Zaidi Deenaz, Bording-Jorgensen Michael, Huynh Hien Q, Carroll Matthew W, Turcotte Jean-Francois, Sergi Consolato, Liu Julia, Wine Eytan
*Department of Pediatrics †Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR) ‡Department of Physiology §Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada ||University of Arkansas for Medical Sciences, Little Rock, AR.
J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):644-650. doi: 10.1097/MPG.0000000000001182.
Inflammatory bowel diseases (IBD) present commonly in childhood, with unknown etiology, but an important role for the epithelial lining is suggested. Epithelial cell extrusion, measured by counting gaps between epithelial cells, is higher in adult patients with Crohn disease (CD) than in controls. Our objectives were to compare epithelial gaps in the duodenum of IBD and non-IBD pediatric patients, to study the correlation between epithelial gaps, inflammation, and disease activity, and identify potential mechanisms.
Epithelial gap density of the duodenum was evaluated using probe-based confocal laser endomicroscopy in 26 pediatric patients with IBD (16 CD, 10 ulcerative colitis [UC]) and 17 non-IBD controls during endoscopy. Epithelial gaps were correlated with serum inflammatory markers, disease activity indices, and intraepithelial lymphocytes. A panel of 10 inflammatory cytokines and expression of TNFAIP3 (A20; inhibits NF-κβ-induced inflammation) were analyzed in duodenal and ileal biopsies.
Confocal imaging showed significantly higher epithelial gap density in patients with IBD, including UC. Interleukin (IL)-2 and IL-8 were higher in duodenal but not ileal biopsies of patients with UC. No significant correlation was present between C-reactive protein, erythrocyte sedimentation rate, disease activity indices, and epithelial gaps in patients with UC. In patients with CD, C-reactive protein positively correlated with epithelial gaps. A20 expression in the duodenum was unchanged among non-IBD and IBD cases.
Duodenal epithelial gaps are increased in pediatric patients with IBD (including UC) but are unrelated to inflammation. This suggests that altered epithelial barrier is an important systemic feature of pediatric IBD and is not only secondary to inflammation.
炎症性肠病（IBD）在儿童期较为常见，病因不明，但提示上皮细胞层起着重要作用。通过计算上皮细胞之间的间隙来测量的上皮细胞挤出，在成年克罗恩病（CD）患者中高于对照组。我们的目的是比较IBD和非IBD儿科患者十二指肠中的上皮间隙，研究上皮间隙、炎症和疾病活动之间的相关性，并确定潜在机制。
在内镜检查期间，使用基于探头的共聚焦激光内镜显微镜对26例IBD儿科患者（16例CD，10例溃疡性结肠炎[UC]）和17例非IBD对照患者的十二指肠上皮间隙密度进行评估。上皮间隙与血清炎症标志物、疾病活动指数和上皮内淋巴细胞相关。对十二指肠和回肠活检组织分析了一组10种炎性细胞因子以及TNFAIP3（A20；抑制NF-κβ诱导的炎症）的表达。
共聚焦成像显示，包括UC患者在内的IBD患者上皮间隙密度显著更高。UC患者十二指肠活检组织中白细胞介素（IL）-2和IL-8水平较高，但回肠活检组织中无此现象。UC患者的C反应蛋白、红细胞沉降率、疾病活动指数与上皮间隙之间无显著相关性。在CD患者中，C反应蛋白与上皮间隙呈正相关。非IBD和IBD病例十二指肠中A20的表达无变化。
IBD（包括UC）儿科患者的十二指肠上皮间隙增加，但与炎症无关。这表明上皮屏障改变是儿科IBD的一个重要全身特征，并非仅是炎症的继发表现。
