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Associations between acute GVHD-related biomarkers and endothelial cell activation after allogeneic hematopoietic stem cell transplantation

机译:同种异体造血干细胞移植术后急性GVHD相关生物标志物与内皮细胞活化的缔合

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Abstract Background Hematopoietic stem cell transplantation (HSCT) can cause serious transplant-related complications such as graft-versus-host disease (GVHD). Acute GVHD (aGVHD) has been diagnosed by clinical manifestations, laboratory data and pathological effects until now, but recently the discovery of specific biomarkers such as suppression of tumorigenicity 2 (ST2), elafin and regenerating islet-derived 3α (REG3α) is challenging this approach. Methods We investigated the expression of aGVHD-related markers (regulated on activation normal T-cell expressed and secretes: RANTES, elafin, REG3α and ST2) and endothelial cell activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT. Additionally, we studied the effects of recombinant soluble thrombomodulin (rTM) on the expression of these markers. Our study cohort included 225 patients who underwent allogeneic HSCT at several institutions in Japan. Results RANTES, sVCAM-1, PAI-1, elafin, REG3α and ST2 exhibited significant increases in patients not receiving rTM after HSCT. When we examined patients with confirmed complications, the frequencies of aGVHD and VOD were significantly lower in the rTM-treated group. In addition, aGVHD-related biomarkers such as elafin, REG3α, and ST2 were elevated significantly in patients with aGVHD. Conclusion Our findings suggest that endothelial cell activation might be linked to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its effect on endothelial cells.
机译:摘要背景造血干细胞移植(HSCT)可导致严重的移植相关并发症,如移植物抗宿主病(GVHD)。到目前为止,急性GVHD(aGVHD)已经通过临床表现、实验室数据和病理效应进行诊断,但最近发现的特异性生物标记物,如抑瘤性2(ST2)、elafin和再生胰岛衍生的3α(REG3α),对这种方法提出了挑战。方法我们研究了aGVHD相关标记物(受活化调节的正常T细胞表达和分泌:RANTES、elafin、REG3α和ST2)和内皮细胞活化标记物(可溶性血管细胞粘附分子:sVCAM-1和纤溶酶原激活物抑制剂:PAI-1)在接受异基因HSCT患者中的表达。此外,我们还研究了重组可溶性血栓调节蛋白(rTM)对这些标记物表达的影响。我们的研究队列包括225名在日本多家机构接受同种异体HSCT的患者。结果HSCT术后未接受rTM治疗的患者RANTES、sVCAM-1、PAI-1、elafin、REG3α和ST2显著升高。当我们检查有确诊并发症的患者时,rTM治疗组的aGVHD和VOD发生率显著降低。此外,aGVHD患者的aGVHD相关生物标志物如elafin、REG3α和ST2显著升高。结论我们的研究结果表明,内皮细胞活化可能与aGVHD有关,rTM可能通过对内皮细胞的作用,至少部分地起到预防aGVHD的作用。

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