Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease
Loss of endothelial thrombomodulin predicts response to steroid therapy and survival in acute intestinal graft-versus-host disease
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DOI：
10.3324/haematol.2011.061051
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发表时间：
2012-11-01
期刊：
影响因子：
--
通讯作者：
Luft, Thomas
中科院分区：
文献类型：
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作者：
Andrulis, Mindaugas;Dietrich, Sascha;Luft, Thomas
类固醇难治性移植物抗宿主病导致异基因干细胞移植后显著的发病率和死亡率。目前尚不清楚类固醇耐药性的病理机制，但有人认为内皮细胞功能障碍发挥了作用。在51例同种异体移植患者的结肠活检中，内皮血栓调节蛋白与上皮损伤和细胞毒性T细胞的组织学标志物一起进行了沿着定量，并回顾性地与对类固醇的反应和存活率相关。在校正T细胞浸润、组织学分级、血管密度、疾病状态、供体类型和预处理治疗的多变量分析中，内皮血栓调节蛋白的缺失是对类固醇反应（P=0.02）和非复发死亡率（P=0.01）的最强预测因子。我们的数据提供的证据表明，在疾病发作时，内皮血栓调节蛋白表达的损失，而不是过度的T细胞浸润与类固醇难治性移植物抗宿主病和死亡率。现在有必要进行前瞻性的组织学研究，以提高对干细胞移植这一核心并发症的诊断和鉴别。
Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in colon biopsies from 51 allografted patients, and retrospectively correlated with response to steroids and survival. Loss of endothelial thrombomodulin was the strongest predictor of response to steroids (P=0.02) and non-relapse mortality (P=0.01) in multivariate analyses adjusting for T-cell infiltrates, histological grading, vessel density, disease status, donor type, and conditioning therapy. Our data provide evidence that at disease onset, loss of endothelial thrombomodulin expression rather than excessive T-cell infiltration associates with steroid-refractory graft-versus-host disease and mortality. Prospective histological investigations are now warranted to improve diagnosis and prognostication of this core complication of stem cell transplantation.