Abstract: Cumulating reports suggest that acute phase proteins (APPs) have diagnostic and prognostic value in different clinical conditions. Among others, APPs are proposed to serve as markers that help to control the outcome of transplant recipients. Here, we questioned whether plasma concentrations of APPs mirror the development of chronic lung allograft dysfunction (CLAD). We performed blinded analysis of serial plasma samples retrospectively collected from 35 lung transplanted patients, of whom 25 developed CLAD and 10 remained stable during the follow-up period of 3 to 4.5 years. Albumin (ALB), alpha1-antitrypsin (AAT), high sensitivity C-reactive protein (CRPH), antithrombin-3 (AT3), ceruloplasmin (CER), and alpha2-macroglobulin (A2MG) were measured by the nephelometric method. We found that within the first six months post-transplantation, levels of A2MG, CER and AAT were higher in stable patients relative to those who later developed CLAD. Moreover, in stable patient’s plasma CRPH levels decreased during the follow-up period whereas opposite, in those developing CLAD, the CRPH gradually increased. The ALB levels became significantly lower at the end of the follow-up period in CLAD relative to a stable group. A logistic regression model based on A2MG, CER and AT3 at cut-offs levels of ≥ 175.5 mg/dL, ≥ 37.8 mg/dL and ≥ 27.35 mg/dL enabled to discriminate between stable and CLAD patients with a sensitivity of 87.5%, 100% and 62.5%, and specificity of 65.9%, 72.7% and 79.5%, respectively. We identified A2MG (below 175.5 mg/dL) as an independent predictor of CLAD (hazard ratio 11.5, 95% CI (1.5– 91.3), p< 0.021). Our findings suggest that profiles of certain APPs may help to predict the development of lung dysfunction at the very early stages after transplantation.

Keywords: acute phase proteins, transplantation, allograft dysfunction


中文翻译：

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血浆急性期蛋白作为肺移植受者中慢性肺同种异体移植功能障碍的预测因子。

摘要：越来越多的报告表明，急性期蛋白（APPs）在不同的临床条件下具有诊断和预后价值。其中，建议将APP用作帮助控制移植受体结果的标志物。在这里，我们质疑APP的血浆浓度是否反映了慢性肺同种异体移植功能障碍（CLAD）的发展。我们对从35例肺移植患者中回顾性收集的系列血浆样品进行了盲法分析，其中25例发生了CLAD，10例在3至4.5年的随访期间保持稳定。通过比浊法测量白蛋白（ALB），α1-抗胰蛋白酶（AAT），高灵敏度C反应蛋白（CRPH），抗凝血酶-3（AT3），铜蓝蛋白（CER）和α2-巨球蛋白（A2MG）。我们发现，在移植后的前六个月内，相对于后来发生CLAD的患者，稳定患者的A2MG，CER和AAT水平更高。此外，在随访期间，稳定患者的血浆CRPH水平下降，而在发展为CLAD的患者中，CRPH逐渐升高。相对于稳定组，CLAD随访期结束时ALB水平明显降低。基于A2MG，CER和AT3的logistic回归模型，其临界值≥≥175.5 mg / dL，≥37.8 mg / dL和≥27.35 mg / dL能够区分稳定患者和CLAD患者，敏感性为87.5％，100 ％和62.5％，特异性分别为65.9％，72.7％和79.5％。我们确定A2MG（低于175.5 mg / dL）是CLAD的独立预测因子（危险比11.5，95％CI（1.5-91.3），p <0.021）。

关键词：急性期蛋白移植同种异体功能障碍