Ciccocioppo Rachele, Imbesi Venerina, Betti Elena, Boccaccio Vincenzo, Kruzliak Peter, Gallia Alessandra, Cangemi Giuseppina Cristina, Maffe Gabriella Carnevale, Vanoli Alessandro, Merante Serena, De Amici Mara, Falcone Colomba, Klersy Catherine, Corazza Gino Roberto
Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy,
Dig Dis Sci. 2015 Aug;60(8):2327-37. doi: 10.1007/s10620-015-3619-7. Epub 2015 Mar 11.
RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity.
We enrolled 60 CD, 67 UC patients, and 66 controls (all adults). Disease activity was scored through the clinical, endoscopic, and histologic indexes of severity, whilst disease location and behaviour were assessed according to the Montreal classification. In all cases, the levels of serum sRAGE, S100A12, C-reactive protein, and faecal calprotectin were measured.
sRAGE levels were significantly lower in UC, both active and inactive, than in controls and CD (817.35, range 437.3-1449; 1211, range 843.7-1618; 1207.5, range 743.15-1875.75; P < 0.05 for both), and inversely correlated with clinical and endoscopic indexes of activity in both IBD groups (P < 0.05 for all) and with the histologic score in the CD group. Moreover, those CD patients with a penetrating behaviour showed a significant reduction in both sRAGE (P = 0.006) and S100A12 (P = 0.034) as compared to those with an inflammatory/stricturing pattern. Although S100A12 levels were not found up-regulated, a negative correlation appeared evident with the clinical (r = -0.38) and endoscopic (r = -0.32) indexes of activity in UC and CD, respectively.
These data suggest a different role for RAGE in CD and UC, and a potential use of sRAGE as a new biomarker.
RAGE是一种在免疫细胞和内皮细胞上表达的跨膜受体，它与其配体S100钙粒蛋白结合会导致慢性炎症。相反，其可溶性形式（sRAGE）通过充当诱饵发挥保护作用。我们对克罗恩病（CD）和溃疡性结肠炎（UC）患者的血清sRAGE和S100A12水平进行了横断面分析，并寻找其与临床和生物学活性标志物之间的相关性。
我们纳入了60例CD患者、67例UC患者和66例对照者（均为成年人）。通过临床、内镜和组织学严重程度指标对疾病活动进行评分，同时根据蒙特利尔分类法评估疾病部位和行为。在所有病例中，均测量了血清sRAGE、S100A12、C反应蛋白和粪便钙卫蛋白的水平。
UC患者（无论活动期还是非活动期）的sRAGE水平均显著低于对照组和CD患者（分别为817.35，范围437.3 - 1449；1211，范围843.7 - 1618；1207.5，范围743.15 - 1875.75；两者P均<0.05），并且在两个炎症性肠病（IBD）组中均与临床和内镜活动指标呈负相关（所有P均<0.05），在CD组中与组织学评分呈负相关。此外，与具有炎症/狭窄型的CD患者相比，具有穿透性病变行为的CD患者的sRAGE（P = 0.006）和S100A12（P = 0.034）均显著降低。虽然未发现S100A12水平上调，但分别在UC和CD中与临床（r = -0.38）和内镜（r = -0.32）活动指标呈明显负相关。
这些数据表明RAGE在CD和UC中发挥不同作用，并且sRAGE有作为一种新生物标志物的潜在用途。
