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ELISpot检测在预测肾移植受者发生BK多瘤病毒肾病风险中的应用:一项多中心研究

Utility of the ELISpot Test to Predict the Risk of Developing BK Polyomavirus Nephropathy in Kidney Recipients, a Multicenter Study.

作者信息

Sempere Abiu, Egri Natalia, Gonzalez Angela, Los-Arcos Ibai, Marcos María Angeles, Bernal-Maurandi Javier, Ruiz-Cabrera Diana, Dieckmann Fritz, Moreso Francesc, Toapanta Néstor, Pascal Mariona, Bodro Marta

机构信息

Department of Infectious Diseases, Vall d'Hebron University Hospital, PROSICS Barcelona, 08035 Barcelona, Spain.

Servei d'Immunologia, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, 08036 Barcelona, Spain.

出版信息

Vaccines (Basel). 2025 Jul 28;13(8):796. doi: 10.3390/vaccines13080796.

DOI:10.3390/vaccines13080796
PMID:40872883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12390299/
Abstract

: BK polyomavirus (BKPyV) reactivation is a common complication after kidney transplantation and may result in nephropathy and graft loss. As there is no effective antiviral therapy, management focuses on early detection and reduction of immunosuppression, which increases the risk of rejection. Identifying patients at higher risk remains challenging. Monitoring BKPyV-specific T-cell responses could aid in predicting reactivation. This study evaluated the usefulness of ELISpot to monitor BKPyV-specific cellular immunity before and after kidney transplantation. : A prospective multicenter study was conducted between October 2020 and March 2022. ELISpot assays were performed prior to transplantation and two months afterward. : Seventy-two patients were included, with a median age of 56 years; 61% were men, and 24% had undergone previous transplantation. Nine patients developed presumptive BKPyV-nephropathy. No significant differences were found in donor type, induction therapy, or rejection rates between patients with or without nephropathy ( = 0.38). Based on ELISpot results, patients were classified into three groups according to their risk of BKPyV-nephropathy. The high-risk group included those who changed from positive to negative at 2 months post-transplant, representing 40% of presumptive BKPyV-nephropathy cases. Patients who remained negative at 2 months were classified as moderate risk (14.5%), while those with a positive ELISpot at 2 months comprised the low-risk group (0%). In the logistic regression analysis, both the ELISpot risk category [OR 19 (CI 1.7-2.08)] and the use of mTOR inhibitors from the start of transplantation [OR 0.02 (CI 0.01-0.46)] were significantly associated with BKPyV-nephropathy. : Monitoring BKPyV-specific T cells with ELISpot before and after kidney transplantation may help stratify patients by risk of reactivation. Loss of BKPyV immunity at two months is associated with nephropathy, while mTOR-based immunosuppression appears protective. This strategy could guide personalized immunosuppression and surveillance.

摘要

BK多瘤病毒(BKPyV)激活是肾移植后常见的并发症,可能导致肾病和移植肾丢失。由于尚无有效的抗病毒治疗方法,管理重点在于早期检测和降低免疫抑制,而这会增加排斥反应的风险。识别高危患者仍然具有挑战性。监测BKPyV特异性T细胞反应有助于预测激活情况。本研究评估了酶联免疫斑点法(ELISpot)在肾移植前后监测BKPyV特异性细胞免疫的效用。

一项前瞻性多中心研究于2020年10月至2022年3月进行。在移植前及移植后两个月进行ELISpot检测。

纳入72例患者,中位年龄56岁;61%为男性,24%曾接受过移植。9例患者发生疑似BKPyV肾病。肾病患者与非肾病患者在供体类型、诱导治疗或排斥率方面未发现显著差异(P = 0.38)。根据ELISpot结果,患者根据其发生BKPyV肾病的风险分为三组。高危组包括移植后2个月从阳性转为阴性的患者,占疑似BKPyV肾病病例的40%。2个月时仍为阴性的患者被分类为中度风险(14.5%),而2个月时ELISpot为阳性的患者构成低风险组(0%)。在逻辑回归分析中,ELISpot风险类别[比值比(OR)19(置信区间[CI] 1.7 - 2.08)]和从移植开始使用雷帕霉素靶蛋白(mTOR)抑制剂[OR 0.02(CI 0.01 - 0.46)]均与BKPyV肾病显著相关。

肾移植前后用ELISpot监测BKPyV特异性T细胞可能有助于根据激活风险对患者进行分层。移植后2个月BKPyV免疫丧失与肾病相关,而基于mTOR的免疫抑制似乎具有保护作用。这一策略可指导个性化免疫抑制和监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/48254831ad65/vaccines-13-00796-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/c74d5b11a31e/vaccines-13-00796-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/9f8ad5ddc105/vaccines-13-00796-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/1dd0d02a6aae/vaccines-13-00796-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/3defdd1ba598/vaccines-13-00796-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/48254831ad65/vaccines-13-00796-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/c74d5b11a31e/vaccines-13-00796-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/9f8ad5ddc105/vaccines-13-00796-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/1dd0d02a6aae/vaccines-13-00796-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/3defdd1ba598/vaccines-13-00796-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ab/12390299/48254831ad65/vaccines-13-00796-g005.jpg

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本文引用的文献

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The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation.《实体器官移植中巨细胞病毒管理的第四届国际共识指南》
Transplantation. 2025 Jul 1;109(7):1066-1110. doi: 10.1097/TP.0000000000005374. Epub 2025 Apr 9.
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BK polyomavirus serotype-specific antibody responses in blood donors and kidney transplant recipients with and without new-onset BK polyomavirus-DNAemia: A Swiss Transplant Cohort Study.瑞士移植队列研究:有无新发BK多瘤病毒血症的献血者和肾移植受者的BK多瘤病毒血清型特异性抗体反应
Am J Transplant. 2025 May;25(5):985-1001. doi: 10.1016/j.ajt.2024.11.019. Epub 2024 Nov 22.
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Insights from the BKEVER Trial comparing everolimus versus mycophenolate mofetil for BK Polyomavirus infection in kidney transplant recipients.
BKEVER试验的见解:比较依维莫司与霉酚酸酯治疗肾移植受者BK多瘤病毒感染的效果
Kidney Int. 2025 Feb;107(2):338-347. doi: 10.1016/j.kint.2024.09.018. Epub 2024 Oct 28.
4
Identification of Candidate Immunodominant Epitopes and Their HLA-Binding Prediction on BK Polyomavirus Proteins in Healthy Donors.在健康供体中鉴定 BK 多瘤病毒蛋白的候选免疫优势表位及其与 HLA-B 结合的预测。
HLA. 2024 Oct;104(4):e15722. doi: 10.1111/tan.15722.
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The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.《肾移植中 BK 多瘤病毒管理的第二届国际共识指南》。
Transplantation. 2024 Sep 1;108(9):1834-1866. doi: 10.1097/TP.0000000000004976. Epub 2024 Apr 12.
6
The incidence of cytomegalovirus and BK polyomavirus infections in kidney transplant patients receiving mTOR inhibitors: A systematic review and meta-analysis.接受 mTOR 抑制剂治疗的肾移植患者中巨细胞病毒和 BK 多瘤病毒感染的发生率:系统评价和荟萃分析。
Pharmacotherapy. 2023 Jun;43(6):552-562. doi: 10.1002/phar.2799. Epub 2023 Apr 10.
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BK Virus and Cytomegalovirus Coinfections in Kidney Transplantation and Their Impact on Allograft Loss.肾移植中的BK病毒与巨细胞病毒合并感染及其对移植肾丢失的影响
J Clin Med. 2021 Aug 24;10(17):3779. doi: 10.3390/jcm10173779.
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Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.依维莫司辅助下降低亚洲肾移植受者中环孢素用量:转化研究亚组分析的 2 年结果。
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Am J Transplant. 2021 Jan;21(1):329-337. doi: 10.1111/ajt.16233. Epub 2020 Aug 27.