Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients.
Pre-transplant immune factors may be associated with BK polyomavirus reactivation in kidney transplant recipients.
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DOI：
10.1371/journal.pone.0177339
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tan CS
中科院分区：
文献类型：
--
作者：
DeWolfe D;Gandhi J;Mackenzie MR;Broge TA Jr;Bord E;Babwah A;Mandelbrot DA;Pavlakis M;Cardarelli F;Viscidi R;Chandraker A;Tan CS
BK 多瘤病毒 (BKPyV) 在肾移植受者中重新激活可导致同种异体移植物损伤和丢失。适应性免疫系统中允许重新激活并负责病毒控制的要素仍未完全描述。我们对两个中心的 28 名患者进行了一项前瞻性研究，评估从移植前开始到移植后一年的 BKPyV 特异性 T 细胞反应、体液反应和总体 T 细胞表型。我们对发生病毒血症和病毒尿的危险因素进行了探索性分析，并比较了这些群体和 BK 阴性群体对 BKPyV 的免疫反应。 6 名患者出现病毒尿症，3 名患者出现病毒血症。在病毒血症和病毒感染患者中，BKPyV 特异性 CD8+ T 细胞在移植后增加，但 BK 阴性患者则没有增加。 BKPyV 特异性 CD4+ T 细胞在病毒血症患者中增加，但病毒血症或 BK 阴性患者中不增加。病毒性和病毒血症患者的抗 BKPyV IgG 抗体增加，但 BK 阴性患者的抗 BKPyV IgG 抗体保持不变。病毒血症患者在移植前和移植后 12 个月时具有较高比例的 CD8+ 效应细胞。移植后 3 个月，病毒血症患者的 CD4+ 效应记忆细胞较少。探索性分析表明，较低的 CD4 和较高的总 CD8 比例、较高的抗 BKPyV 抗体滴度以及肾衰竭的原因与 BKPyV 重新激活相关。总之，在出现病毒血症（一种与免疫衰老相关的表型）的患者中，在移植前发现了低 CD4、高 CD8 和增加的效应 CD8 细胞。这种移植前 T 细胞衰老表型有可能用于识别 BKPyV 重新激活风险增加的患者。
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.