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移植前免疫因素可能与肾移植受者的BK多瘤病毒再激活有关。

Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients.

作者信息

DeWolfe David, Gandhi Jinal, Mackenzie Matthew R, Broge Thomas A, Bord Evelyn, Babwah Amaara, Mandelbrot Didier A, Pavlakis Martha, Cardarelli Francesca, Viscidi Raphael, Chandraker Anil, Tan Chen S

机构信息

Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.

出版信息

PLoS One. 2017 May 31;12(5):e0177339. doi: 10.1371/journal.pone.0177339. eCollection 2017.

Abstract

BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.

摘要

肾移植受者中BK多瘤病毒(BKPyV)再激活可导致移植肾损伤和丧失。对于允许再激活并负责病毒控制的适应性免疫系统要素,目前仍未完全阐明。我们进行了一项前瞻性研究,评估了两个中心28例患者从移植前到移植后一年的BKPyV特异性T细胞反应、体液反应和总体T细胞表型。我们对病毒血症和病毒尿发生的危险因素进行了探索性分析,并比较了这些组与BK阴性患者对BKPyV的免疫反应。6例患者出现病毒尿,3例出现病毒血症。BKPyV特异性CD8+T细胞在病毒血症和病毒尿患者移植后增加,但在BK阴性患者中未增加。BKPyV特异性CD4+T细胞在病毒血症患者中增加,但在病毒尿或BK阴性患者中未增加。抗BKPyV IgG抗体在病毒尿和病毒血症患者中增加,但在BK阴性患者中保持不变。病毒血症患者在移植前和移植后12个月时CD8+效应细胞比例更高。病毒血症患者在移植后3个月时CD4+效应记忆细胞较少。探索性分析表明,较低的CD4比例、较高的总CD8比例、较高的抗BKPyV抗体滴度以及肾衰竭病因与BKPyV再激活相关。总之,在出现病毒血症的患者移植前发现低CD4、高CD8和效应CD8细胞增加,这是一种与免疫衰老相关的表型。这种移植前T细胞衰老表型可能有助于识别BKPyV再激活风险增加的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d6/5451008/d60193d1b837/pone.0177339.g001.jpg

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