Meloni Federica, Salvini Roberta, Bardoni Anna Maria, Passadore Ileana, Solari Nadia, Vitulo Patrizio, Oggionni Tiberio, Viganò Mario, Pozzi Ernesto, Fietta Anna Maria
Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia, Pavia, Italy.
J Heart Lung Transplant. 2007 Nov;26(11):1135-43. doi: 10.1016/j.healun.2007.08.009.
Bronchiolitis obliterans syndrome (BOS) affects long-term survival of lung transplant (Tx) recipients (LTRs), with no consistently effective treatment strategy. Identifying early markers of BOS is of paramount importance for improving graft survival.
We used 2-dimensional gel electrophoresis and protein identification by mass spectrometry to compare the protein profile of bronchoalveolar lavage fluid (BALf) in two groups of LTRs: one composed of patients with BOS and the other composed of patients with good graft function at >5 years post-surgery (stable LTRs). Based on the hypothesis that only proteins of lung origin could represent reliable BOS markers, we also evaluated paired plasma samples. Proteins of interest were also assessed in the BALf of control subjects and results confirmed by dot- blot analysis.
Among 11 differentially expressed proteins, we identified 2 locally produced factors: peroxiredoxin II (PRXII), exclusively expressed in BOS; and surfactant protein A (SP-A), expressed consistently less in BOS patients than in stable LTRs. PRXII expression was never observed in BALf from control subjects, whereas SP-A was present in higher amounts compared with stable LTRs and BOS patients. Finally, the time course of SP-A was studied in 5 LTRs who subsequently developed BOS. A reduction in BALf SP-A content was detectable early after Tx, preceding BOS onset in 4 of 5 patients.
Our results suggest that testing SP-A levels in BALf could predict LTR patients who are at higher risk of BOS development.
闭塞性细支气管炎综合征（BOS）影响肺移植（Tx）受者（LTRs）的长期生存，且尚无一致有效的治疗策略。识别BOS的早期标志物对于提高移植物存活率至关重要。
我们使用二维凝胶电泳和质谱蛋白质鉴定技术，比较两组LTRs支气管肺泡灌洗液（BALf）的蛋白质谱：一组由BOS患者组成，另一组由术后5年以上移植物功能良好的患者（稳定LTRs）组成。基于只有肺源性蛋白质才能代表可靠的BOS标志物这一假设，我们还评估了配对的血浆样本。在对照受试者的BALf中也对感兴趣的蛋白质进行了评估，并通过斑点印迹分析证实了结果。
在11种差异表达的蛋白质中，我们鉴定出2种局部产生的因子：过氧化物酶体增殖物激活受体γ配体2（PRXII），仅在BOS中表达；以及表面活性蛋白A（SP-A），在BOS患者中的表达始终低于稳定LTRs。对照受试者的BALf中从未观察到PRXII的表达，而与稳定LTRs和BOS患者相比，SP-A的含量更高。最后，在5名随后发生BOS的LTRs中研究了SP-A的时间进程。在Tx后早期可检测到BALf中SP-A含量的降低，5名患者中有4名在BOS发作之前出现。
我们的结果表明，检测BALf中的SP-A水平可以预测LTR患者发生BOS的风险较高。
