Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Hirakara, Japan.
Am J Transplant. 2014 Jun;14(6):1425-32. doi: 10.1111/ajt.12718. Epub 2014 May 1.
The long-term success of lung transplantation is limited by chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the alveolar alarmin profiles in CLAD subtypes, restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). Bronchoalveolar lavage (BAL) samples were collected from 53 recipients who underwent double lung or heart-lung transplantation, including patients with RAS (n = 10), BOS (n = 18) and No CLAD (n = 25). Protein levels of alarmins such as S100A8, S100A9, S100A8/A9, S100A12, S100P, high-mobility group box 1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in BAL fluid were measured. RAS and BOS showed higher expressions of S100A8, S100A8/A9 and S100A12 compared with No CLAD (p < 0.0001, p < 0.0001, p < 0.0001 in RAS vs. No CLAD, p = 0.0006, p = 0.0044, p = 0.0086 in BOS vs. No CLAD, respectively). Moreover, RAS showed greater up-regulation of S100A9, S100A8/A9, S100A12, S100P and HMGB1 compared with BOS (p = 0.0094, p = 0.038, p = 0.041, p = 0.035 and p = 0.010, respectively). sRAGE did not show significant difference among the three groups (p = 0.174). Our results demonstrate distinct expression patterns of alveolar alarmins in RAS and BOS, suggesting that RAS and BOS may represent biologically different subtypes. Further refinements in biologic profiling will lead to a better understanding of CLAD.
肺移植的长期成功受到慢性肺移植物功能障碍（CLAD）的限制。本研究旨在探讨 CLAD 亚型（限制性移植物综合征（RAS）和闭塞性细支气管炎综合征（BOS））中肺泡警报素谱。对 53 名接受双肺或心肺移植的受者的支气管肺泡灌洗液（BAL）样本进行了收集，其中包括 RAS 患者（n=10）、BOS 患者（n=18）和无 CLAD 患者（n=25）。测量 BAL 液中警报素（S100A8、S100A9、S100A8/A9、S100A12、S100P、高迁移率族蛋白 1（HMGB1）和可溶性晚期糖基化终产物受体（sRAGE））的蛋白水平。与无 CLAD 患者相比，RAS 和 BOS 患者的 S100A8、S100A8/A9 和 S100A12 表达更高（RAS 与无 CLAD 患者相比，p＜0.0001、p＜0.0001、p＜0.0001；BOS 与无 CLAD 患者相比，p=0.0006、p=0.0044、p=0.0086）。此外，与 BOS 相比，RAS 患者的 S100A9、S100A8/A9、S100A12、S100P 和 HMGB1 表达更高（p=0.0094、p=0.038、p=0.041、p=0.035、p=0.010）。三组间 sRAGE 无显著差异（p=0.174）。我们的结果表明，RAS 和 BOS 中肺泡警报素的表达模式不同，提示 RAS 和 BOS 可能代表生物学上不同的亚型。进一步的生物学特征分析将有助于更好地理解 CLAD。
