Rath Timo, Zwaschka Lisa, Hage Lisa, Kügler Marion, Menendez Katrin, Naehrlich Lutz, Schulz Richard, Roderfeld Martin, Roeb Elke
Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany; Friedrich Alexander University Erlangen, Department of Medicine 1, Erlangen, Germany.
Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
PLoS One. 2014 Dec 29;9(12):e115847. doi: 10.1371/journal.pone.0115847. eCollection 2014.
Cystic Fibrosis (CF) lung disease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lung disease and the occurrence of pulmonary exacerbations (PEx) are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lung disease.
54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lung disease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001.
Adults and children with moderate to severe CF lung disease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency.
MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lung disease and PEx.
囊性纤维化（CF）肺部疾病的特征是肺功能逐渐下降，是导致CF相关高发病率和死亡率的主要因素。然而，除了肺活量测定法外，仍缺乏可靠指示CF肺部疾病和肺部加重（PEx）发生的呼吸系统疾病替代标志物。在本研究中，我们旨在识别用于检测CF肺部疾病的新实验生物标志物。
54名成年CF患者和26名儿科CF患者纳入本研究，通过酶联免疫吸附测定法（ELISA）对血清中基质金属蛋白酶-1、-2、-8、-9、-13、组织金属蛋白酶抑制剂-1、-2、YKL-40、透明质酸、前胶原III肽的浓度进行定量。通过肺功能测试诊断CF肺部疾病，根据Rosenfeld在2001年建立的临床评分定义PEx。
患有中度至重度CF肺部疾病的成人和儿童血清中基质金属蛋白酶-8、-9、YKL-40和组织金属蛋白酶抑制剂-1的表达显著增加。此外，与无呼吸加重临床体征的成年CF患者相比，患有PEx的成年CF患者中基质金属蛋白酶-8、-9和YKL-40显著增加。基质金属蛋白酶-8、-9、YKL-40和组织金属蛋白酶抑制剂-1的血清水平不受CF肝病或胰腺功能不全的影响。
基质金属蛋白酶-8、-9和YKL-40可能作为CF肺部疾病和PEx的新型非侵入性生物标志物。
