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Role of HMGB1 as a Suitable Biomarker of Subclinical Intestinal Inflammation and Mucosal Healing in Patients with Inflammatory Bowel Disease

Palone, Francesca PhD*; Vitali, Roberta PhD*; Cucchiara, Salvatore MD, PhD; Pierdomenico, Maria PhD*; Negroni, Anna PhD*; Aloi, Marina MD; Nuti, Federica MD; Felice, Carla MD; Armuzzi, Alessandro MD; Stronati, Laura PhD*

doi: 10.1097/MIB.0000000000000113
Original Basic Research Articles

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.

Article first published online 30 June 2014.

*Department of Radiobiology and Human Health, ENEA, Rome, Italy;

Department of Pediatrics and Infantile Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; and

IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.

Reprints: Laura Stronati, PhD, Department of Radiobiology and Human Health, ENEA, CR Casaccia, Via Anguillarese 301, 00123 Rome, Italy (e-mail:

Supported in part by the Grant RBAP104JYK_002 from Ministry of Education, University and Research (MIUR) and by the DMG Italia Srl.

The authors have no conflicts of interest to disclose.

Received April 02, 2014

Accepted May 14, 2014

© Crohn's & Colitis Foundation of America, Inc.
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