Institute of Pathology, University Hospital Heidelberg, Freiburg, Germany.
Haematologica. 2012 Nov;97(11):1674-7. doi: 10.3324/haematol.2011.061051. Epub 2012 Jun 11.
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 nonrelapse 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.
激素难治性移植物抗宿主病（GVHD）是异基因造血干细胞移植后导致发病率和死亡率显著增加的主要原因。目前尚不清楚激素抵抗的发病机制，但有研究表明内皮细胞功能障碍可能发挥了作用。本研究通过对 51 例异基因移植患者的结肠活检组织进行分析，检测了组织学上皮损伤和细胞毒性 T 细胞的同时，还定量分析了内皮血栓调节蛋白，并回顾性分析了其与激素反应和生存之间的关系。多变量分析调整 T 细胞浸润、组织学分级、血管密度、疾病状态、供者类型和预处理治疗后，内皮血栓调节蛋白丢失是激素反应（P=0.02）和非复发死亡率（P=0.01）的最强预测因子。我们的数据提供了证据表明，在疾病发作时，内皮血栓调节蛋白表达缺失而不是过度的 T 细胞浸润与激素难治性移植物抗宿主病和死亡率相关。现在需要进行前瞻性的组织学研究，以改善对干细胞移植这一核心并发症的诊断和预后判断。
