Kriegova Eva, Melle Christian, Kolek Vitezslav, Hutyrova Beata, Mrazek Frantisek, Bleul Annett, du Bois Roland M, von Eggeling Ferdinand, Petrek Martin
Palacky University, Medical Faculty, I.P. Pavlova Str. 6, CZ-775 20 Olomouc, Czech Republic.
Am J Respir Crit Care Med. 2006 May 15;173(10):1145-54. doi: 10.1164/rccm.200507-1126OC. Epub 2006 Jan 26.
Pulmonary sarcoidosis is a multisystem granulomatous disease with various clinical phenotypes. So far, there has been little information on protein patterns (PPs) of bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis and no data are available on PPs in clinical disease subtypes.
To investigate the PP of BALF from patients with pulmonary sarcoidosis, to evaluate whether PPs reflect disease course as assessed by chest X-ray (CXR), and to compare PPs between patients with/without Löfgren's syndrome.
Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy was applied to investigate PPs in unconcentrated BALF from 65 patients (CXR stage I, n = 32; CXR stage II, n = 22, CXR stage III, n = 11) and 23 healthy control subjects. The Mann-Whitney U test was used to detect differentially expressed protein peaks. After reversed-phase fractionation, peptide fingerprint mapping and immunodepletion were used to identify deregulated (up-regulated or down-regulated) proteins.
Forty differentially expressed protein entities (2.75-185.62 kD) were detected in patients with pulmonary sarcoidosis versus control subjects (p < 0.05). Whereas 13 peaks (33%) were present across all CXR stages, 27 (67%) were specific for particular CXR stages. Comparison of PPs between CXR stage I patients with or without Löfgren's syndrome revealed 25 differentially expressed peaks. The total number of deregulated peaks and also of those associated with sarcoidosis as a whole were markedly lower in patients with Löfgren's syndrome in comparison with other sarcoid phenotypes. Human serum albumin, alpha1-antitrypsin, and protocadherin-2 precursor were identified from sarcoidosis-associated PP.
Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy enables determination of protein patterns in sarcoid BALF and allows detection of protein patterns linked to a particular disease course.
肺结节病是一种具有多种临床表型的多系统肉芽肿性疾病。到目前为止,关于结节病患者支气管肺泡灌洗液(BALF)的蛋白质图谱(PPs)的信息很少,且尚无临床疾病亚型PPs的数据。
研究肺结节病患者BALF的PP,评估PPs是否反映胸部X线(CXR)评估的疾病进程,并比较有/无 Löfgren 综合征患者的PPs。
应用表面增强激光解吸/电离飞行时间质谱法研究65例患者(CXR I期,n = 32;CXR II期,n = 22;CXR III期,n = 11)和23名健康对照者未浓缩BALF中的PPs。采用 Mann-Whitney U检验检测差异表达的蛋白峰。经过反相分级分离后,使用肽指纹图谱和免疫去除法鉴定失调(上调或下调)的蛋白质。
与对照者相比,在肺结节病患者中检测到40个差异表达的蛋白质实体(2.75 - 185.62 kD)(p < 0.05)。虽然13个峰(33%)在所有CXR阶段均存在,但27个(67%)峰特定于特定的CXR阶段。比较CXR I期有/无Löfgren综合征患者的PPs,发现25个差异表达峰。与其他结节病表型相比,Löfgren综合征患者中失调峰的总数以及与整个结节病相关的峰的总数明显更低。从结节病相关的PP中鉴定出人血清白蛋白、α1-抗胰蛋白酶和原钙黏蛋白-2前体。
表面增强激光解吸/电离飞行时间质谱法能够确定结节病BALF中的蛋白质图谱,并能够检测与特定疾病进程相关的蛋白质图谱。