒用于肾移植受者急性经活检证实的同种异体反应的风险分层。

Torque Teno Virus for Risk Stratification of Acute Biopsy-Proven Alloreactivity in Kidney Transplant Recipients.

机构信息

Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Austria.

Division of Transplant Surgery, Department of Surgery, Medical University Vienna, Austria.

出版信息

J Infect Dis. 2019 May 24;219(12):1934-1939. doi: 10.1093/infdis/jiz039.

DOI:10.1093/infdis/jiz039
PMID:30668796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6534191/
Abstract

BACKGROUND

Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring.

METHODS

We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction.

RESULTS

Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84-.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity.

CONCLUSIONS

TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy.

摘要

背景

肾移植受者的药物诱导免疫抑制对于预防移植物排斥至关重要,但会增加感染性疾病的风险。免疫监测以调整免疫抑制药物的剂量可能同时预防同种异体反应和不良反应。无致病性的绞链酶切细小病毒(TTV)反映了宿主的免疫能力,可能是一种潜在的整体监测候选物。

方法

我们筛选了前瞻性维也纳肾移植队列研究中的 1010 例连续患者,以确定是否有足够的同种异体移植活检和储存血清,以便通过聚合酶链反应定量 TTV。

结果

根据 Banff 分类,在活检前中位数为 43 天,有急性活检证实的同种异体反应(n = 33)的患者外周血中的 TTV 水平低于无排斥反应的患者(n = 80)。TTV 拷贝/ml 每增加一个对数水平,同种异体反应的风险降低 10%(风险比,0.90 [95%置信区间,0.84-0.97];P = 0.005)。TTV 水平 >1×106 拷贝/ml 可排除排斥反应,其灵敏度为 94%。多变量广义线性模型表明 TTV 水平与同种异体反应之间存在独立关联。

结论

TTV 是肾移植受者急性活检证实的同种异体反应风险分层的前瞻性生物标志物,可能是调整免疫抑制药物治疗的潜在工具。

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Am J Transplant. 2019 Apr;19(4):1139-1149. doi: 10.1111/ajt.15145. Epub 2018 Nov 10.
2
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J Infect Dis. 2018 Nov 5;218(12):1922-1928. doi: 10.1093/infdis/jiy452.
3
Quantification of Torque Teno Virus Viremia as a Prospective Biomarker for Infectious Disease in Kidney Allograft Recipients.定量检测 Torque Teno 病毒血症作为肾移植受者感染性疾病的潜在生物标志物。
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4
Evaluation of a Novel Global Immunity Assay to Predict Infection in Organ Transplant Recipients.新型全免疫检测预测器官移植受者感染的评估。
Clin Infect Dis. 2018 Apr 17;66(9):1392-1397. doi: 10.1093/cid/cix1008.
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Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients.肾移植患者中与他克莫司治疗药物监测相关的药代动力学考量
Expert Opin Drug Metab Toxicol. 2017 Dec;13(12):1225-1236. doi: 10.1080/17425255.2017.1395413. Epub 2017 Oct 30.
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