Patel Jawaharlal M, Hu Hanbo, Lu Li, Deem Amy, Akindipe Olufemi, Brantly Mark, Block Edward R, Antony Veena B, Baz Maher A
Division of Pulmonary Critical Care, and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, FL 32610-0225, USA.
Biomarkers. 2008 Aug;13(5):486-95. doi: 10.1080/13547500802061822.
Primary graft dysfunction and rejection are common complications in lung transplant recipients. Increased expression of thioredoxin-1 (Trx), a 12-kDa redox-regulatory protein, has been reported in multiple lung pathophysiological conditions involving oxidative and inflammatory mediated injury including graft rejection in canine and rat models of lung transplantation. Our objective was to determine whether increased Trx expression is associated with progression of rejection pathophysiology in human lung transplant recipients. Bronchoalveolar lavage (BAL) fluid and transbronchial biopsy samples were collected as a routine part of post-transplant clinical care from 18 lung transplant patients from our adult lung transplant programme. Lung transplant recipient profile included age/sex, ethnic background, days on ventilator, total ischaemic time, and cytomegalovirus (CMV) status. Based on histopathological grading criteria, patients were divided into two groups, rejecting (A1/A2 or B1) and non-rejecting (A0/B0). Rejecting and non-rejecting group total BAL cell counts and differential cell counts for neutrophils, macrophages, lymphocytes and eosinophils as well as total BAL cell Trx levels were analysed. Total BAL cell counts were significantly (p <0.05) elevated in graft rejecting versus non-rejecting patients. Differential BAL macrophage counts were comparable in rejection and non-rejection groups, whereas there were significant increases in neutrophils and lymphocytes but not eosinophils in patients with rejection versus non-rejection pathology (p <0.05). Total ischaemic time and days on ventilator in rejection and non-rejection groups were comparable. However, Trx levels were significantly elevated in BAL cells from graft-rejecting patients compared with non-rejecting patients (p <0.05). These data suggest that surveillance monitoring of BAL Trx levels after lung transplantation can serve as a biomarker to assess severity of graft rejection.
原发性移植肺功能障碍和排斥反应是肺移植受者常见的并发症。硫氧还蛋白-1（Trx）是一种12 kDa的氧化还原调节蛋白，在多种肺部病理生理状况下，包括在犬和大鼠肺移植模型中的移植排斥反应等涉及氧化和炎症介导损伤的情况下，其表达均有增加。我们的目的是确定Trx表达增加是否与人类肺移植受者排斥反应病理生理的进展相关。作为我们成人肺移植项目中移植后临床护理的常规部分，收集了18例肺移植患者的支气管肺泡灌洗（BAL）液和经支气管活检样本。肺移植受者的资料包括年龄/性别、种族背景、呼吸机使用天数、总缺血时间和巨细胞病毒（CMV）状态。根据组织病理学分级标准，将患者分为两组，即排斥组（A1/A2或B1）和非排斥组（A0/B0）。分析了排斥组和非排斥组的BAL细胞总数以及中性粒细胞、巨噬细胞、淋巴细胞和嗜酸性粒细胞的分类细胞计数，以及BAL细胞Trx总水平。与非排斥患者相比，移植排斥患者的BAL细胞总数显著升高（p<0.05）。排斥组和非排斥组的BAL巨噬细胞分类计数相当，而与非排斥病理的患者相比，排斥患者的中性粒细胞和淋巴细胞显著增加，但嗜酸性粒细胞没有增加（p<0.05）。排斥组和非排斥组的总缺血时间和呼吸机使用天数相当。然而，与非排斥患者相比，移植排斥患者的BAL细胞中Trx水平显著升高（p<0.05）。这些数据表明，肺移植后监测BAL Trx水平可作为评估移植排斥严重程度的生物标志物。
