Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation.
Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation.
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接受肝移植的患者中与早期同种异体功能障碍相关的血清细胞因子谱。
DOI：
10.1002/lt.22451
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发表时间：
2012-02
影响因子：
4.6
通讯作者：
Olthoff, Kim M.
中科院分区：
文献类型：
--
作者：
Friedman, Benjamin H.;Wolf, Joshua H.;Wang, Liqing;Putt, Mary E.;Shaked, Abraham;Christie, Jason D.;Hancock, Wayne W.;Olthoff, Kim M.
肝移植术后第一周发生的早期同种异体移植物功能障碍（EAD）与移植物衰竭和死亡率增加有关，并且被认为主要是由于缺血/再灌注损伤。我们预期EAD的存在将通过与围手术期炎症反应相关的血清蛋白表达的改变来反映，并假设特定的表达模式可能与EAD的发展相关。采用Luminex多重检测法测定肝移植前后25种细胞因子、趋化因子和免疫受体的血清水平。使用术前和移植后1、7、14和30天收集的样本，在连续时间点比较有或无EAD的成年受者中每种细胞因子生物标志物的水平。根据标准标准将EAD定义为第1-7天最大丙氨酸转移酶（ALT）或天冬氨酸转移酶（AST）水平>2000 U/ml，第7天胆红素水平≥10 mg/dl，或第7天国际标准化比值（INR）≥1.7。多变量分析显示，EAD患者术前IL-6水平较低，IL-2 R水平较高。EAD患者在术后早期也显示出较高的MCP-1（CCL 2）、IL-8（CXCL 8）和RANTES（CCL 5）趋化因子水平，表明NF-κB通路上调，此外还显示出较高水平的趋化因子和与T细胞免疫相关的细胞因子，包括Mig（CXCL 9）、IP-10（CXCL 10）和IL-2 R。这些发现确定了与EAD相关的几种可能的生物标志物和途径，这可能指导未来的验证研究和移植物功能障碍的特定细胞和分子机制的调查。此外，如果得到验证，我们的研究结果可能有助于围手术期预测EAD的发生，并最终导致潜在的介入治疗的识别。
Early allograft dysfunction (EAD) occurring in the first week post-liver transplantation is associated with increased graft failure and mortality and is believed to be largely due to ischemia/reperfusion injury. We anticipated that the presence of EAD would be reflected by alterations in expression of serum proteins associated with an inflammatory response in the peri-operative period, and hypothesized that a specific pattern of expression might correlate with the development of EAD. The serum levels of 25 cytokines, chemokines, and immunoreceptors were measured by Luminex multiplex assays pre- and post-liver transplantation. Levels of each cytokine biomarker were compared in adult recipients with or without EAD at serial time points using samples collected pre-operatively and at 1, 7, 14, and 30 days post-transplant. EAD was defined according to standard criteria as maximum alanine transferase (ALT) or aspartate transferase (AST) levels on days 1–7 of >2000 U/ml, day 7 bilirubin level ≥10 mg/dl, or a day 7 international normalized ratio (INR) ≥1.7. Multivariable analyses showed that patients experiencing EAD had lower pre-operative IL-6 and higher IL-2R levels. Patients with EAD also showed higher MCP-1 (CCL2), IL-8 (CXCL8), and RANTES (CCL5) chemokine levels in the early post-operative period, suggesting up-regulation of the NF-κB pathway, in addition to higher levels of chemokines and cytokines associated with T cell immunity, including Mig (CXCL9), IP-10 (CXCL10) and IL-2R. These findings identify several possible biomarkers and pathways associated with EAD, that may guide future validation studies and investigation of specific cellular and molecular mechanisms of graft dysfunction. Furthermore, if validated, our findings may contribute to perioperative prediction of the occurrence of EAD and ultimately lead to identification of potential interventional therapies.
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影响因子：
6.2
作者：
Xie, Jin-Fu;Wang, Guodong;Olthoff, Kim M.
通讯作者：
Olthoff, Kim M.
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0.9
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Ferron, J. A.
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6.2
作者：
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通讯作者：
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