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移植前BK病毒特异性T细胞介导的免疫和血清型特异性抗体可能有助于识别异基因造血干细胞移植后发生BK病毒相关出血性膀胱炎的风险患者。

Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT.

作者信息

Šťastná-Marková Markéta, Hamšíková Eva, Hainz Petr, Hubáček Petr, Kroutilová Marie, Kryštofová Jitka, Ludvíková Viera, Musil Jan, Pecherková Pavla, Saláková Martina, Šroller Vojtěch, Vydra Jan, Němečková Šárka

机构信息

Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic.

Laboratory of Virology, Motol Hospital, 150 06 Prague, Czech Republic.

出版信息

Vaccines (Basel). 2021 Oct 22;9(11):1226. doi: 10.3390/vaccines9111226.

Abstract

BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st-2nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with "non-reactive" anti-BKPyV IgG levels and with low clinical risk (LCR) ( = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-γ T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease.

摘要

BK多瘤病毒(BKPyV)在肾细胞和尿路上皮细胞中终身潜伏,健康个体尿液中会无症状排出该病毒。在一些造血干细胞移植(HSCT)后的免疫功能低下者中,BKPyV的高复制率与出血性膀胱炎(HC)有关。我们测试了HSCT前BKPyV免疫状态是否能为BKPyV重新激活的倾向提供证据。我们发现,测量移植前抗BKPyV 1和4 IgG水平可用于评估HC风险。与抗BKPyV IgG水平“无反应”且临床风险低(LCR)的参考组患者相比,抗BKPyV IgG处于阳性值第1-2四分位数范围内且有阳性临床风险标志物的患者,其HC风险显著增加( = 0.0009)。通过对排出病毒的基因型测定,证实了移植前BKPyV特异性IgG的预测价值。还发现移植前针对BKPyV抗原VP1的T细胞免疫具有阳性预测价值,因为IFN-γ T细胞反应的强度与移植后病毒尿和HC呈负相关。我们的新数据表明,特定的T细胞在HSCT前控制BKPyV潜伏,从而可能影响HSCT后BKPyV的重新激活。我们的研究表明,结合临床和移植前免疫危险因素进行预测有助于早期识别BKPyV疾病高危的HSCT受者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46a5/8625163/9342629bbe0a/vaccines-09-01226-g001.jpg

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