Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transplantation. 2010 Jan 15;89(1):115-23. doi: 10.1097/TP.0b013e3181bc6096.
BK virus nephropathy (BKVN) is a significant cause of renal allograft loss. Although overall intensity of immunosuppression is the greatest risk factor, recipient immune factors likely also play a role in the pathogenesis. Dendritic cells (DC) are potent antigen-presenting cells important for the induction of anti-viral cytotoxic T-cell responses. In a previous univariate analysis, we demonstrated a peripheral blood DC (PBDC) deficiency in patients with biopsy-proven BKVN, raising the possibility that reduction in DC predisposed to BK reactivation.
In this study, we refined our previous analysis by comparing random posttransplant PBDC levels between an expanded group of patients with BKVN and controls without viremia using a multivariate analysis that accounted for factors known to influence PBDC levels. Next, we compared pretransplant PBDC levels between patients stratified by the presence or absence of posttransplant viremia. Finally, we assessed the predictive value of pretransplant PBDC levels for the development of posttransplant viremia.
Analyses revealed a PBDC level deficiency not only posttransplant in patients with BKVN but also pretransplant in patients who subsequently developed posttransplant BK viremia. Furthermore, we identified a pretransplant PBDC level that is a reasonable predictor for the development of posttransplant viremia.
Our results identify PBDC deficiency as a previously unrecognized risk factor for BKV reactivation after renal transplantation. Pretransplant PBDC monitoring may prove to be a useful clinical tool in the assessment of patient vulnerability to BKVN posttransplant, which may allow more focused screening.
BK 病毒肾病(BKVN)是导致肾移植失败的重要原因。尽管免疫抑制的总体强度是最大的危险因素,但受者的免疫因素也可能在发病机制中起作用。树突状细胞(DC)是一种强大的抗原呈递细胞,对诱导抗病毒细胞毒性 T 细胞反应很重要。在之前的单变量分析中,我们发现在经活检证实的 BKVN 患者中存在外周血 DC(PBDC)缺陷,这表明 DC 的减少可能使 BK 病毒重新激活的易感性增加。
在这项研究中,我们通过使用多变量分析来比较患有 BKVN 的患者与无病毒血症的对照组之间移植后随机 PBDC 水平,对之前的分析进行了改进,该多变量分析考虑了已知影响 PBDC 水平的因素。接下来,我们比较了按移植后病毒血症的有无分层的患者的移植前 PBDC 水平。最后,我们评估了移植前 PBDC 水平对移植后病毒血症发展的预测价值。
分析显示,不仅在患有 BKVN 的患者中,而且在随后发生移植后 BK 病毒血症的患者中,移植后 PBDC 水平缺陷。此外,我们还确定了一个移植前 PBDC 水平,它是移植后病毒血症发展的合理预测指标。
我们的结果将 PBDC 缺陷确定为肾移植后 BKV 再激活的一个以前未被认识的危险因素。移植前 PBDC 监测可能成为评估患者对移植后 BKVN 易感性的有用临床工具,这可能允许更有针对性的筛查。