Institute for Liver and Digestive Health, University College of London, London, UK.
Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
United European Gastroenterol J. 2021 Mar;9(2):268-278. doi: 10.1177/2050640620977371. Epub 2021 Mar 29.
Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis.
We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included.
In the acute and chronic dextran sulphate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05).
PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.
在炎症性肠病中,肠道上皮屏障受损的情况非常严重。连接上皮细胞和细胞外基质的跨膜胶原蛋白在维持上皮细胞稳态方面起着重要作用。因此,我们试图确定跨膜型 23 胶原蛋白是否可以作为克罗恩病和溃疡性结肠炎患者疾病活动的替代标志物。
我们开发了一种酶联免疫吸附试验来检测血清中的 23 型胶原蛋白的胞外结构域(PRO-C23),随后评估其在大鼠急性和慢性葡聚糖硫酸钠结肠炎模型以及人类炎症性肠病队列中的水平。纳入了 44 名克罗恩病和 29 名溃疡性结肠炎患者的血清,这些患者的疾病处于活动期和非活动期。
在急性和慢性葡聚糖硫酸钠诱导的大鼠结肠炎模型中,结肠炎后 PRO-C23 血清水平显著升高,疾病缓解后恢复正常水平。与健康供体相比,处于活动期的克罗恩病(p<0.05)和溃疡性结肠炎(p<0.001)患者的血清 PRO-C23 水平升高。PRO-C23 可将健康供体与溃疡性结肠炎(曲线下面积 [AUC]:0.81,p=0.0009)和克罗恩病(AUC:0.70,p=0.0124)区分开来。PRO-C23 可将活动期溃疡性结肠炎患者与缓解期患者(AUC:0.75,p=0.0219)以及活动期克罗恩病患者与缓解期患者(AUC:0.68,p=0.05)区分开来。
在活动性结肠炎的大鼠和活动性疾病的炎症性肠病患者中,PRO-C23 的水平升高。因此,PRO-C23 可作为监测溃疡性结肠炎和克罗恩病疾病活动的替代标志物。