Miettinen Jenni, Lautenschlager Irmeli, Weissbach Fabian, Wernli Marion, Auvinen Eeva, Mannonen Laura, Lauronen Jouni, Hirsch Hans H, Jalanko Hannu
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Pediatr Transplant. 2019 Feb;23(1):e13324. doi: 10.1111/petr.13324. Epub 2018 Nov 16.
BKPyV is an important cause of premature graft failure after KT. Most clinical studies describe BKPyV infection in adult KT patients. We studied the prevalence of post-transplant BKPyV viremia, serology, and graft function in pediatric KT recipients.
Forty-six pediatric patients transplanted between 2009 and 2014 were followed up for BKPyV DNAemia by plasma PCR for median 2.3 (range: 1-6) years. BKPyV-specific antibodies were retrospectively analyzed using virus-like particle ELISA. GFR was measured annually by Cr-EDTA clearance, and serum samples were screened for DSAs by Luminex assay.
BKPyV viremia was demonstrated in nine patients at a median of 6 months post-KT. Early BKPyV viremia at 3 months post-KT associated with decreased concomitant GFR and tendency for decreased subsequent graft function. Three of nine patients with BKPyV viremia developed DSA, all against class II antigens. PyVAN developed to four patients and responded to judicious reduction in IS. One graft was lost later due to ABMR. BKPyV-IgG was found in 18 of 31 patients (58%) tested at transplantation, and seven recipients seroconverted after transplantation with a significant increase in IgG levels with IgM. Finally, BKPyV-IgG was detectable in 31 of 40 patients (78%) at the end of the study.
Post-transplant BKPyV viremia in pediatric KT patients may alter graft function and contribute to progression of chronic allograft injury. BKPyV-IgG predicts past exposure. Low or absent BKPyV-specific antibody levels were seen pretransplant in 42% of tested patients, but were not predictive of prolonged replication or poor outcome.
BK 多瘤病毒（BKPyV）是肾移植（KT）后移植物过早失功的重要原因。大多数临床研究描述了成年 KT 患者中的 BKPyV 感染情况。我们研究了儿童 KT 受者移植后 BKPyV 病毒血症、血清学及移植物功能的流行情况。
对 2009 年至 2014 年间接受移植的 46 例儿科患者进行随访，通过血浆聚合酶链反应（PCR）检测 BKPyV 病毒血症，中位随访时间为 2.3 年（范围：1 - 6 年）。使用病毒样颗粒酶联免疫吸附测定（ELISA）对 BKPyV 特异性抗体进行回顾性分析。每年通过铬-乙二胺四乙酸（Cr-EDTA）清除率测定肾小球滤过率（GFR），并通过 Luminex检测法筛查血清样本中的供体特异性抗体（DSA）。
9 例患者在 KT 后中位 6 个月时出现 BKPyV 病毒血症。KT 后 3 个月出现的早期 BKPyV 病毒血症与同期 GFR 降低以及随后移植物功能下降趋势相关。9 例 BKPyV 病毒血症患者中有 3 例产生了 DSA，均针对Ⅱ类抗原。4 例患者发生了 BK 多瘤病毒相关肾病（PyVAN），并通过适当减少免疫抑制剂（IS）治疗有效。1 例移植物后来因抗体介导的排斥反应（ABMR）而丢失。在 31 例移植时检测的患者中有 18 例（58%）发现 BKPyV-IgG，7 例受者移植后发生血清学转换，IgG 水平显著升高伴 IgM 出现。最后，在研究结束时，40 例患者中有 31 例（78%）可检测到 BKPyV-IgG。
儿科 KT 患者移植后 BKPyV 病毒血症可能改变移植物功能，并促进慢性移植物损伤的进展。BKPyV-IgG 可预测既往感染情况。42%的检测患者移植前 BKPyV 特异性抗体水平较低或缺乏，但这并不能预测病毒的长期复制或不良预后。
