Elevated myeloid: plasmacytoid dendritic cell ratio associates with late, but not early, liver rejection in children induced with rabbit anti-human thymocyte globulin.
Elevated myeloid: plasmacytoid dendritic cell ratio associates with late, but not early, liver rejection in children induced with rabbit anti-human thymocyte globulin.
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DOI：
10.1097/tp.0b013e3181b11f12
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发表时间：
2009-08-27
期刊：
影响因子：
6.2
通讯作者：
Sindhi R
中科院分区：
文献类型：
--
作者：
Gupta A;Kumar CA;Ningappa M;Sun Q;Higgs BW;Snyder S;Zeevi A;Thomson AW;Mazariegos GV;Sindhi R
树突状细胞（DC）在免疫反应的诱导和调节中发挥着重要作用。通过流式细胞术分析，对 48 名儿童进行一次横断面分析，并对 30 名肝移植 (LTx) 后的儿童进行纵向分析（移植前，以及移植后第 1-60、61-200、201-400 天）。所有儿童均接受 53/25 尸体/活体供体同种异体肝脏移植，并进行兔抗人胸腺细胞球蛋白 (rATG) 诱导和无类固醇他克莫司治疗。两组中的排斥者都是那些在 DC 监测的 60 天内经历了经活检证实的急性细胞排斥 (ACR) 的儿童 (n=35)。在纵向和横向队列的排斥者中，MDC：PDC 比率较高，并且与 PDC 频率降低相关。对 30 名横截面受试者进行的 Logistic 回归分析、留一法交叉验证和接受者操作特征分析显示，MDC:PDC 比率 1.78 与排斥状态相关，敏感性/特异性为 76.9/88.2%。在 LTx 后的早期 60 天期间，敏感性和特异性在其余 18 名横断面受试者中得到了重复（分别为 88.8% 和 78.8%），但在纵向监测受试者中没有得到重复（分别为 30.76 % 和 62.50%）。在 48 名横截面受试者中观察到他克莫司全血浓度与 PDC 频率之间存在显着负相关（Spearman r = -0.370，p = 0.005），这些受试者在 LTx 后 1-3 年监测 DC 亚群，但不在 LTx 后早期监测。我们得出的结论是，MDC：PDC 比率升高与肝移植排斥相关，这种情况发生在用 rATG 诱导的儿童一年后。
Dendritic cells (DC) play an important role in the induction and regulation of immune responses. Myeloid CD11c+DC (MDC), which may have inflammatory functions, and plasmacytoid CD123+ DC (PDC), which may have tolerogenic potential, were measured by flow cytometric analysis, cross-sectionally, once, in 48 children, and longitudinally (pre-transplant, and at days 1–60, 61–200, 201–400 post transplant) in 30 children following liver transplantation (LTx). All children received 53/25 cadaveric/live donor liver allografts with rabbit anti-human thymocyte globulin (rATG) induction, and steroid-free Tacrolimus therapy. Rejectors in both groups were those children (n=35), who experienced biopsy-proven acute cellular rejection (ACR) within 60 days of DC monitoring. Among rejectors in the longitudinal and cross-sectional cohorts, the MDC: PDC ratio was higher, and was associated with decreased PDC frequencies. Logistic regression analysis, leave-one out cross-validation, and receiver operating characteristic analysis applied to 30 cross-sectional subjects revealed that an MDC:PDC ratio 1.78 was associated with rejector status with sensitivity/specificity of 76.9/88.2%. Sensitivity and specificity were replicated in the 18 remaining cross-sectional subjects (88.8 and 78.8%, respectively), but not in longitudinally-monitored subjects, during the early, 60-day period after LTx (30.76 and 62.50%, respectively). A significant negative correlation was observed between Tacrolimus whole blood concentrations and PDC frequencies (Spearman r = −0.370, p=0.005) in 48 cross-sectional subjects in whom DC subsets were monitored 1–3 years after LTx, but not during the early post-LTx period. We conclude that an elevated MDC: PDC ratio associates with liver graft rejection, which occurs after first year in children induced with rATG.