Epithelial cell death markers in bronchoalveolar lavage correlate with chronic lung allograft dysfunction subtypes and survival in lung transplant recipients-a single-center retrospective cohort study
Epithelial cell death markers in bronchoalveolar lavage correlate with chronic lung allograft dysfunction subtypes and survival in lung transplant recipients-a single-center retrospective cohort study
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DOI：
10.1111/tri.13444
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发表时间：
2019-09-01
影响因子：
3.1
通讯作者：
Martinu, Tereza
中科院分区：
文献类型：
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作者：
Levy, Liran;Tigert, Alexander;Martinu, Tereza
慢性肺移植物功能障碍（CLAD）仍然是肺移植术后晚期死亡的主要原因。上皮损伤被认为是CLAD发病机制中的关键事件。M30和M65分别是上皮细胞凋亡和总细胞死亡期间特异性释放的细胞角蛋白-18片段。我们研究了支气管肺泡灌洗（BAL）中M30和M65水平是否与CLAD亚型相关：限制性同种异体移植综合征（RAS）与闭塞性细支气管炎综合征（BOS）。巴尔斯来自26例确诊CLAD患者（10例RAS，16例BOS）和19例长期无CLAD对照。排除合并感染或急性排斥反应的样本。通过ELISA测量蛋白质水平。使用Kruskal-Wallis、Mann-Whitney U检验和卡方检验比较变量。使用考克斯PH模型评估M30和M65水平与CLAD后存活率的关联。RAS中M65水平显著高于BOS和长期无CLAD对照组，并与CLAD后生存率较差相关。RAS患者肺上皮细胞死亡增加。BAL M65的检测可用于区分CLAD亚型，并作为确诊CLAD患者的预后标志物。了解上皮细胞死亡在CLAD发病机制中的作用可能有助于确定新的治疗靶点以改善结果。
Chronic lung allograft dysfunction (CLAD) remains the leading cause of late death after lung transplantation. Epithelial injury is thought to be a key event in the pathogenesis of CLAD. M30 and M65 are fragments of cytokeratin-18 released specifically during epithelial cell apoptosis and total cell death, respectively. We investigated whether M30 and M65 levels in bronchoalveolar lavage (BAL) correlate with CLAD subtypes: restrictive allograft syndrome (RAS) versus bronchiolitis obliterans syndrome (BOS). BALs were obtained from 26 patients with established CLAD (10 RAS, 16 BOS) and 19 long-term CLAD-free controls. Samples with concurrent infection or acute rejection were excluded. Protein levels were measured by ELISA. Variables were compared using Kruskal-Wallis, Mann-Whitney U test and Chi-squared tests. Association of M30 and M65 levels with post-CLAD survival was assessed using a Cox PH models. M65 levels were significantly higher in RAS compared to BOS and long-term CLAD-free controls and correlated with worse post-CLAD survival. Lung epithelial cell death is enhanced in patients with RAS. Detection of BAL M65 may be used to differentiate CLAD subtypes and as a prognostic marker in patients with established CLAD. Understanding the role of epithelial cell death in CLAD pathogenesis may help identify new therapeutic targets to improve outcome.