Leach Steven T, Yang Zheng, Messina Isabella, Song Changjie, Geczy Carolyn L, Cunningham Anne M, Day Andrew S
School of Women's and Children's Health, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Scand J Gastroenterol. 2007 Nov;42(11):1321-31. doi: 10.1080/00365520701416709.
Various markers characterize the complex inflammatory processes seen in chronic inflammatory bowel disease (IBD) including calprotectin, a complex of two S100 proteins, which has been evaluated and validated as a faecal marker of inflammation. However, the systemic and mucosal expression patterns of calprotectin and related S100 proteins are not well characterized in this disease. The objective of this study was to assess serum and mucosal levels of calprotectin, S100A12 and soluble receptor for advanced glycation end products (sRAGE), a putative S100 ligand, in a paediatric population with IBD.
Children were enrolled at diagnosis of IBD, along with groups of children without IBD. Standard inflammatory markers and disease activity scores were collated. Calprotectin, S100A12 and sRAGE levels in serum and biopsy culture supernatants were measured by ELISA and tissue distribution of S100 proteins was investigated by immunohistochemistry.
Serum and mucosal calprotectin and S100A12 levels were increased in children with IBD as compared with non-IBD controls. Serum calprotectin levels correlated with S100A12 levels and with disease activity scores in children with IBD. sRAGE levels were not increased in IBD. S100A8, S100A9 and S100A12 were abundantly expressed throughout the lamina propria and epithelium in inflamed mucosa. In contrast, these proteins were present in the lamina propria, but not the epithelium, in non-inflamed mucosa.
Serum calprotectin and S100A12 are increased in children with IBD and indicate disease activity. Elevated levels of these proteins are present in the colonic mucosa and may contribute to the pathogenesis of IBD. Furthermore, an imbalance between sRAGE and S100A12 may contribute to inflammatory changes present in IBD.
多种标志物可表征慢性炎症性肠病(IBD)中所见的复杂炎症过程,包括钙卫蛋白,它是由两种S100蛋白组成的复合物,已作为炎症的粪便标志物进行评估和验证。然而,钙卫蛋白及相关S100蛋白的全身和黏膜表达模式在该疾病中尚未得到充分表征。本研究的目的是评估IBD患儿血清和黏膜中钙卫蛋白、S100A12以及晚期糖基化终末产物可溶性受体(sRAGE,一种假定的S100配体)的水平。
在IBD诊断时纳入患儿,并设立无IBD的儿童组。整理标准炎症标志物和疾病活动评分。采用酶联免疫吸附测定(ELISA)法检测血清及活检培养上清液中钙卫蛋白、S100A12和sRAGE水平,并通过免疫组织化学研究S100蛋白的组织分布。
与非IBD对照组相比,IBD患儿血清和黏膜中的钙卫蛋白及S100A12水平升高。IBD患儿血清钙卫蛋白水平与S100A12水平以及疾病活动评分相关。IBD患儿的sRAGE水平未升高。S100A8、S100A9和S100A12在炎症黏膜的固有层和上皮中大量表达。相比之下,在非炎症黏膜中,这些蛋白存在于固有层,但不存在于上皮中。
IBD患儿血清中的钙卫蛋白和S100A12升高,提示疾病活动。这些蛋白在结肠黏膜中水平升高,可能有助于IBD的发病机制。此外,sRAGE与S100A12之间的失衡可能导致IBD中出现的炎症变化。