Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Department of Pediatrics II, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Transplantation. 2020 Nov;104(11):2393-2402. doi: 10.1097/TP.0000000000003133.
After kidney transplantation, uncontrolled BK polyomavirus (BKPyV) replication causes kidney graft failure through BKPyV-associated nephropathy (BKPyVAN), but markers predicting outcome are missing. BKPyV-specific T cells may serve as a predictive marker to identify patients at risk of persistent DNAemia and BKPyVAN.
Out of a total of 114 pediatric kidney recipients transplanted between 2008 and 2018, 36 children with posttransplant BKPyV-DNAemia were identified. In a prospective noninterventional study, BKPyV-specific CD4 and CD8 T cells were measured in 32 of 36 viremic pediatric kidney recipients using intracellular cytokine staining and flow cytometry. The course of the BKPyV replication was monitored with regard to duration of BKPyV-DNAemia and need of therapeutic intervention and diagnosis of proven BKPyVAN.
Levels of BKPyV-specific T cells negatively correlated with subsequent duration of BKPyV-DNAemia. Patients with BKPyV-specific CD4 T cells ≥0.5 cells/µL and/or BKPyV-specific CD8 T cells ≥0.1 cells/µL had transient, self-limiting DNAemia (PPV 1.0, NPV 0.86). BKPyV-specific CD4 and CD8 T cells below these thresholds were found in children with persistent BKPyV-DNAemia and biopsy-proven BKPyVAN with need for therapeutic intervention. After reducing immunosuppressive therapy, levels of BKPyV-specific CD4 T cells increased while plasma BKPyV-DNAemia declined.
This study found that BKPyV-specific T cell levels may help to distinguish patients with transient, self-limiting BKPyV-DNAemia from those with persisting BKPyV-DNAemia and biopsy-proven BKPyVAN, who would benefit from individualized therapeutic interventions such as reduced immunosuppression. Thereby the risk for rejection because of unnecessary reduction of immunosuppression in case of self-limiting BKPyV-DNAemia can be minimized.
肾移植后，由于 BK 多瘤病毒（BKPyV）不受控制的复制，导致 BKPyV 相关性肾病（BKPyVAN）而使移植肾失功，但目前缺乏预测结局的标志物。BKPyV 特异性 T 细胞可能作为一种预测标志物，用于识别存在持续 DNA 血症和 BKPyVAN 风险的患者。
总共纳入了 2008 年至 2018 年间进行肾移植的 114 例儿科患者，其中 36 例患者发生了移植后 BKPyV-DNA 血症。在一项前瞻性非干预性研究中，通过细胞内细胞因子染色和流式细胞术，检测了 32 例病毒血症的儿科肾移植受者的 BKPyV 特异性 CD4 和 CD8 T 细胞。监测 BKPyV 复制的过程，包括 BKPyV-DNA 血症的持续时间、治疗干预的需要以及 BKPyVAN 的确诊。
BKPyV 特异性 T 细胞水平与随后的 BKPyV-DNA 血症持续时间呈负相关。BKPyV 特异性 CD4 T 细胞≥0.5 个/μL 和/或 BKPyV 特异性 CD8 T 细胞≥0.1 个/μL 的患者具有短暂、自限性的 DNA 血症（PPV 1.0，NPV 0.86）。在持续性 BKPyV-DNA 血症和需要治疗干预的活检证实的 BKPyVAN 患者中，发现了低于这些阈值的 BKPyV 特异性 CD4 和 CD8 T 细胞。在减少免疫抑制治疗后，BKPyV 特异性 CD4 T 细胞水平增加，而血浆 BKPyV-DNA 血症下降。
本研究发现，BKPyV 特异性 T 细胞水平有助于区分具有短暂、自限性 BKPyV-DNA 血症的患者与持续性 BKPyV-DNA 血症和活检证实的 BKPyVAN 患者，这些患者需要个体化的治疗干预，如减少免疫抑制。因此，可以将因不必要地减少自限性 BKPyV-DNA 血症患者的免疫抑制而导致排斥反应的风险降到最低。
