Endothelial Vulnerability and Endothelial Damage Are Associated with Risk of Graft-versus-Host Disease and Response to Steroid Treatment
Endothelial Vulnerability and Endothelial Damage Are Associated with Risk of Graft-versus-Host Disease and Response to Steroid Treatment
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DOI：
10.1016/j.bbmt.2012.09.018
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发表时间：
2013-01-01
影响因子：
4.3
通讯作者：
Luft, Thomas
中科院分区：
文献类型：
--
作者：
Dietrich, Sascha;Falk, Christine S.;Luft, Thomas
越来越多的证据表明内皮细胞因子参与了GVHD的发病机制。我们最近表明，类固醇难治性，但不敏感，GVHD的特点是较高的移植前血清血管生成素-2（ANG 2），一种激素介导的内皮脆弱性。为了评估内皮脆弱性是否是GVHD本身的危险因素或仅在明显的GVHD建立时才变得重要，我们测量了ANG 2沿着额外的内皮应激血清标志物，包括可溶性血栓调节蛋白（sTM），IL-8（OCCL 8）和肝细胞生长因子（HGF），在没有，低度或重度GVHD的患者中。难治性GVHD患者移植后血清ANG 2、sTM、HGF和IL-8水平高于敏感性GVHD患者和非GVHD患者。移植前ANG 2是唯一与难治性和死亡风险相关的生长因子，并且仅在发生III-IV级GVHD的患者亚组中。相反，ANG 2不能预测无GVHD或低级别GVHD患者的GVHD或非复发死亡率（NRM）。这些发现提供了证据表明，内皮功能发挥了重要作用的类固醇难治性的发病机制，在进行性GVHD，但是，内皮细胞的脆弱性并不能预测GVHD的发病率。(C)2013年美国血液和骨髓移植协会。
There is accumulating evidence indicating that endothelial factors are involved in the pathogenesis of GVHD. We have recently shown that steroid-refractory, but not sensitive, GVHD is characterized by higher pre-transplantation serum levels of angiopoetin-2 (ANG2), a hormone mediating endothelial vulnerability. To evaluate whether endothelial vulnerability is a risk factor for GVHD per se or becomes important only when noticeable GVHD is established, we measured ANG2 along with additional serum markers of endothelial stress, including soluble thrombomodulin (sTM), IL-8 (OCCL8), and hepatocyte growth factor (HGF), in patients with no, low-grade, or severe GVHD. Patients with refractory GVHD exhibited elevated serum levels of ANG2, sTM, HGF, and IL-8 posttransplantation compared with patients with sensitive GVHD and patients without GVHD. Pretransplantation ANG2 was the only growth factor correlated with the risk of refractoriness and mortality, and then only within the subset of patients who developed grade III-IV GVHD. In contrast, ANG2 was not predictive of GVHD or nonrelapse mortality (NRM) in patients with no GVHD or low-grade GVHD. These findings provide evidence that endothelial function plays an important role in the pathogenesis of steroid refractoriness in ongoing GVHD; however, endothelial vulnerability does not predict incidence of GVHD. (C) 2013 American Society for Blood and Marrow Transplantation.