Role of HMGB1 as a Suitable Biomarker of Subclinical Intestinal Inflammation and Mucosal Healing in Patients with Inflammatory Bowel Disease
Role of HMGB1 as a Suitable Biomarker of Subclinical Intestinal Inflammation and Mucosal Healing in Patients with Inflammatory Bowel Disease
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DOI：
10.1097/mib.0000000000000113
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发表时间：
2014-08-01
影响因子：
4.9
通讯作者：
Stronati, Laura
中科院分区：
文献类型：
--
作者：
Palone, Francesca;Vitali, Roberta;Stronati, Laura
背景资料：目前缺乏炎症性肠病患者的高级别和低级别肠道炎症以及粘膜愈合（MH）的非侵入性生物标志物。我们最近发现，粪便高迁移率族蛋白1（HMGB 1）蛋白是肠道炎症的一种新的生物标志物。我们的目的是在小鼠模型中研究HMGB 1是否能够预测临床上明显的和亚临床的肠道炎症，以及其正常化是否指示MH。我们的目的也是在确认结果与克罗恩病（CD）和溃疡性colis.Methods：C57 BL 6/J小鼠用葡聚糖硫酸钠剂量增加，以诱导不同严重程度的结肠炎，28 CD，23溃疡性结肠炎，17对照组也入组。结果：在葡聚糖硫酸钠剂量为0.25%、0.50%、1%和4%时，粪便HMGB 1分别增加5倍、11倍、18倍和24倍，表明该蛋白检测到高度炎症和亚临床炎症。治疗后4周恢复时间后，HMGB 1恢复至对照水平，与MH平行。在患者中，粪便HMGB 1显着相关的内镜指数（克罗恩病[SES-CD]，内镜马约亚评分），但不与疾病活动指数（克罗恩病活动指数，部分马约score）。结论：粪便HMGB 1是一个强大的非侵入性生物标志物的临床明显和亚临床肠道炎症，它也可以是一个替代标志物的MH。我们建议使用粪便HMGB 1监测炎症性肠病的病程和评估治疗结果。
Background: Noninvasive biomarkers of high- and low-grade intestinal inflammation and of mucosal healing (MH) in patients with inflammatory bowel disease are currently lacking. We have recently shown that fecal high mobility group box 1 (HMGB1) protein is a novel biomarker of gut inflammation. We aimed at investigating in a mouse model if HMGB1 was able to foresee both a clinically evident and a subclinical gut inflammation and if its normalization indicated MH. We also aimed at confirming the results in patients with Crohn's disease (CD) and ulcerative colitis.Methods: C57BL6/J mice were treated with increasing doses of dextran sodium sulphate to induce colitis of different severity degrees; 28 with CD, 23 with ulcerative colitis, and 17 controls were also enrolled. Fecal HMGB1 was analyzed by enzyme-linked immunosorbent assay and immunoblotting.Results: Fecal HMGB1 increased by 5-, 11-, 18-, and 24-folds with dextran sodium sulphate doses of 0.25%, 0.50%, 1%, and 4%, respectively, showing that the protein detected a high- grade and a subclinical inflammation. After a recovery time of 4-week posttreatment, HMGB1 returned to control levels, paralleling MH. In patients, fecal HMGB1 significantly correlated with endoscopic indexes (Simple Endoscopic Score for Crohn's Disease [SES-CD], endoscopic Mayo subscore), but not with the disease activity indexes (Crohn's disease Activity Index, partial Mayo score).Conclusions: Fecal HMGB1 is a robust noninvasive biomarker of clinically overt and subclinical gut inflammation; it can also be a surrogate marker of MH. We suggest the use of fecal HMGB1 to monitor the disease course and assess therapy outcomes in inflammatory bowel disease.