Thorsvik Silje, Damås Jan Kristian, Granlund Atle vB, Flo Trude Helen, Bergh Kåre, Østvik Ann Elisabet, Sandvik Arne Kristian
Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Gastroenterology, St. Olav's University Hospital, Trondheim, Norway.
J Gastroenterol Hepatol. 2017 Jan;32(1):128-135. doi: 10.1111/jgh.13598.
Accurate, noninvasive biomarkers are needed to diagnose and monitor inflammatory bowel disease (IBD). Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin 2, is expressed in inflamed colonic epithelium and neutrophilic granulocytes. This study explores its properties as a biomarker in feces and plasma and, for the first time, compares fecal NGAL systematically with the existing fecal biomarker calprotectin.
Neutrophil gelatinase-associated lipocalin was measured in feces from 73 patients with IBD, 21 patients with infectious enterocolitis, 21 patients with irritable bowel syndrome, and 23 healthy subjects using ELISA. The results were correlated to calprotectin, clinical score, endoscopic score, and high-sensitive C-reactive protein. Plasma from 119 patients with IBD and 28 healthy controls was analyzed for NGAL.
Fecal NGAL levels (median and interquartile range) were significantly elevated in active ulcerative colitis (UC) 6.05 (3.6-15.1) mg/kg and Crohn's disease (CD) 4.9 (1.5-7.7) mg/kg, compared with patients with inactive UC 1.3 (0.4-2.6) mg/kg, inactive CD 1.5 (0.5-1.7) mg/kg, irritable bowel syndrome 0.4 (0.2-0.6) mg/kg, and healthy controls (HC) 0.3 (0.1-0.4) mg/kg. Patients with infectious enterocolitis had significantly higher fecal-NGAL levels, 2.7 (1.4-5.6) mg/kg than HC. Sensitivity and specificity was 94.7% and 95.7%, respectively, for distinguishing between active IBD and HC. Stability of NGAL in stool was excellent for 7 days in room temperature. Plasma NGAL was significantly elevated in UC and CD compared with HC.
Fecal NGAL is a promising biomarker for IBD. As existing biomarkers are expressed mainly in granulocytes, NGAL's epithelial localization may give supplementary diagnostic information.
诊断和监测炎症性肠病(IBD)需要准确的非侵入性生物标志物。中性粒细胞明胶酶相关脂质运载蛋白(NGAL),也称为脂质运载蛋白2,在炎症性结肠上皮和中性粒细胞中表达。本研究探讨其作为粪便和血浆中生物标志物的特性,并首次将粪便NGAL与现有的粪便生物标志物钙卫蛋白进行系统比较。
使用酶联免疫吸附测定法(ELISA)测量73例IBD患者、21例感染性小肠结肠炎患者、21例肠易激综合征患者和23名健康受试者粪便中的中性粒细胞明胶酶相关脂质运载蛋白。结果与钙卫蛋白、临床评分、内镜评分和高敏C反应蛋白相关。分析119例IBD患者和28名健康对照者血浆中的NGAL。
与非活动期溃疡性结肠炎(UC)患者1.3(0.4 - 2.6)mg/kg、非活动期克罗恩病(CD)患者1.5(0.5 - 1.7)mg/kg、肠易激综合征患者0.4(0.2 - 0.6)mg/kg以及健康对照者(HC)0.3(0.1 - 0.4)mg/kg相比,活动期溃疡性结肠炎(UC)患者粪便NGAL水平(中位数和四分位间距)显著升高,为6.05(3.6 - 15.1)mg/kg,克罗恩病(CD)患者为4.9(1.5 - 7.7)mg/kg。感染性小肠结肠炎患者粪便NGAL水平显著高于健康对照者,为2.7(1.4 - 5.6)mg/kg。区分活动期IBD和健康对照者时,敏感性和特异性分别为94.7%和95.7%。NGAL在粪便中于室温下7天内稳定性极佳。与健康对照者相比,UC和CD患者血浆NGAL显著升高。
粪便NGAL是一种有前景的IBD生物标志物。由于现有生物标志物主要在粒细胞中表达,NGAL的上皮定位可能提供补充诊断信息。